Preimplantation Genetic Testing for Aneuploidy Improves Cumulative Live Birth Rate and Reduces Miscarriage in Recurrent Pregnancy Loss

Preimplantation Genetic Testing for Aneuploidy Improves Cumulative Live Birth Rate and Reduces Miscarriage in Recurrent Pregnancy Loss | 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 Preimplantation Genetic Testing for Aneuploidy Improves Cumulative Live Birth Rate and Reduces Miscarriage in Recurrent Pregnancy Loss Luping Yu, Na Kong, Jingyu Liu, Fangfang He, Ningyuan Zhang, Jie Mei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6399928/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 Objective To evaluate whether preimplantation genetic testing for aneuploidy to deselect aneuploid embryos improves cumulative live birth rate and reduces miscarriage risk in normal karyotype couples with recurrent pregnancy loss undergoing assisted reproductive technology. Design: Retrospective cohort study. Subjects: A total of 1,039 couples with recurrent pregnancy loss who underwent assisted reproductive treatment between January 2013 and December 2023. Exposure: Patients were stratified into two groups based on their decision to undergo preimplantation genetic testing for aneuploidy. Results Among women with recurrent pregnancy loss, preimplantation genetic testing for aneuploidy increased the cumulative live birth rate to 70% compared to 51% in women ≤ 35 years (adjusted risk ratio, 1.38; 95% confidence interval, 1.05–1.82; P = 0.025) and to 35% compared to 21% in women > 35 years (adjusted risk ratio, 1.69; 95% confidence interval, 1.03–2.77; P = 0.037). Preimplantation genetic testing reduced the early miscarriage rate to 7% vs. 13%, ( P = 0.030) and the late miscarriage rate to 0% vs. 3% ( P = 0.016) in women ≤ 35 years. Subgroup analysis revealed that the significant benefit of preimplantation genetic testing diminished in patients undergoing fresh embryo transfers. Conclusion Preimplantation genetic testing for aneuploidy significantly increased the cumulative live birth rate in couples with recurrent pregnancy loss across both age groups (≤ 35 years and > 35 years) and reduced early and late miscarriage rates in those ≤ 35 years. However, its benefits diminished in patients undergoing fresh embryo transfers, suggesting that the embryo transfer strategy may influence its effectiveness. Recurrent pregnancy loss preimplantation genetic testing for aneuploidy cumulative live birth rate miscarriage Figures Figure 1 Introduction Pregnancy loss is a distressing complication affecting 15–25% of pregnant women, with approximately 80% of cases occurring in the first trimester. Furthermore, a smaller percentage of women (1–5%) experience a more serious condition known as recurrent pregnancy loss (RPL), which is defined as the loss of two or more consecutive or non-consecutive pregnancies, including biochemical pregnancies and pregnancies of unknown location. According to the guidelines of the Practice Committee of the American Society for Reproductive Medicine (ASRM) (PCotASfR, 2020 ) and the European Society of Human Reproduction and Embryology (ESHRE) (Bender Atik, et al., 2023 ).RPL has both physical and psychological implications. Beyond risks such as infection and hemorrhage, affected individuals often experience significant psychological distress. Established causes of RPL include parental chromosomal abnormalities (e.g., balanced translocations) (Franssen, et al., 2005 ), uterine anomalies (Sugiura-Ogasawara, et al., 2010 ), endocrine disorders (Dong, et al., 2020 ), and autoimmune factors (Bramham, et al., 2010 ). Despite advancements in understanding RPL, more than half of cases remain unexplained when products of conception (POC) have not undergone karyotyping (Bender, et al., 2023, PCotASfR, 2020 ), while de novo aneuploidy is believed to account for 40–50% of the cause when the POC have been analyzed (Kutteh, et al., 2024 , Popescu, et al., 2018 ).Given that chromosomal abnormalities account for the majority of early miscarriages, preimplantation genetic testing for aneuploidy (PGT-A) has emerged as a potential strategy to improve pregnancy outcomes and reduce miscarriage rates in women with RPL. Advancements in molecular methodologies, including array comparative genomic hybridization (aCGH), digital polymerase chain reaction (dPCR), single-nucleotide polymorphism (SNP) arrays, real-time quantitative PCR (qPCR), and next-generation sequencing (NGS), have significantly enhanced the accuracy and efficiency of PGT-A. Trophectoderm (TE) biopsy at the blastocyst stage, combined with comprehensive chromosome screening (CCS), outperforms cleavage-stage biopsy by overcoming limitations such as incomplete chromosomal analysis and reduced live birth rates. This strategy not only preserves implantation potential but also allows sufficient time for genetic assessment through vitrification of biopsied blastocysts, thereby facilitating more precise selection of euploid embryos and improving clinical outcomes (Sui, et al., 2020 ). PGT-A is widely employed to reduce miscarriage rates by selecting euploid embryos, thereby minimizing pregnancy loss due to aneuploidy. Studies suggested that PGT-A may enhance the live birth rate following the first embryo transfer in women of advanced maternal age (AMA) (Greco, et al., 2020 , Rubio, et al., 2017 , Sacchi, et al., 2019 ). However, its efficacy in RPL remains a subject of ongoing debate. Bhatt et al. (Bhatt, et al., 2021 ) analyzed the largest available dataset and reported that PGT-A improves outcomes in patients with RPL, a finding consistent with a meta-analysis (Mumusoglu, et al., 2025 ). Notably, their study defined RPL as three or more pregnancy losses. In contrast, other studies (Mastenbroek, et al., 2011 ) have demonstrated limited efficacy for this approach. A meta-analysis of nine randomized controlled trials (RCTs) revealed that PGT-A not only failed to improve but also adversely affected the live birth rate in women of AMA. Furthermore, recent trials have shown that PGT-A did not increase ongoing pregnancy or live birth rates in women under 35 years of age (Munné, et al., 2019 , Ozgur, et al., 2019 ). However, these studies focused on pregnancy outcomes following the first embryo transfer rather than the cumulative live birth rate per oocyte retrieval cycle, which is considered the most important patient-centered outcome for IVF success (Wilkinson, et al., 2017 ). Given these conflicting findings, this study aims to evaluate pregnancy outcomes, with the primary outcome being the cumulative live birth rate. Secondary outcomes include the live birth rate, clinical pregnancy rate, early miscarriage rate, and late miscarriage rate in women with RPL undergoing IVF, with or without PGT-A. These findings are critical for clinicians managing RPL and for patients experiencing recurrent pregnancy loss (Daar, et al., 2017 ). Materials and Method Study Design We conducted a retrospective cohort study by searching the database of the Reproductive Medicine Center, Nanjing Drum Tower Hospital to identify infertile women with a medical history of RPL who underwent IVF between January 2013 and December 2023. The study included couples with two or more failed clinical pregnancies between 6 and 24 weeks of gestation, primarily between 6 and 12 weeks, excluding ectopic, molar, or biochemical pregnancies (according to the ASRM guidelines). Exclusion criteria included chromosomal abnormalities in either partner, anatomical abnormalities (e.g., uterine malformations such as unicornuate uterus and duplex uterus, untreated septate uterus, adenomyoma, submucosal uterine fibroids, or endometrial polyps), hypothyroidism, thrombophilia, antiphospholipid antibody syndrome (APS), and other severe comorbidities to ensure that the study focused on RPL cases without confounding factors. A total of 1,039 couples with RPL (200 who underwent PGT-A and 839 who did not) met the inclusion criteria and were included in the study. Outcome data were available for all participants. Patient cycles were identified using consistent identification codes and organized by the date of oocyte retrieval and embryo transfer. This study was approved by the Ethics Committee (Approval No.: 2021-384-01). Ovarian stimulation, Oocyte retrieval, Embryo culture, and PGT-A Patients underwent controlled ovarian stimulation (COS), oocyte retrieval, and embryo transfer (ET) following standard protocols, selected based on physician discretion and individualized according to patient characteristics, including age and ovarian reserve, as estimated by serum anti-Müllerian hormone (AMH) and/or basal follicle-stimulating hormone (FSH) levels. Ovarian stimulation was conducted using either long or short protocols with gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, or clomiphene citrate (CC) (Sawada, et al., 2018 ). Oocyte maturation was triggered with 5,000 IU of human chorionic gonadotropin (hCG) when the leading follicle exceeded 20 mm in diameter, as measured by transvaginal ultrasonography. Oocyte retrieval was performed 36 hours post-hCG administration under ultrasound guidance. In the PGT-A group, intracytoplasmic sperm injection (ICSI) was used for fertilization. Normal fertilization was confirmed by the presence of two polar bodies (2PB) and two pronuclei (2PN) at 16–18 hours post-insemination. Fertilized embryos were cultured under controlled conditions at 37°C in an atmosphere of 5% O₂ and 6% CO₂ using a sequential culture medium (G1/G2; Vitrolife, Sweden). Embryos that arrested in development or exhibited > 50% fragmentation by day 3 were discarded, while the remaining embryos were cultured to the blastocyst stage. Blastocysts were evaluated according to the Gardner criteria (Gardner, et al., 2000 ), and trophectoderm (TE) biopsies were performed on day 5 or 6 for blastocysts with a morphological score of 4BC or higher using laser technology. Biopsied TE cells underwent whole-genome amplification using the PicoPLEX WGA kit (Takara, Japan), followed by chromosomal ploidy analysis via next-generation sequencing (NGS) on the Illumina platform, with a resolution of 10 Mb. After biopsy, blastocysts were vitrified using the Kitazato Vitrification Kit (Kitazato, Tokyo, Japan). In the non-PGT-A group, either conventional in vitro fertilization (IVF) or ICSI was performed, depending on the presence or absence of male factor infertility. Embryos were either transferred fresh (1–2 embryos) on day 3 or day 5/6, or underwent frozen embryo transfer (FET) in subsequent cycles. Clinical outcome and Statistical analysis The primary outcome was the cumulative live birth rate that resulted from up to three embryo transfers performed, including all COS cycles. Secondary outcomes included the clinical pregnancy rate, live birth rate, early miscarriage rate, and late miscarriage rate per embryo transfer (ET). Biochemical pregnancy was defined as a positive serum hCG (> 100 mIU/mL) on day 14 post-ET without ultrasound evidence of a gestational sac. Clinical pregnancy was confirmed by the detection of a gestational sac and fetal heartbeat via transvaginal ultrasonography at 4 and 6 weeks after transfer (approximately 7 and 9 weeks of gestation). Early miscarriage was defined as the loss of a previously detected fetal heartbeat before 12 weeks of gestation, whereas late miscarriage was defined as the loss of an intrauterine clinical pregnancy between 12 and 28 weeks of gestation. For twin pregnancies, both monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) pregnancies