Comparative analysis of cumulative live birth rates in patients with recurrent pregnancy loss undergoing preimplantation genetic testing for aneuploidy versus conventional in vitro fertilisation/intracytoplasmic sperm injection: a retrospective study.

From June 2016 to June 2022, 24,817 patients underwent PGT-A or IVF/ICSI treatment at our centre. Following the inclusion and exclusion criteria, 198 RPL patients who received PGT-A treatment and 156 RPL patients who underwent IVF/ICSI treatment were included in the final analysis. Significant differences were observed between the PGT-A and IVF-ICSI groups in terms of maternal BMI, number of miscarriages, oocyte yield, endometrial thickness on the day of transfer, and infertility diagnosis type (female factors and other factors) ( P  < 0.05, Table  1 ). However, no significant between-group differences were observed in maternal age, paternal age, paternal BMI, maternal delivery history, duration of infertility, baseline antral follicle count, or the number of high-quality embryos transferred ( P  > 0.05, Table  1 ). Subgroup analysis revealed additional stratified differences based on maternal age and the number of miscarriages. For patients aged ≥ 35 years, significant differences were found in the number of previous miscarriages, oocyte yield, endometrial thickness, and infertility diagnosis between the PGT-A and IVF/ICSI groups ( P  < 0.05, Supplementary Table 1 ). Among patients aged < 35 years, only infertility diagnosis showed a significant difference between the two groups ( P  < 0.05, Supplementary Table 1 ). For patients with two previous miscarriages, significant differences were observed in endometrial thickness on the day of transfer and infertility diagnosis between the two groups. In contrast, for patients with at least three previous miscarriages, significant between-group differences were noted in maternal BMI and infertility diagnosis ( P  < 0.05, Supplementary Table 2 ). All other baseline characteristics remained comparable between the two groups across all subgroup analyses for other variables. Table 1 Comparison of baseline characteristics between the PGT-A and IVF/ICSI groups Item PGT-A group IVF/ICSI group t/Z/χ 2 value P value a No. of cases 198 156 Maternal age (years) 33.04 ± 4.09 33.62 ± 4.198 -1.27 0.205 Paternal age (years) 33.67 ± 4.80 34.20 ± 5.57 -0.95 0.344 Maternal BMI (kg/m 2 ) 23.75 ± 2.81 24.40 ± 3.12 -2.06 0.040* Paternal BMI (kg/m 2 ) 25.95 ± 3.63 25.61 ± 3.44 0.61 0.809 Maternal parity (nulliparous) 79.80 (158/198) 78.21 (122/156) 0.13 0.714 Duration of infertility (years) 2.00 ± 1.52 2.27 ± 1.86 -1.13 0.261 No. of previous abortions 2.64 ± 1.04 2.28 ± 0.94 3.42 0.001* Antral follicle count in both ovaries 16.93 ± 6.73 18.45 ± 7.82 -1.93 0.055 No. of retrieved oocytes 13.84 ± 7.86 15.67 ± 7.21 -2.26 0.025* Good-quality embryos transferred 0.62 ± 0.49 0.67 ± 0.47 -1.03 0.304 Endometrial thickness at the day of embryo transfer (mm) 8.60 ± 1.46 9.15 ± 1.99 -3.26 0.001* Infertility diagnosis b  Female factor 48.48 (96/198) 65.38 (102/156) 10.11 0.001*  Male factor 7.57 (15/198) 8.33 (13/156) 0.07 0.793  Combined factors 8.08 (16/198) 13.46 (21/156) 2.70 0.100  Others 35.86 (71/198) 12.82 (20/156) 24.25 0.000* Note: Data are presented as the mean ± standard deviation or n (%). ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; PGT-A, preimplantation genetic testing for aneuploidy; N/A, not applicable; BMI, body mass index a ‘*’ P  < 0.05 indicates statistical significance b The causes of infertility and indications for PGT-A are not mutually exclusive Comparison of baseline characteristics between the PGT-A and IVF/ICSI groups Note: Data are presented as the mean ± standard deviation or n (%). ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; PGT-A, preimplantation genetic testing for aneuploidy; N/A, not applicable; BMI, body mass index a ‘*’ P  < 0.05 indicates statistical significance b The causes of infertility and indications for PGT-A are not mutually exclusive A total of 198 patients in the PGT-A group and 156 patients in the IVF/ICSI group completed their first transfer cycle, with 45 and 29 patients proceeding to a second transfer cycle and 12 and seven patients proceeding to a third transfer cycle in the respective groups. Although the time to live birth was significantly longer in the PGT-A group than in the IVF/ICSI group, no significant between-group differences were observed in the pregnancy rate per transfer (aOR = 0.76; 95% CI: 0.50–1.16; P  > 0.05, Table  2 ), miscarriage rate per pregnancy (aOR = 0.81; 95% CI: 0.42–1.55; P  > 0.05, Table  2 ), or live birth rate per pregnancy (aOR = 0.90; 95% CI: 0.60–1.35; P  > 0.05, Table  2 ). The prolonged time to live birth in the PGT-A group (adjusted HR [aHR] = 0.56; 95% CI: 0.42–0.75; P  < 0.05, Table  2 ) may be attributable to the additional procedural steps required for PGT-A treatment, such as embryo biopsy, vitrification, and genetic analysis, which tend to extend the treatment cycle duration. This delay could impose a considerable burden on patients with AMA or diminished ovarian reserve. Among patients aged ≥ 35 years, no significant differences were observed in the pregnancy rate, miscarriage rate, or live birth rate between the PGT-A and IVF/ICSI groups ( P  > 0.05, Supplementary Table 3 ). Similarly, for patients aged  0.05, Supplementary Table 3 ). However, the time to live birth in those aged < 35 years was significantly longer in the PGT-A group than in the IVF-ICSI group (aHR = 0.46; 95% CI: 0.33–0.65; P  < 0.05, Supplementary Table 3 ). These findings suggest that although PGT-A is designed to improve live birth rates by avoiding the transfer of aneuploid embryos, it does not reduce the time to live birth in women aged under 35 years or improve the CLBR in any age group. For patients with at least three previous miscarriages, the outcomes were comparable between the two groups ( P  > 0.05, Supplementary Table 4 ). Similarly, among patients with two previous miscarriages, no significant between-group differences were observed in the live birth rate, pregnancy rate, or miscarriage rate. However, for patients with two prior miscarriages, the time to live birth was significantly longer in the PGT-A group than in the IVF/ICSI group (aHR = 0.59; 95% CI: 0.43–0.83, Supplementary Table 4 ). This raises concerns about the cost-effectiveness of PGT-A and its applicability for patients requiring timely outcomes. These limitations should be carefully considered when counselling patients, particularly those with AMA or prior miscarriages. Table 2 Comparison of embryo outcomes between the PGT-A and IVF/ICSI groups Item PGT-A group IVF/ICSI group t/χ 2 value P value a aOR b /aHR c 95% CI P value a No. of cycles 255 192 Clinical pregnancy rate 58.82 (150/255) 67.71 (130/192) 3.70 0.055 0.760 (0.50–1.16) 0.202 Miscarriage rate 19.46 (29/149) 21.09 (27/128) 0.11 0.736 0.807 (0.42–1.55) 0.520 Live birth rate 47.06 (120/255) 52.60 (101/192) 1.35 0.246 0.902 (0.60–1.35) 0.617 Time to live birth 408.76 ± 141.77 333.70 ± 84.82