were considered as a single pregnancy cycle. Continuous variables were presented as mean ± standard deviation (SD) or median (range), while categorical variables were expressed as n (%). The Student’s t -test or the Mann–Whitney U-test was used for parametric and non-parametric continuous variables, respectively. The Chi-squared test or Fisher’s exact test was applied to categorical variables, as appropriate. Generalized estimating equations (GEE) logistic regression models accounted for multiple cycles per patient and were used to assess differences. Covariates included in the model were age, body mass index (BMI), FSH level, antral follicle count (AFC), number of pregnancy losses, duration of infertility, number of embryos transferred, and the use of PGT-A (indication, test method). Covariates significantly associated with outcome measures ( P < 0.05) were retained in the final adjusted models. Given the significant effect of maternal age on embryo euploidy (Cimadomo, et al., 2021 ), patients were stratified into two groups based on age: ≤ 35 years (younger patients) and > 35 years (advanced maternal age, AMA), and analyzed separately for PGT-A and Non‑PGT-A groups. All statistical analyses were performed using SPSS software (Version 21; IBM Corporation, NY, USA), with a two-sided P -value < 0.05 considered statistically significant. Result Baseline Characteristics of RPL Patients A total of 1,039 couples met the inclusion criteria described in the Materials and Methods, comprising 200 women, 230 COS cycles, and 262 FET cycles in the PGT-A group, as well as 839 women, 1,192 COS cycles, 507 fresh ET cycles, and 766 FET cycles in the non-PGT-A group. Data for these cycles were retrospectively analyzed for this study [Table 1 ]. No significant differences were observed between the PGT-A and non‑PGT-A groups in terms of maternal age, paternal age, maternal BMI, number of pregnancy losses, basal reproductive hormone levels (including FSH, luteinizing hormone [LH], prolactin [PRL], estradiol [E 2 ], testosterone [T]), and AFC. However, the duration of infertility was significantly longer in the non‑PGT-A group. Table 1 Baseline characteristics of PGT‑A and non-PGT-A groups. PGT‑A group Non‑PGT-A group P Number of infertile couples (n) 200 839 Maternal age (year, x̅ ± SD) 33.73 ± 4.56 34.05 ± 5.17 0.409 Paternal age (year, x̅ ± SD) 34.69 ± 5.05 35.50 ± 6.04 0.055 Maternal BMI (kg/m 2 , x̅ ± SD) 22.62 ± 2.73 23.35 ± 7.13 0.086 Duration of infertility years (year, median ± IQR) 1.00 [1.00, 2.00] 2.00 [1.00, 3.00] < 0.001 Pregnancy loss (n, median ± IQR) 2.00 [2.00, 3.00] 2.00 [2.00, 3.00] 0.172 Female reproductive endocrine hormonesa a FSH (mIU/mL, x̅ ± SD) 7.50 ± 3.40 7.84 ± 3.16 0.165 LH (mIU/mL, x̅ ± SD) 5.19 ± 2.65 5.27 ± 3.43 0.689 PRL (ng/mL, x̅ ± SD) 25.59 ± 42.64 29.62 ± 68.91 0.307 E 2 (pg/mL, x̅ ± SD) 49.00 ± 71.74 50.68 ± 88.65 0.781 T(ng/dL, x̅ ± SD) 0.68 ± 3.20 1.02 ± 6.10 0.282 AFC (n, x̅ ± SD) ) 15.78 ± 9.62 14.59 ± 8.05 0.068 PGT-A: Preimplantation genetic testing for aneuploidy; BMI: Body mass index; a Menstrual day 3–5 basal endocrine hormones; FSH: Follicle‑stimulating hormone; LH: Luteinizing hormone; PRL: Prolactin; E 2 : Estradiol; T: Testosterone; AFC: Antral Follicle Count; SD: Standard deviation; IQR: Interquartile range. Characteristics of the Two Groups in Ovarian Stimulation and Embryo Development The PGT-A group underwent a total of 230 COS cycles. Among them, 177 (88.50%) patients underwent COS once, 17 (8.50%) twice, and 5 (2.50%) and 1 (0.50%) undergoing COS three and four times, respectively. In comparison, the non‑PGT-A group underwent 1,192 COS cycles, with 623 (74.26%) undergoing COS once, 141 (16.81%) twice, and 42 (5.01%), 16 (1.91%), and 17 (2.03%) undergoing COS three, four, and five or more times, respectively [Table 2 ]. The duration of gonadotropin administration and total gonadotropin dosage were comparable between the two groups [Table 2 ]. The PGT-A group had significantly higher numbers of retrieved oocytes, MII oocytes, fertilized oocytes, and maximum estrogen levels on the day of hCG administration compared to the non‑PGT-A group [Table 2 ]. However, the number of euploid embryos available for transfer after PGT-A testing was significantly lower in the PGT-A group (3.09 ± 1.68 vs. 5.44 ± 3.02, P < 0.001). Endometrial thickness was comparable between the groups. In the PGT-A group, all patients underwent single blastocyst transfer, whereas in the non‑PGT-A group, 558 cycles (43.83%) were single embryo transfers, and 416 cycles (32.68%) were blastocyst transfers [Table 2 ]. Table 2 COS, oocyte retrieval, and embryo development of PGT‑A and non-PGT-A groups. PGT‑A group Non‑PGT-A group P Number of COS cycles (n) 230 1,192 Number of infertile couples (n) 200 839 Number of COS cycles for patients, n (%) 1 177 (88.50) 623 (74.26) < 0.001 2 17 (8.50) 141 (16.81) < 0.001 3 5 (2.50) 42 (5.01) < 0.001 4 1 (0.50) 16 (1.91) < 0.001 ≥5 0 17 (2.03) < 0.001 Gonadotropin days (x̅ ± SD) 9.66 ± 3.07 10.03 ± 3.66 0.069 Gonadotropin dosage (IU, x̅ ± SD) 1,994.28 ± 840.86 1,923.11 ± 942.43 0.192 Maximum estrogen level on day of hCG (pg/mL, x̅ ± SD) 3,594.35 ± 2556.38 2,737.88 ± 2233.20 < 0.001 Retrieval oocytes (n, x̅ ± SD) 13.85 ± 6.67 9.60 ± 6.15 < 0.001 MII oocytes (n, x̅ ± SD) 8.57 ± 6.66 7.34 ± 5.70 0.003 Normal fertilized Oocytes (n, x̅ ± SD) 7.34 ± 5.92 6.14 ± 4.97 0.001 Embryos available for transfer (n,x̅ ± SD) 3.09 ± 1.68 5.44 ± 3.02 < 0.001 Endometrial thickness (mm, x̅ ± SD) 8.73 ± 1.62 9.00 ± 2.91 0.582 Number of embryos transferred, n (%) < 0.001 Single 262 (100.00) 558 (43.83) Double 0 (0.00) 715 (56.17) Stage of embryos transferred, n (%) < 0.001 Day 3 0 (0.00) 857 (67.32) Day 5/6 262 (100.00) 416 (32.68) COS: Controlled ovarian stimulation; aneuploidy; hCG: Human chorionic gonadotrophin; MII: Metaphase II. Cumulative Live Birth Rate was Higher in the PGT-A group The PGT-A group underwent 230 COS cycles, while the non-PGT-A group underwent 1,192 COS cycles. Given the significant impact of maternal age on embryo euploidy (Cimadomo, Capalbo, Dovere, Tacconi, Soscia, Giancani, Scepi, Maggiulli, Vaiarelli, Rienzi and Ubaldi, 2021) and the need to adjust for covariates, patients were stratified into two age groups: ≤35 years and > 35 years. Among women diagnosed with RPL, the application of PGT-A was significantly associated with an increased cumulative live birth rate (CLBR), at 58% vs. 38% (a RR : 1.52, 95% CI [1.19–1.93], P = 0.001), regardless of age [Table 3 ]. Stratified by age, CLBR was 70% vs. 51% (a RR : 1.38, 95% CI [1.05–1.82], P = 0.025) for women ≤ 35 years and 35% vs. 21% (a RR : 1.69, 95% CI [1.03–2.77], P = 0.037) for those > 35 years. Furthermore, the multiple pregnancy rate was significantly lower in the PGT-A group, decreasing from 12–3% (a RR : 0.22, 95% CI [0.08–0.62], P = 0.002) among patients ≤ 35 years. Among those > 35 years, the multiple pregnancy rate was 0% vs. 4% ( P = 0.155) [Table 3 ]. Secondary outcomes, including live birth rate (LBR), clinical pregnancy rate, early miscarriage rate, and late miscarriage rate per embryo transfer (ET), for the PGT-A and non-PGT-A groups are presented in Table 4 . The adjusted risk ratios (a RR ) comparing the PGT-A and non-PGT-A groups are shown, with subgroup analyses based on fresh embryo transfer or FET for pregnancy outcomes presented in Fig. 1 . Notably, the results indicated that the application of PGT-A significantly increased the LBR, from 36–51% (a RR : 1.42, 95% CI [1.13–1.80], P = 0.003), regardless of age. In women > 35 years, the LBR increased from 22–41% (a RR : 1.90, 95% CI [1.14–3.15], P = 0.012). Furthermore, both the early and late miscarriage rates were significantly reduced with PGT-A. The early miscarriage rate decreased from 13–7% ( P = 0.030), and the late miscarriage rate decreased from 3–0% ( P = 0.016) in patients ≤ 35 years. When compared with the non-PGT-A FET subgroup, PGT-A significantly increased the LBR, from 31–51% (a RR : 1.65, 95% CI [1.28–2.13], P = 0.001), regardless of age. In women > 35 years, the LBR increased from 17–41% (a RR : 2.38, 95% CI [1.39–4.06], P = 0.001). Furthermore, in patients ≤ 35 years, PGT-A reduced the miscarriage rate. The early miscarriage rate decreased from 15–7% ( P = 0.014), and the late miscarriage rate decreased from 3–0% ( P = 0.022). Additionally, when subgroup analysis was performed for non-PGT-A fresh embryo transfer, PGT-A reduced the late miscarriage rate, from 3–0% ( P = 0.013) in patients ≤ 35 years. Table 3 Comparison of cumulative live birth rate between PGT-A and non-PGT-A groups. PGT‑A group Non‑PGT-A group P a RR (95% CI) Number of COS cycles (n) 230 1,192 Cumulative live birth rate (%) Total 134/230 (58.26%) 458/1,192 (38.42%) 0.001 1.52 (1.19, 1.93) Age ≤ 35 108/155 (69.68%) 359/710 (50.56%) 0.025 1.38 (1.05, 1.82) Singleton 104/155 (67.10%) 277/710 (39.01%) 35 26/75 (34.67%) 99/482 (20.54%) 0.037 1.69 (1.03, 2.77) Singleton 26/75 (34.67%) 80/482 (16.60%) 0.016 2.09 (1.26, 3.46) Twin 0/75 (0.00%) 19/482 (3.94%) 0.155 0.00 COS: Controlled ovarian stimulation; a RR : adjusted risk ratio. Table 4 Comparison of clinical outcomes between PGT‑A and non-PGT-A groups. PGT‑A group Non‑PGT-A group Non‑PGT-A Fresh ET Non‑PGT-A Frozen ET Number of ET cycles (n) 262 1273 507 766 Clinical pregnancy rate (%) Total 155/262 (59.16%) 677/1273 (53.18%) 303/507 (59.76%) 374/766 (48.83%) ≤35 124/199 (62.31%) 507/818 (61.98%) 247/392 (63.01%) 260/426 (61.03%) >35 31/63 (49.21%) 170/455 (37.36%) 56/115 (48.70%) 114/340 (33.53%) Live birth rate (%) Total 134/262 (51.15%) 458/1273 (35.98%) 221/507 (43.59%) 237/766 (30.94%) ≤35 108/199 (54.27%) 359/818 (43.89%) 181/392 (46.17%) 178/426 (41.78%) >35 26/63 (41.27%) 99/455 (21.76%) 40/115 (34.78%) 59/340 (17.35%) Early miscarriage rate (≤ 12w) (%) Total 17/262 (6.49%) 163/1273 (12.80%) 57/507 (11.24%) 106/766 (13.84%) ≤35 14/199 (7.04%) 108/818 (13.20%) 45/392 (11.48%) 63/426 (14.79%) >35 3/63 (4.76%) 55/455 (12.09%) 12/115 (10.43%) 43/340 (12.65%) Late miscarriage rate (>12w) (%) Total 0/262 (0.00%) 33/1273 (2.59%) 15/507 (2.96%) 18/766 (2.35%) ≤35 0/199 (0.00%) 25/818 (3.06%) 13/392 (3.32%) 12/426 (2.82%) >35 0/63 (0.00%) 8/455 (1.76%) 2/115 (1.74%) 6/340 (1.76%) ET: Embryo transfer. Discussion Our study results demonstrate a significant increase in cumulative live birth rate and a notable reduction in both early and late miscarriage rates with the use of PGT-A in women with recurrent pregnancy loss, consistent with previous reports (Bhatt, Marchetto, Roy, Morelli and McGovern, 2021 , Mumusoglu, Telek and Ata, 2025 ). Additionally, we observed an increased LBR when comparing non-PGT-A FET subgroup, but no significant difference was found when comparing non-PGT-A fresh embryo transfer. Our study is the first to analyze fresh embryo transfer and FET as subgroups. In general, fresh embryo transfer is performed in patients with favorable pregnancy prognoses, who typically exhibit a good ovarian response, an adequate number of retrieved oocytes, and multiple high-quality embryos available for transfer. These findings underscore the importance of the cumulative live birth rate as the primary endpoint in clinical trials. According to the recommendations of the ASRM, there is insufficient evidence to support the routine use of PGT-A in all couples with infertility. Previous studies have reported that among women with a good prognosis for live birth, conventional IVF achieves a cumulative live birth rate that is noninferior to that of PGT-A, regardless of maternal age (≤ 35 years or > 35 years) (Yan, et al., 2021 ). In our study, we demonstrate that, for patients with RPL, who may have a less favorable prognosis, PGT-A significantly improves cumulative live birth rates, regardless of maternal age (≤ 35 years or > 35 years). Additionally, although the number of embryos transferred per cycle was lower in the PGT-A group, this led to a significant reduction in the multiple pregnancy rate. The transfer of multiple embryos increases the incidence of multiple pregnancies, highlighting the associated risks. The PGT-A approach, which involves transferring a single euploid embryo, not only reduced miscarriage rate but also minimized the occurrence of multiple pregnancies. The theoretical benefit of PGT-A lies in its ability to screen embryos for chromosomal abnormalities prior to implantation. Several studies have investigated the relationship between euploidy rates and various factors, including patients’ reproductive history, PGT-A diagnoses, and implantation outcomes following euploid blastocyst transfer. However, maternal age at the time of oocyte retrieval has consistently been identified as the only significant factor influencing mean euploidy rates per biopsied blastocyst. Previous findings have demonstrated no significant association between euploidy rates and factors such as prior live births, miscarriages, failed in IVF cycles, or implantation failures (Cimadomo, Capalbo, Dovere, Tacconi, Soscia, Giancani, Scepi, Maggiulli, Vaiarelli, Rienzi and Ubaldi, 2021). Recent evidence, however, suggests a significantly higher incidence of chromosomal abnormalities in blastocysts from younger patients (≤ 35 years) with idiopathic recurrent pregnancy loss (iRPL) (48.9%) compared to those with no or sporadic clinical miscarriages (36.9%), while no significant difference has been observed in blastocysts from patients over 35 years (Liu, et al., 2020 ). Chen et al. (Yan, Qin, Zhao, Sun, Gong, Li, Sun, Ling, Li, Hao, Tan, Yang, Zhu, Liu, Chen, Wei, Lu, Ni, Zhou, Wu, Gao, Shi, Lu, Zhang, Wu, Ma, Ma, Fu, Zhang, Meng, Zhang, Legro and Chen, 2021) reported that among women aged 20 to 37 years, the proportion of euploid embryos was 1,262 out of 1,809 (69.8%). In our center, the proportion of euploid embryos in women with RPL under 35 years of age was 58.4%. These findings indicate a significantly higher prevalence of chromosomal abnormalities in blastocysts from younger patients (≤ 35 years) with RPL compared to those with no or sporadic clinical miscarriages. Accordingly, the greater improvement in pregnancy outcomes observed in patients under 35 years is likely attributable to the reduction in aneuploid miscarriages associated with the use of PGT-A. Our findings support the implantation checkpoint hypothesis (PCotASfR, 2012 ), which suggests that, for optimal reproductive success, the endometrium at the time of implantation must be both receptive and selective. An endometrium that is excessively receptive but insufficiently selective may lead to rapid conceptions but also to a high incidence of early pregnancy losses due to abnormalities in the implanting embryo. The primary objective of PGT-A is to facilitate the birth of a healthy child while reducing the burden of implantation failures and miscarriages (Sermon, et al., 2016 ). Compared to the expected clinical miscarriage rate of 15–25% (PCotASfR, 2012 ), our study demonstrated a significantly lower early miscarriage rate in the PGT-A group (6% overall, 7% for patients ≤ 35 years, and 4% for those > 35 years). Consistent with previous studies, our findings confirm a reduced incidence of early pregnancy loss in the PGT-A group, regardless of maternal age (Rubio, et al., 2017 , Verpoest, et al., 2018 , Yan, et al., 2021 ). These results suggest that PGT-A improves embryo selection, thereby increasing the likelihood of embryos progressing beyond the first trimester. It is important to note that our trial has several limitations. One limitation is its retrospective design, which inherently relies on pre-existing data and may introduce selection bias. Additionally, the study population is restricted to women with RPL undergoing IVF, potentially for indications beyond RPL, and does not encompass all RPL patients who may not require IVF. The PGT-A plus FET strategy employed in the PGT-A group presents a potential source of bias in the analysis of pregnancy outcomes, as the non-PGT-A group included both fresh and frozen-thawed transfers at the cleavage and blastocyst stages. Prior evidence suggests that blastocyst transfer yields higher implantation and live birth rates, which likely influenced the observed outcomes between the two groups (Glujovsky, et al., 2022 ). Moreover, it is essential to highlight that, compared to fresh embryo transfers without PGT-A, the application of PGT-A does not confer any improvement in pregnancy outcomes. Furthermore, the genetic testing platform used for PGT-A, whether aCGH or NGS, was not specified in the dataset. This omission prevents any assessment of potential variations in outcomes based on the testing methodology. Additionally, it remains uncertain whether PGT-A improves pregnancy and live birth rates in these patients beyond its baseline utility. Furthermore, for patients with RPL without infertility—who would not otherwise pursue IVF—it is uncertain whether IVF for PGT-A is a worthwhile investment of time and resources. Moreover, the PGT-A strategy typically involves the use of FET, which studies suggest may increase the risk of maternal hypertensive disorders, as well as the likelihood of delivering a large-for-gestational-age baby and higher birth weight (Zaat, et al., 2021 ). Ideally, one or more fetal aneuploidies diagnosed in previous POC should warrant further evaluation. However, the current rate of aneuploidy diagnosis in POC remains relatively low. Conclusions In conclusion, despite these limitations, our study provides compelling evidence supporting the use of PGT-A in women experiencing RPL. The findings demonstrate that the selection of euploid embryos through PGT-A for FET significantly improves the cumulative live birth rate compared to the use of untested embryos. This evidence can assist clinicians in guiding personalized treatment strategies for this challenging condition. However, the effectiveness of PGT-A for the treatment of RPL, particularly in individuals undergoing fresh embryo transfer, remains inconclusive.Furthermore, large, well-designed randomized controlled trials (RCTs) are needed to further clarify the benefits of PGT-A in improving cumulative live birth rate and reducing miscarriage risk among couples with unexplained RPL. Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Nanjing Drum Tower Hospital (Approval No.: 2021-384-01). Written informed consent was obtained from all participants prior to enrollment. Consent for publication Not applicable. Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests None. Funding This work was supported by the National Natural Science Foundation of China (Grant No. 82301891 to Y.L.P) and the National Natural Science Foundation of China (Grant No. 82371678 to M.J). Authors’ contributions Y.L.P participated in study design, analysis, manuscript drafting, and critical discussion. K.N, L.J.Y, H.F.F, and Z.N.Y participated in study analysis, execution, statistical analysis, and critical discussion. M.J participated in study design, execution, statistical analysis, manuscript drafting, and critical discussion. All authors read and approved the final manuscript. Acknowledgements We appreciate all the members of the Reproductive Medicine Center, Nanjing Drum Tower Hospital for providing the clinical information database. References Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Mcheik S, Peramo B, Quenby S. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Human reproduction open 2023;2023: hoad002. Bhatt SJ, Marchetto NM, Roy J, Morelli SS, McGovern PG. Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study. Human reproduction (Oxford, England) 2021;36: 2339-2344. Bramham K, Hunt B, Germain S, Calatayud I, Khamashta M, Bewley S, Nelson-Piercy C. Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus 2010;19: 58-64. Cimadomo D, Capalbo A, Dovere L, Tacconi L, Soscia D, Giancani A, Scepi E, Maggiulli R, Vaiarelli A, Rienzi L et al. Leave the past behind: women's reproductive history shows no association with blastocysts' euploidy and limited association with live birth rates after euploid embryo transfers. Human reproduction (Oxford, England) 2021;36: 929-940. Daar J, Benward J, Collins L, Davis J, Francis L, Gates E, Ginsburg E, Klipstein S, Koenig B, La Barbera A. Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion. Fertility and sterility 2017;107: 1130-1135. Dong AC, Morgan J, Kane M, Stagnaro-Green A, Stephenson MD. Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis. Fertility and sterility 2020;113: 587-600. e581. Franssen MT, Korevaar JC, Leschot NJ, Bossuyt PM, Knegt AC, Gerssen-Schoorl KB, Wouters CH, Hansson KB, Hochstenbach R, Madan K. Selective chromosome analysis in couples with two or more miscarriages: case-control study. bmj 2005;331: 137-141. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertility and sterility 2000;73: 1155-1158. Glujovsky D, Retamar AMQ, Sedo CRA, Ciapponi A, Cornelisse S, Blake D. Cleavage‐stage versus blastocyst‐stage embryo transfer in assisted reproductive technology. Cochrane database of systematic reviews 2022. Greco E, Litwicka K, Minasi MG, Cursio E, Greco PF, Barillari P. Preimplantation genetic testing: where we are today. International journal of molecular sciences 2020;21: 4381. Kutteh WH, Papas RS, Maisenbacher MK, Dahdouh EM. Role of genetic analysis of products of conception and PGT in managing early pregnancy loss. Reproductive BioMedicine Online 2024;49: 103738. Liu X-Y, Fan Q, Wang J, Li R, Xu Y, Guo J, Wang Y-Z, Zeng Y-H, Ding C-H, Cai B. Higher chromosomal abnormality rate in blastocysts from young patients with idiopathic recurrent pregnancy loss. Fertility and sterility 2020;113: 853-864. Mastenbroek S, Twisk M, Van Der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Human reproduction update 2011;17: 454-466. Mumusoglu S, Telek SB, Ata B. Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis. Fertility and sterility 2025;123: 121-136. Munné S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertility and sterility 2019;112: 1071-1079. e1077. Ozgur K, Berkkanoglu M, Bulut H, Yoruk GDA, Candurmaz NN, Coetzee K. Single best euploid versus single best unknown-ploidy blastocyst frozen embryo transfers: a randomized controlled trial. Journal of Assisted Reproduction and Genetics 2019;36: 629-636. PCotASfR M. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertility and sterility 2012;98: 1103-1111. PCotASfR M. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertility and sterility 2020;113: 533-535. Popescu F, Jaslow C, Kutteh W. Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients. Human Reproduction 2018;33: 579-587. Rubio C, Bellver J, Rodrigo L, Castillón G, Guillén A, Vidal C, Giles J, Ferrando M, Cabanillas S, Remohí J. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertility and sterility 2017;107: 1122-1129. Sacchi L, Albani E, Cesana A, Smeraldi A, Parini V, Fabiani M, Poli M, Capalbo A, Levi-Setti PE. Preimplantation genetic testing for aneuploidy improves clinical, gestational, and neonatal outcomes in advanced maternal age patients without compromising cumulative live-birth rate. Journal of assisted reproduction and genetics 2019;36: 2493-2504. Sawada Y, Sato T, Saito C, Ozawa F, Ozaki Y, Sugiura-Ogasawara M. Clinical utility of decorin in follicular fluid as a biomarker of oocyte potential. Reproductive Biology 2018;18: 33-39. Sermon K, Capalbo A, Cohen J, Coonen E, De Rycke M, De Vos A, Delhanty J, Fiorentino F, Gleicher N, Griesinger G. The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. MHR: Basic science of reproductive medicine 2016;22: 845-857. Sugiura-Ogasawara M, Ozaki Y, Kitaori T, Kumagai K, Suzuki S. Midline uterine defect size is correlated with miscarriage of euploid embryos in recurrent cases. Fertility and sterility 2010;93: 1983-1988. Sui Y-L, Lei C-X, Ye J-F, Fu J, Zhang S, Li L, Peng X-D, Zhang Y-P, Chen G-W, Sun X-X. In vitro fertilization with single-nucleotide polymorphism microarray-based preimplantation genetic testing for aneuploidy significantly improves clinical outcomes in infertile women with recurrent pregnancy loss: a randomized controlled trial. Reproductive and Developmental Medicine 2020;4: 32-41. Verpoest W, Staessen C, Bossuyt PM, Goossens V, Altarescu G, Bonduelle M, Devesa M, Eldar-Geva T, Gianaroli L, Griesinger G. Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial. Human reproduction 2018;33: 1767-1776. Wilkinson J, Roberts SA, Vail A. Developments in IVF warrant the adoption of new performance indicators for ART clinics, but do not justify the abandonment of patient-centred measures. Human Reproduction 2017;32: 1155-1159. Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, Sun X, Ling X, Li H, Hao C et al. Live Birth with or without Preimplantation Genetic Testing for Aneuploidy. N Engl J Med 2021;385: 2047-2058. Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database of Systematic Reviews 2021. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6399928","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":451603716,"identity":"fce490ec-6be7-4e86-9cc0-830cff8e3fc7","order_by":0,"name":"Luping Yu","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Luping","middleName":"","lastName":"Yu","suffix":""},{"id":451603717,"identity":"b7159f2e-762e-4da3-901f-3979e70dc235","order_by":1,"name":"Na Kong","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Kong","suffix":""},{"id":451603718,"identity":"e50bd892-740b-44c3-b61e-eb4c89d010f3","order_by":2,"name":"Jingyu Liu","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Jingyu","middleName":"","lastName":"Liu","suffix":""},{"id":451603720,"identity":"0d42a335-5ef8-4916-8bbe-d7a2fb73d89f","order_by":3,"name":"Fangfang He","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Fangfang","middleName":"","lastName":"He","suffix":""},{"id":451603723,"identity":"a7c586c4-3a4c-4ec1-a65a-f5fb543affe5","order_by":4,"name":"Ningyuan Zhang","email":"","orcid":"","institution":"Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Ningyuan","middleName":"","lastName":"Zhang","suffix":""},{"id":451603724,"identity":"c844f762-24d0-4e0d-89bf-a0ccb90abb23","order_by":5,"name":"Jie Mei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYFACxgaDBIZ/cmzsjY0PP5Cg5YAxP8/hZmMJEqw6kCg5I71NgIcYtbrtzQ0FDyruJBjcfNjGIMFgJ6fbQECL2ZmDQIedeZZncDux7UEBQ7Kx2QFCWm4kNhgktjEXA7W0G0gAXbiNoJb7D4Fa/jEnbrh5sE2ChygtN4AhlthwOHHmDEZitZwBOizhWBowkBOBgWxAjF+OH39m+KPGBhiVxx8+/FBhJ0dQCxCwGSDYBriVIQPmB8SpGwWjYBSMghELAD+YSjn6bT4rAAAAAElFTkSuQmCC","orcid":"","institution":"Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","correspondingAuthor":true,"prefix":"","firstName":"Jie","middleName":"","lastName":"Mei","suffix":""}],"badges":[],"createdAt":"2025-04-08 06:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6399928/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6399928/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82299688,"identity":"5f9e8f40-4059-445c-b394-a22013478429","added_by":"auto","created_at":"2025-05-08 20:37:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4283094,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of women with recurrent pregnancy loss (RPL) who underwent PGT-A versus those who did not, with subgroup analysis based on fresh embryo transfer and frozen embryo transfer (FET), stratified by age groups. Among women with RPL, the use of PGT-A was associated with increased live birth rate and reduced early and late miscarriage rates. Data are presented as adjusted risk ratios (a\u003cem\u003eRR\u003c/em\u003e). The dotted line represents a risk ratio of 1.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6399928/v1/51b14cb67b823b5e2605213e.png"},{"id":92850477,"identity":"fc490142-d0ef-4bcb-b17f-e9ece3e58ffc","added_by":"auto","created_at":"2025-10-06 10:38:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7274089,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6399928/v1/dc37e313-7197-4496-b3f7-6a55fb7e1397.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePreimplantation Genetic Testing for Aneuploidy Improves Cumulative Live Birth Rate and Reduces Miscarriage in Recurrent Pregnancy Loss\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePregnancy loss is a distressing complication affecting 15\u0026ndash;25% of pregnant women, with approximately 80% of cases occurring in the first trimester. Furthermore, a smaller percentage of women (1\u0026ndash;5%) experience a more serious condition known as recurrent pregnancy loss (RPL), which is defined as the loss of two or more consecutive or non-consecutive pregnancies, including biochemical pregnancies and pregnancies of unknown location. According to the guidelines of the Practice Committee of the American Society for Reproductive Medicine (ASRM) (PCotASfR, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and the European Society of Human Reproduction and Embryology (ESHRE) (Bender Atik, et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).RPL has both physical and psychological implications. Beyond risks such as infection and hemorrhage, affected individuals often experience significant psychological distress. Established causes of RPL include parental chromosomal abnormalities (e.g., balanced translocations) (Franssen, et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2005\u003c/span\u003e), uterine anomalies (Sugiura-Ogasawara, et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2010\u003c/span\u003e), endocrine disorders (Dong, et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), and autoimmune factors (Bramham, et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). Despite advancements in understanding RPL, more than half of cases remain unexplained when products of conception (POC) have not undergone karyotyping (Bender, et al., 2023, PCotASfR, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), while de novo aneuploidy is believed to account for 40\u0026ndash;50% of the cause when the POC have been analyzed (Kutteh, et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2024\u003c/span\u003e, Popescu, et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).Given that chromosomal abnormalities account for the majority of early miscarriages, preimplantation genetic testing for aneuploidy (PGT-A) has emerged as a potential strategy to improve pregnancy outcomes and reduce miscarriage rates in women with RPL. Advancements in molecular methodologies, including array comparative genomic hybridization (aCGH), digital polymerase chain reaction (dPCR), single-nucleotide polymorphism (SNP) arrays, real-time quantitative PCR (qPCR), and next-generation sequencing (NGS), have significantly enhanced the accuracy and efficiency of PGT-A. Trophectoderm (TE) biopsy at the blastocyst stage, combined with comprehensive chromosome screening (CCS), outperforms cleavage-stage biopsy by overcoming limitations such as incomplete chromosomal analysis and reduced live birth rates. This strategy not only preserves implantation potential but also allows sufficient time for genetic assessment through vitrification of biopsied blastocysts, thereby facilitating more precise selection of euploid embryos and improving clinical outcomes (Sui, et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePGT-A is widely employed to reduce miscarriage rates by selecting euploid embryos, thereby minimizing pregnancy loss due to aneuploidy. Studies suggested that PGT-A may enhance the live birth rate following the first embryo transfer in women of advanced maternal age (AMA) (Greco, et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2020\u003c/span\u003e, Rubio, et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2017\u003c/span\u003e, Sacchi, et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). However, its efficacy in RPL remains a subject of ongoing debate. Bhatt et al. (Bhatt, et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) analyzed the largest available dataset and reported that PGT-A improves outcomes in patients with RPL, a finding consistent with a meta-analysis (Mumusoglu, et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Notably, their study defined RPL as three or more pregnancy losses. In contrast, other studies (Mastenbroek, et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2011\u003c/span\u003e) have demonstrated limited efficacy for this approach. A meta-analysis of nine randomized controlled trials (RCTs) revealed that PGT-A not only failed to improve but also adversely affected the live birth rate in women of AMA. Furthermore, recent trials have shown that PGT-A did not increase ongoing pregnancy or live birth rates in women under 35 years of age (Munn\u0026eacute;, et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e, Ozgur, et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). However, these studies focused on pregnancy outcomes following the first embryo transfer rather than the cumulative live birth rate per oocyte retrieval cycle, which is considered the most important patient-centered outcome for IVF success (Wilkinson, et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven these conflicting findings, this study aims to evaluate pregnancy outcomes, with the primary outcome being the cumulative live birth rate. Secondary outcomes include the live birth rate, clinical pregnancy rate, early miscarriage rate, and late miscarriage rate in women with RPL undergoing IVF, with or without PGT-A. These findings are critical for clinicians managing RPL and for patients experiencing recurrent pregnancy loss (Daar, et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e"},{"header":"Materials and Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study by searching the database of the Reproductive Medicine Center, Nanjing Drum Tower Hospital to identify infertile women with a medical history of RPL who underwent IVF between January 2013 and December 2023. The study included couples with two or more failed clinical pregnancies between 6 and 24 weeks of gestation, primarily between 6 and 12 weeks, excluding ectopic, molar, or biochemical pregnancies (according to the ASRM guidelines). Exclusion criteria included chromosomal abnormalities in either partner, anatomical abnormalities (e.g., uterine malformations such as unicornuate uterus and duplex uterus, untreated septate uterus, adenomyoma, submucosal uterine fibroids, or endometrial polyps), hypothyroidism, thrombophilia, antiphospholipid antibody syndrome (APS), and other severe comorbidities to ensure that the study focused on RPL cases without confounding factors. A total of 1,039 couples with RPL (200 who underwent PGT-A and 839 who did not) met the inclusion criteria and were included in the study. Outcome data were available for all participants. Patient cycles were identified using consistent identification codes and organized by the date of oocyte retrieval and embryo transfer. This study was approved by the Ethics Committee (Approval No.: 2021-384-01).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOvarian stimulation, Oocyte retrieval, Embryo culture, and PGT-A\u003c/h3\u003e\n\u003cp\u003ePatients underwent controlled ovarian stimulation (COS), oocyte retrieval, and embryo transfer (ET) following standard protocols, selected based on physician discretion and individualized according to patient characteristics, including age and ovarian reserve, as estimated by serum anti-M\u0026uuml;llerian hormone (AMH) and/or basal follicle-stimulating hormone (FSH) levels. Ovarian stimulation was conducted using either long or short protocols with gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, or clomiphene citrate (CC) (Sawada, et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Oocyte maturation was triggered with 5,000 IU of human chorionic gonadotropin (hCG) when the leading follicle exceeded 20 mm in diameter, as measured by transvaginal ultrasonography. Oocyte retrieval was performed 36 hours post-hCG administration under ultrasound guidance.\u003c/p\u003e \u003cp\u003eIn the PGT-A group, intracytoplasmic sperm injection (ICSI) was used for fertilization. Normal fertilization was confirmed by the presence of two polar bodies (2PB) and two pronuclei (2PN) at 16\u0026ndash;18 hours post-insemination. Fertilized embryos were cultured under controlled conditions at 37\u0026deg;C in an atmosphere of 5% O₂ and 6% CO₂ using a sequential culture medium (G1/G2; Vitrolife, Sweden). Embryos that arrested in development or exhibited\u0026thinsp;\u0026gt;\u0026thinsp;50% fragmentation by day 3 were discarded, while the remaining embryos were cultured to the blastocyst stage. Blastocysts were evaluated according to the Gardner criteria (Gardner, et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2000\u003c/span\u003e), and trophectoderm (TE) biopsies were performed on day 5 or 6 for blastocysts with a morphological score of 4BC or higher using laser technology. Biopsied TE cells underwent whole-genome amplification using the PicoPLEX WGA kit (Takara, Japan), followed by chromosomal ploidy analysis via next-generation sequencing (NGS) on the Illumina platform, with a resolution of 10 Mb. After biopsy, blastocysts were vitrified using the Kitazato Vitrification Kit (Kitazato, Tokyo, Japan). In the non-PGT-A group, either conventional in vitro fertilization (IVF) or ICSI was performed, depending on the presence or absence of male factor infertility. Embryos were either transferred fresh (1\u0026ndash;2 embryos) on day 3 or day 5/6, or underwent frozen embryo transfer (FET) in subsequent cycles.\u003c/p\u003e\n\u003ch3\u003eClinical outcome and Statistical analysis\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the cumulative live birth rate that resulted from up to three embryo\u003c/p\u003e \u003cp\u003etransfers performed, including all COS cycles. Secondary outcomes included the clinical pregnancy rate, live birth rate, early miscarriage rate, and late miscarriage rate per embryo transfer (ET). Biochemical pregnancy was defined as a positive serum hCG (\u0026gt;\u0026thinsp;100 mIU/mL) on day 14 post-ET without ultrasound evidence of a gestational sac. Clinical pregnancy was confirmed by the detection of a gestational sac and fetal heartbeat via transvaginal ultrasonography at 4 and 6 weeks after transfer (approximately 7 and 9 weeks of gestation). Early miscarriage was defined as the loss of a previously detected fetal heartbeat before 12 weeks of gestation, whereas late miscarriage was defined as the loss of an intrauterine clinical pregnancy between 12 and 28 weeks of gestation. For twin pregnancies, both monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) pregnancies were considered as a single pregnancy cycle.\u003c/p\u003e \u003cp\u003eContinuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (range), while categorical variables were expressed as n (%). The Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test or the Mann\u0026ndash;Whitney U-test was used for parametric and non-parametric continuous variables, respectively. The Chi-squared test or Fisher\u0026rsquo;s exact test was applied to categorical variables, as appropriate. Generalized estimating equations (GEE) logistic regression models accounted for multiple cycles per patient and were used to assess differences. Covariates included in the model were age, body mass index (BMI), FSH level, antral follicle count (AFC), number of pregnancy losses, duration of infertility, number of embryos transferred, and the use of PGT-A (indication, test method). Covariates significantly associated with outcome measures (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were retained in the final adjusted models. Given the significant effect of maternal age on embryo euploidy (Cimadomo, et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), patients were stratified into two groups based on age: \u0026le; 35 years (younger patients) and \u0026gt;\u0026thinsp;35 years (advanced maternal age, AMA), and analyzed separately for PGT-A and Non‑PGT-A groups. All statistical analyses were performed using SPSS software (Version 21; IBM Corporation, NY, USA), with a two-sided \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Characteristics of RPL Patients\u003c/h2\u003e \u003cp\u003eA total of 1,039 couples met the inclusion criteria described in the Materials and Methods, comprising 200 women, 230 COS cycles, and 262 FET cycles in the PGT-A group, as well as 839 women, 1,192 COS cycles, 507 fresh ET cycles, and 766 FET cycles in the non-PGT-A group. Data for these cycles were retrospectively analyzed for this study [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. No significant differences were observed between the PGT-A and non‑PGT-A groups in terms of maternal age, paternal age, maternal BMI, number of pregnancy losses, basal reproductive hormone levels (including FSH, luteinizing hormone [LH], prolactin [PRL], estradiol [E\u003csub\u003e2\u003c/sub\u003e], testosterone [T]), and AFC. However, the duration of infertility was significantly longer in the non‑PGT-A group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of PGT‑A and non-PGT-A groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePGT‑A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon‑PGT-A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of infertile couples (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age (year, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.73\u0026thinsp;\u0026plusmn;\u0026thinsp;4.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.05\u0026thinsp;\u0026plusmn;\u0026thinsp;5.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.409\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaternal age (year, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.69\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.50\u0026thinsp;\u0026plusmn;\u0026thinsp;6.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal BMI (kg/m\u003csup\u003e2\u003c/sup\u003e, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.35\u0026thinsp;\u0026plusmn;\u0026thinsp;7.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of infertility years\u003c/p\u003e \u003cp\u003e(year, median\u0026thinsp;\u0026plusmn;\u0026thinsp;IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00 [1.00, 2.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 [1.00, 3.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy loss (n, median\u0026thinsp;\u0026plusmn;\u0026thinsp;IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.00 [2.00, 3.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 [2.00, 3.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eFemale reproductive endocrine hormonesa\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH (mIU/mL, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH (mIU/mL, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.27\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.689\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRL (ng/mL, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.59\u0026thinsp;\u0026plusmn;\u0026thinsp;42.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.62\u0026thinsp;\u0026plusmn;\u0026thinsp;68.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE\u003csub\u003e2\u003c/sub\u003e (pg/mL, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.00\u0026thinsp;\u0026plusmn;\u0026thinsp;71.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.68\u0026thinsp;\u0026plusmn;\u0026thinsp;88.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT(ng/dL, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.68\u0026thinsp;\u0026plusmn;\u0026thinsp;3.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.282\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFC (n, x̅ \u0026plusmn; SD) )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.78\u0026thinsp;\u0026plusmn;\u0026thinsp;9.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.59\u0026thinsp;\u0026plusmn;\u0026thinsp;8.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePGT-A: Preimplantation genetic testing for aneuploidy; BMI: Body mass index; \u003csup\u003ea\u003c/sup\u003eMenstrual day 3\u0026ndash;5 basal endocrine hormones; FSH: Follicle‑stimulating hormone; LH: Luteinizing hormone; PRL: Prolactin; E\u003csub\u003e2\u003c/sub\u003e: Estradiol; T: Testosterone; AFC: Antral Follicle Count; SD: Standard deviation; IQR: Interquartile range.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the Two Groups in Ovarian Stimulation and Embryo Development\u003c/h2\u003e \u003cp\u003eThe PGT-A group underwent a total of 230 COS cycles. Among them, 177 (88.50%) patients underwent COS once, 17 (8.50%) twice, and 5 (2.50%) and 1 (0.50%) undergoing COS three and four times, respectively. In comparison, the non‑PGT-A group underwent 1,192 COS cycles, with 623 (74.26%) undergoing COS once, 141 (16.81%) twice, and 42 (5.01%), 16 (1.91%), and 17 (2.03%) undergoing COS three, four, and five or more times, respectively [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. The duration of gonadotropin administration and total gonadotropin dosage were comparable between the two groups [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. The PGT-A group had significantly higher numbers of retrieved oocytes, MII oocytes, fertilized oocytes, and maximum estrogen levels on the day of hCG administration compared to the non‑PGT-A group [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. However, the number of euploid embryos available for transfer after PGT-A testing was significantly lower in the PGT-A group (3.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68 vs. 5.44\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Endometrial thickness was comparable between the groups. In the PGT-A group, all patients underwent single blastocyst transfer, whereas in the non‑PGT-A group, 558 cycles (43.83%) were single embryo transfers, and 416 cycles (32.68%) were blastocyst transfers [Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCOS, oocyte retrieval, and embryo development of PGT‑A and non-PGT-A groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePGT‑A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon‑PGT-A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of COS cycles (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of infertile couples (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eNumber of COS cycles for patients, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e177 (88.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e623 (74.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (8.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e141 (16.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (5.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin days (x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;3.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin dosage (IU, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,994.28\u0026thinsp;\u0026plusmn;\u0026thinsp;840.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,923.11\u0026thinsp;\u0026plusmn;\u0026thinsp;942.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.192\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum estrogen level on day of hCG\u003c/p\u003e \u003cp\u003e(pg/mL, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,594.35\u0026thinsp;\u0026plusmn;\u0026thinsp;2556.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,737.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2233.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetrieval oocytes (n, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.85\u0026thinsp;\u0026plusmn;\u0026thinsp;6.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.60\u0026thinsp;\u0026plusmn;\u0026thinsp;6.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMII oocytes (n, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.57\u0026thinsp;\u0026plusmn;\u0026thinsp;6.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.34\u0026thinsp;\u0026plusmn;\u0026thinsp;5.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal fertilized Oocytes (n, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.34\u0026thinsp;\u0026plusmn;\u0026thinsp;5.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbryos available for transfer (n,x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.44\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrial thickness (mm, x̅ \u0026plusmn; SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of embryos transferred, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e262 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e558 (43.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDouble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e715 (56.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage of embryos transferred, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e857 (67.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 5/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e262 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e416 (32.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCOS: Controlled ovarian stimulation; aneuploidy; hCG: Human chorionic gonadotrophin; MII: Metaphase II.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCumulative Live Birth Rate was Higher in the PGT-A group\u003c/h3\u003e\n\u003cp\u003eThe PGT-A group underwent 230 COS cycles, while the non-PGT-A group underwent 1,192 COS cycles. Given the significant impact of maternal age on embryo euploidy (Cimadomo, Capalbo, Dovere, Tacconi, Soscia, Giancani, Scepi, Maggiulli, Vaiarelli, Rienzi and Ubaldi, 2021) and the need to adjust for covariates, patients were stratified into two age groups: \u0026le;35 years and \u0026gt;\u0026thinsp;35 years. Among women diagnosed with RPL, the application of PGT-A was significantly associated with an increased cumulative live birth rate (CLBR), at 58% vs. 38% (a\u003cem\u003eRR\u003c/em\u003e: 1.52, 95% CI [1.19\u0026ndash;1.93], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), regardless of age [Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e]. Stratified by age, CLBR was 70% vs. 51% (a\u003cem\u003eRR\u003c/em\u003e: 1.38, 95% CI [1.05\u0026ndash;1.82], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) for women\u0026thinsp;\u0026le;\u0026thinsp;35 years and 35% vs. 21% (a\u003cem\u003eRR\u003c/em\u003e: 1.69, 95% CI [1.03\u0026ndash;2.77], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037) for those\u0026thinsp;\u0026gt;\u0026thinsp;35 years. Furthermore, the multiple pregnancy rate was significantly lower in the PGT-A group, decreasing from 12\u0026ndash;3% (a\u003cem\u003eRR\u003c/em\u003e: 0.22, 95% CI [0.08\u0026ndash;0.62], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) among patients\u0026thinsp;\u0026le;\u0026thinsp;35 years. Among those\u0026thinsp;\u0026gt;\u0026thinsp;35 years, the multiple pregnancy rate was 0% vs. 4% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.155) [Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSecondary outcomes, including live birth rate (LBR), clinical pregnancy rate, early miscarriage rate, and late miscarriage rate per embryo transfer (ET), for the PGT-A and non-PGT-A groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The adjusted risk ratios (a\u003cem\u003eRR\u003c/em\u003e) comparing the PGT-A and non-PGT-A groups are shown, with subgroup analyses based on fresh embryo transfer or FET for pregnancy outcomes presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Notably, the results indicated that the application of PGT-A significantly increased the LBR, from 36\u0026ndash;51% (a\u003cem\u003eRR\u003c/em\u003e: 1.42, 95% CI [1.13\u0026ndash;1.80], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), regardless of age. In women\u0026thinsp;\u0026gt;\u0026thinsp;35 years, the LBR increased from 22\u0026ndash;41% (a\u003cem\u003eRR\u003c/em\u003e: 1.90, 95% CI [1.14\u0026ndash;3.15], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012). Furthermore, both the early and late miscarriage rates were significantly reduced with PGT-A. The early miscarriage rate decreased from 13\u0026ndash;7% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030), and the late miscarriage rate decreased from 3\u0026ndash;0% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016) in patients\u0026thinsp;\u0026le;\u0026thinsp;35 years.\u003c/p\u003e \u003cp\u003eWhen compared with the non-PGT-A FET subgroup, PGT-A significantly increased the LBR, from 31\u0026ndash;51% (a\u003cem\u003eRR\u003c/em\u003e: 1.65, 95% CI [1.28\u0026ndash;2.13], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), regardless of age. In women\u0026thinsp;\u0026gt;\u0026thinsp;35 years, the LBR increased from 17\u0026ndash;41% (a\u003cem\u003eRR\u003c/em\u003e: 2.38, 95% CI [1.39\u0026ndash;4.06], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Furthermore, in patients\u0026thinsp;\u0026le;\u0026thinsp;35 years, PGT-A reduced the miscarriage rate. The early miscarriage rate decreased from 15\u0026ndash;7% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014), and the late miscarriage rate decreased from 3\u0026ndash;0% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022). Additionally, when subgroup analysis was performed for non-PGT-A fresh embryo transfer, PGT-A reduced the late miscarriage rate, from 3\u0026ndash;0% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013) in patients\u0026thinsp;\u0026le;\u0026thinsp;35 years.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of cumulative live birth rate between PGT-A and non-PGT-A groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePGT‑A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon‑PGT-A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ea\u003cem\u003eRR\u003c/em\u003e (95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of COS cycles (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eCumulative live birth rate (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134/230 (58.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e458/1,192 (38.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.52 (1.19, 1.93)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108/155 (69.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e359/710 (50.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.38 (1.05, 1.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingleton\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104/155 (67.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e277/710 (39.01%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.72 (1.29, 2.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/155 (2.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82/710 (11.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.22 (0.08, 0.62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge \u0026gt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26/75 (34.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99/482 (20.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.69 (1.03, 2.77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingleton\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26/75 (34.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80/482 (16.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.09 (1.26, 3.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/75 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19/482 (3.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCOS: Controlled ovarian stimulation; a\u003cem\u003eRR\u003c/em\u003e: adjusted risk ratio.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical outcomes between PGT‑A and non-PGT-A groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePGT‑A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon‑PGT-A group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon‑PGT-A\u003c/p\u003e \u003cp\u003eFresh ET\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNon‑PGT-A\u003c/p\u003e \u003cp\u003eFrozen ET\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eNumber of ET cycles (n)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e507\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e766\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eClinical pregnancy rate (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155/262 (59.16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e677/1273 (53.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e303/507 (59.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e374/766 (48.83%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124/199 (62.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e507/818 (61.98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e247/392 (63.01%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e260/426 (61.03%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31/63 (49.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170/455 (37.36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56/115 (48.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e114/340 (33.53%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eLive birth rate (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134/262 (51.15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e458/1273 (35.98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e221/507 (43.59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e237/766 (30.94%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108/199 (54.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e359/818 (43.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e181/392 (46.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e178/426 (41.78%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26/63 (41.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99/455 (21.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40/115 (34.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59/340 (17.35%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eEarly miscarriage rate (\u0026le;\u0026thinsp;12w) (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/262 (6.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e163/1273 (12.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57/507 (11.24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e106/766 (13.84%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14/199 (7.04%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108/818 (13.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45/392 (11.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63/426 (14.79%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/63 (4.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55/455 (12.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12/115 (10.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43/340 (12.65%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eLate miscarriage rate (\u0026gt;12w) (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/262 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33/1273 (2.59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15/507 (2.96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18/766 (2.35%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/199 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25/818 (3.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13/392 (3.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12/426 (2.82%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/63 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/455 (1.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/115 (1.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6/340 (1.76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eET: Embryo transfer.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study results demonstrate a significant increase in cumulative live birth rate and a notable reduction in both early and late miscarriage rates with the use of PGT-A in women with recurrent pregnancy loss, consistent with previous reports (Bhatt, Marchetto, Roy, Morelli and McGovern, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2021\u003c/span\u003e, Mumusoglu, Telek and Ata, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Additionally, we observed an increased LBR when comparing non-PGT-A FET subgroup, but no significant difference was found when comparing non-PGT-A fresh embryo transfer. Our study is the first to analyze fresh embryo transfer and FET as subgroups. In general, fresh embryo transfer is performed in patients with favorable pregnancy prognoses, who typically exhibit a good ovarian response, an adequate number of retrieved oocytes, and multiple high-quality embryos available for transfer. These findings underscore the importance of the cumulative live birth rate as the primary endpoint in clinical trials.\u003c/p\u003e \u003cp\u003eAccording to the recommendations of the ASRM, there is insufficient evidence to support the routine use of PGT-A in all couples with infertility. Previous studies have reported that among women with a good prognosis for live birth, conventional IVF achieves a cumulative live birth rate that is noninferior to that of PGT-A, regardless of maternal age (\u0026le;\u0026thinsp;35 years or \u0026gt;\u0026thinsp;35 years) (Yan, et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In our study, we demonstrate that, for patients with RPL, who may have a less favorable prognosis, PGT-A significantly improves cumulative live birth rates, regardless of maternal age (\u0026le;\u0026thinsp;35 years or \u0026gt;\u0026thinsp;35 years). Additionally, although the number of embryos transferred per cycle was lower in the PGT-A group, this led to a significant reduction in the multiple pregnancy rate. The transfer of multiple embryos increases the incidence of multiple pregnancies, highlighting the associated risks. The PGT-A approach, which involves transferring a single euploid embryo, not only reduced miscarriage rate but also minimized the occurrence of multiple pregnancies.\u003c/p\u003e \u003cp\u003eThe theoretical benefit of PGT-A lies in its ability to screen embryos for chromosomal abnormalities prior to implantation. Several studies have investigated the relationship between euploidy rates and various factors, including patients\u0026rsquo; reproductive history, PGT-A diagnoses, and implantation outcomes following euploid blastocyst transfer. However, maternal age at the time of oocyte retrieval has consistently been identified as the only significant factor influencing mean euploidy rates per biopsied blastocyst. Previous findings have demonstrated no significant association between euploidy rates and factors such as prior live births, miscarriages, failed in IVF cycles, or implantation failures (Cimadomo, Capalbo, Dovere, Tacconi, Soscia, Giancani, Scepi, Maggiulli, Vaiarelli, Rienzi and Ubaldi, 2021). Recent evidence, however, suggests a significantly higher incidence of chromosomal abnormalities in blastocysts from younger patients (\u0026le;\u0026thinsp;35 years) with idiopathic recurrent pregnancy loss (iRPL) (48.9%) compared to those with no or sporadic clinical miscarriages (36.9%), while no significant difference has been observed in blastocysts from patients over 35 years (Liu, et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Chen et al. (Yan, Qin, Zhao, Sun, Gong, Li, Sun, Ling, Li, Hao, Tan, Yang, Zhu, Liu, Chen, Wei, Lu, Ni, Zhou, Wu, Gao, Shi, Lu, Zhang, Wu, Ma, Ma, Fu, Zhang, Meng, Zhang, Legro and Chen, 2021) reported that among women aged 20 to 37 years, the proportion of euploid embryos was 1,262 out of 1,809 (69.8%). In our center, the proportion of euploid embryos in women with RPL under 35 years of age was 58.4%. These findings indicate a significantly higher prevalence of chromosomal abnormalities in blastocysts from younger patients (\u0026le;\u0026thinsp;35 years) with RPL compared to those with no or sporadic clinical miscarriages. Accordingly, the greater improvement in pregnancy outcomes observed in patients under 35 years is likely attributable to the reduction in aneuploid miscarriages associated with the use of PGT-A. Our findings support the implantation checkpoint hypothesis (PCotASfR, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2012\u003c/span\u003e), which suggests that, for optimal reproductive success, the endometrium at the time of implantation must be both receptive and selective. An endometrium that is excessively receptive but insufficiently selective may lead to rapid conceptions but also to a high incidence of early pregnancy losses due to abnormalities in the implanting embryo.\u003c/p\u003e \u003cp\u003eThe primary objective of PGT-A is to facilitate the birth of a healthy child while reducing the burden of implantation failures and miscarriages (Sermon, et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Compared to the expected clinical miscarriage rate of 15\u0026ndash;25% (PCotASfR, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2012\u003c/span\u003e), our study demonstrated a significantly lower early miscarriage rate in the PGT-A group (6% overall, 7% for patients\u0026thinsp;\u0026le;\u0026thinsp;35 years, and 4% for those\u0026thinsp;\u0026gt;\u0026thinsp;35 years). Consistent with previous studies, our findings confirm a reduced incidence of early pregnancy loss in the PGT-A group, regardless of maternal age (Rubio, et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2017\u003c/span\u003e, Verpoest, et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Yan, et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). These results suggest that PGT-A improves embryo selection, thereby increasing the likelihood of embryos progressing beyond the first trimester.\u003c/p\u003e \u003cp\u003eIt is important to note that our trial has several limitations. One limitation is its retrospective design, which inherently relies on pre-existing data and may introduce selection bias. Additionally, the study population is restricted to women with RPL undergoing IVF, potentially for indications beyond RPL, and does not encompass all RPL patients who may not require IVF. The PGT-A plus FET strategy employed in the PGT-A group presents a potential source of bias in the analysis of pregnancy outcomes, as the non-PGT-A group included both fresh and frozen-thawed transfers at the cleavage and blastocyst stages. Prior evidence suggests that blastocyst transfer yields higher implantation and live birth rates, which likely influenced the observed outcomes between the two groups (Glujovsky, et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Moreover, it is essential to highlight that, compared to fresh embryo transfers without PGT-A, the application of PGT-A does not confer any improvement in pregnancy outcomes. Furthermore, the genetic testing platform used for PGT-A, whether aCGH or NGS, was not specified in the dataset. This omission prevents any assessment of potential variations in outcomes based on the testing methodology.\u003c/p\u003e \u003cp\u003eAdditionally, it remains uncertain whether PGT-A improves pregnancy and live birth rates in these patients beyond its baseline utility. Furthermore, for patients with RPL without infertility\u0026mdash;who would not otherwise pursue IVF\u0026mdash;it is uncertain whether IVF for PGT-A is a worthwhile investment of time and resources. Moreover, the PGT-A strategy typically involves the use of FET, which studies suggest may increase the risk of maternal hypertensive disorders, as well as the likelihood of delivering a large-for-gestational-age baby and higher birth weight (Zaat, et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Ideally, one or more fetal aneuploidies diagnosed in previous POC should warrant further evaluation. However, the current rate of aneuploidy diagnosis in POC remains relatively low.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, despite these limitations, our study provides compelling evidence supporting the use of PGT-A in women experiencing RPL. The findings demonstrate that the selection of euploid embryos through PGT-A for FET significantly improves the cumulative live birth rate compared to the use of untested embryos. This evidence can assist clinicians in guiding personalized treatment strategies for this challenging condition. However, the effectiveness of PGT-A for the treatment of RPL, particularly in individuals undergoing fresh embryo transfer, remains inconclusive.Furthermore, large, well-designed randomized controlled trials (RCTs) are needed to further clarify the benefits of PGT-A in improving cumulative live birth rate and reducing miscarriage risk among couples with unexplained RPL.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This study was approved by the Ethics Committee of Nanjing Drum Tower Hospital (Approval No.: 2021-384-01). Written informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;None.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This work was supported by the National Natural Science Foundation of China (Grant No. 82301891 to Y.L.P) and the National Natural Science Foundation of China (Grant No. 82371678 to M.J).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Y.L.P participated in study design, analysis, manuscript drafting, and critical discussion.\u003cbr\u003e\u0026nbsp;K.N, L.J.Y, H.F.F, and Z.N.Y participated in study analysis, execution, statistical analysis, and critical discussion.\u003cbr\u003e\u0026nbsp;M.J participated in study design, execution, statistical analysis, manuscript drafting, and critical discussion.\u003cbr\u003e\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;We appreciate all the members of the Reproductive Medicine Center, Nanjing Drum Tower Hospital for providing the clinical information database.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Mcheik S, Peramo B, Quenby S. ESHRE guideline: recurrent pregnancy loss: an update in 2022. \u003cem\u003eHuman reproduction open\u003c/em\u003e 2023;2023: hoad002.\u003c/li\u003e\n\u003cli\u003eBhatt SJ, Marchetto NM, Roy J, Morelli SS, McGovern PG. Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study. \u003cem\u003eHuman reproduction (Oxford, England)\u003c/em\u003e 2021;36: 2339-2344.\u003c/li\u003e\n\u003cli\u003eBramham K, Hunt B, Germain S, Calatayud I, Khamashta M, Bewley S, Nelson-Piercy C. Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. \u003cem\u003eLupus\u003c/em\u003e 2010;19: 58-64.\u003c/li\u003e\n\u003cli\u003eCimadomo D, Capalbo A, Dovere L, Tacconi L, Soscia D, Giancani A, Scepi E, Maggiulli R, Vaiarelli A, Rienzi L\u003cem\u003e et al.\u003c/em\u003e Leave the past behind: women\u0026apos;s reproductive history shows no association with blastocysts\u0026apos; euploidy and limited association with live birth rates after euploid embryo transfers. \u003cem\u003eHuman reproduction (Oxford, England)\u003c/em\u003e 2021;36: 929-940.\u003c/li\u003e\n\u003cli\u003eDaar J, Benward J, Collins L, Davis J, Francis L, Gates E, Ginsburg E, Klipstein S, Koenig B, La Barbera A. Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion. \u003cem\u003eFertility and sterility\u003c/em\u003e 2017;107: 1130-1135.\u003c/li\u003e\n\u003cli\u003eDong AC, Morgan J, Kane M, Stagnaro-Green A, Stephenson MD. Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis. \u003cem\u003eFertility and sterility\u003c/em\u003e 2020;113: 587-600. e581.\u003c/li\u003e\n\u003cli\u003eFranssen MT, Korevaar JC, Leschot NJ, Bossuyt PM, Knegt AC, Gerssen-Schoorl KB, Wouters CH, Hansson KB, Hochstenbach R, Madan K. Selective chromosome analysis in couples with two or more miscarriages: case-control study. \u003cem\u003ebmj\u003c/em\u003e 2005;331: 137-141.\u003c/li\u003e\n\u003cli\u003eGardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. \u003cem\u003eFertility and sterility\u003c/em\u003e 2000;73: 1155-1158.\u003c/li\u003e\n\u003cli\u003eGlujovsky D, Retamar AMQ, Sedo CRA, Ciapponi A, Cornelisse S, Blake D. Cleavage‐stage versus blastocyst‐stage embryo transfer in assisted reproductive technology. \u003cem\u003eCochrane database of systematic reviews\u003c/em\u003e 2022.\u003c/li\u003e\n\u003cli\u003eGreco E, Litwicka K, Minasi MG, Cursio E, Greco PF, Barillari P. Preimplantation genetic testing: where we are today. \u003cem\u003eInternational journal of molecular sciences\u003c/em\u003e 2020;21: 4381.\u003c/li\u003e\n\u003cli\u003eKutteh WH, Papas RS, Maisenbacher MK, Dahdouh EM. Role of genetic analysis of products of conception and PGT in managing early pregnancy loss. \u003cem\u003eReproductive BioMedicine Online\u003c/em\u003e 2024;49: 103738.\u003c/li\u003e\n\u003cli\u003eLiu X-Y, Fan Q, Wang J, Li R, Xu Y, Guo J, Wang Y-Z, Zeng Y-H, Ding C-H, Cai B. Higher chromosomal abnormality rate in blastocysts from young patients with idiopathic recurrent pregnancy loss. \u003cem\u003eFertility and sterility\u003c/em\u003e 2020;113: 853-864.\u003c/li\u003e\n\u003cli\u003eMastenbroek S, Twisk M, Van Der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. \u003cem\u003eHuman reproduction update\u003c/em\u003e 2011;17: 454-466.\u003c/li\u003e\n\u003cli\u003eMumusoglu S, Telek SB, Ata B. Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis. \u003cem\u003eFertility and sterility\u003c/em\u003e 2025;123: 121-136.\u003c/li\u003e\n\u003cli\u003eMunn\u0026eacute; S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. \u003cem\u003eFertility and sterility\u003c/em\u003e 2019;112: 1071-1079. e1077.\u003c/li\u003e\n\u003cli\u003eOzgur K, Berkkanoglu M, Bulut H, Yoruk GDA, Candurmaz NN, Coetzee K. Single best euploid versus single best unknown-ploidy blastocyst frozen embryo transfers: a randomized controlled trial. \u003cem\u003eJournal of Assisted Reproduction and Genetics\u003c/em\u003e 2019;36: 629-636.\u003c/li\u003e\n\u003cli\u003ePCotASfR M. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. \u003cem\u003eFertility and sterility\u003c/em\u003e 2012;98: 1103-1111.\u003c/li\u003e\n\u003cli\u003ePCotASfR M. Definitions of infertility and recurrent pregnancy loss: a committee opinion. \u003cem\u003eFertility and sterility\u003c/em\u003e 2020;113: 533-535.\u003c/li\u003e\n\u003cli\u003ePopescu F, Jaslow C, Kutteh W. Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients. \u003cem\u003eHuman Reproduction\u003c/em\u003e 2018;33: 579-587.\u003c/li\u003e\n\u003cli\u003eRubio C, Bellver J, Rodrigo L, Castill\u0026oacute;n G, Guill\u0026eacute;n A, Vidal C, Giles J, Ferrando M, Cabanillas S, Remoh\u0026iacute; J. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. \u003cem\u003eFertility and sterility\u003c/em\u003e 2017;107: 1122-1129.\u003c/li\u003e\n\u003cli\u003eSacchi L, Albani E, Cesana A, Smeraldi A, Parini V, Fabiani M, Poli M, Capalbo A, Levi-Setti PE. Preimplantation genetic testing for aneuploidy improves clinical, gestational, and neonatal outcomes in advanced maternal age patients without compromising cumulative live-birth rate. \u003cem\u003eJournal of assisted reproduction and genetics\u003c/em\u003e 2019;36: 2493-2504.\u003c/li\u003e\n\u003cli\u003eSawada Y, Sato T, Saito C, Ozawa F, Ozaki Y, Sugiura-Ogasawara M. Clinical utility of decorin in follicular fluid as a biomarker of oocyte potential. \u003cem\u003eReproductive Biology\u003c/em\u003e 2018;18: 33-39.\u003c/li\u003e\n\u003cli\u003eSermon K, Capalbo A, Cohen J, Coonen E, De Rycke M, De Vos A, Delhanty J, Fiorentino F, Gleicher N, Griesinger G. The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. \u003cem\u003eMHR: Basic science of reproductive medicine\u003c/em\u003e 2016;22: 845-857.\u003c/li\u003e\n\u003cli\u003eSugiura-Ogasawara M, Ozaki Y, Kitaori T, Kumagai K, Suzuki S. Midline uterine defect size is correlated with miscarriage of euploid embryos in recurrent cases. \u003cem\u003eFertility and sterility\u003c/em\u003e 2010;93: 1983-1988.\u003c/li\u003e\n\u003cli\u003eSui Y-L, Lei C-X, Ye J-F, Fu J, Zhang S, Li L, Peng X-D, Zhang Y-P, Chen G-W, Sun X-X. In vitro fertilization with single-nucleotide polymorphism microarray-based preimplantation genetic testing for aneuploidy significantly improves clinical outcomes in infertile women with recurrent pregnancy loss: a randomized controlled trial. \u003cem\u003eReproductive and Developmental Medicine\u003c/em\u003e 2020;4: 32-41.\u003c/li\u003e\n\u003cli\u003eVerpoest W, Staessen C, Bossuyt PM, Goossens V, Altarescu G, Bonduelle M, Devesa M, Eldar-Geva T, Gianaroli L, Griesinger G. Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial. \u003cem\u003eHuman reproduction\u003c/em\u003e 2018;33: 1767-1776.\u003c/li\u003e\n\u003cli\u003eWilkinson J, Roberts SA, Vail A. Developments in IVF warrant the adoption of new performance indicators for ART clinics, but do not justify the abandonment of patient-centred measures. \u003cem\u003eHuman Reproduction\u003c/em\u003e 2017;32: 1155-1159.\u003c/li\u003e\n\u003cli\u003eYan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, Sun X, Ling X, Li H, Hao C\u003cem\u003e et al.\u003c/em\u003e Live Birth with or without Preimplantation Genetic Testing for Aneuploidy. \u003cem\u003eN Engl J Med\u003c/em\u003e 2021;385: 2047-2058.\u003c/li\u003e\n\u003cli\u003eZaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. \u003cem\u003eCochrane Database of Systematic Reviews\u003c/em\u003e 2021.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[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":"Recurrent pregnancy loss, preimplantation genetic testing for aneuploidy, cumulative live birth rate, miscarriage","lastPublishedDoi":"10.21203/rs.3.rs-6399928/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6399928/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate whether preimplantation genetic testing for aneuploidy to deselect aneuploid embryos improves cumulative live birth rate and reduces miscarriage risk in normal karyotype couples with recurrent pregnancy loss undergoing assisted reproductive technology.\u003c/p\u003e\u003ch2\u003eDesign:\u003c/h2\u003e \u003cp\u003eRetrospective cohort study.\u003c/p\u003e\u003ch2\u003eSubjects:\u003c/h2\u003e \u003cp\u003eA total of 1,039 couples with recurrent pregnancy loss who underwent assisted reproductive treatment between January 2013 and December 2023.\u003c/p\u003e\u003ch2\u003eExposure:\u003c/h2\u003e \u003cp\u003ePatients were stratified into two groups based on their decision to undergo preimplantation genetic testing for aneuploidy.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong women with recurrent pregnancy loss, preimplantation genetic testing for aneuploidy increased the cumulative live birth rate to 70% compared to 51% in women\u0026thinsp;\u0026le;\u0026thinsp;35 years (adjusted risk ratio, 1.38; 95% confidence interval, 1.05\u0026ndash;1.82; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) and to 35% compared to 21% in women\u0026thinsp;\u0026gt;\u0026thinsp;35 years (adjusted risk ratio, 1.69; 95% confidence interval, 1.03\u0026ndash;2.77; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037). Preimplantation genetic testing reduced the early miscarriage rate to 7% vs. 13%, (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030) and the late miscarriage rate to 0% vs. 3% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016) in women\u0026thinsp;\u0026le;\u0026thinsp;35 years. Subgroup analysis revealed that the significant benefit of preimplantation genetic testing diminished in patients undergoing fresh embryo transfers.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePreimplantation genetic testing for aneuploidy significantly increased the cumulative live birth rate in couples with recurrent pregnancy loss across both age groups (\u0026le;\u0026thinsp;35 years and \u0026gt;\u0026thinsp;35 years) and reduced early and late miscarriage rates in those\u0026thinsp;\u0026le;\u0026thinsp;35 years. However, its benefits diminished in patients undergoing fresh embryo transfers, suggesting that the embryo transfer strategy may influence its effectiveness.\u003c/p\u003e","manuscriptTitle":"Preimplantation Genetic Testing for Aneuploidy Improves Cumulative Live Birth Rate and Reduces Miscarriage in Recurrent Pregnancy Loss","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-08 20:37:29","doi":"10.21203/rs.3.rs-6399928/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":"71738cb5-e568-48f4-8f8d-bee90cb2850b","owner":[],"postedDate":"May 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T10:38:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-08 20:37:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6399928","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6399928","identity":"rs-6399928","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}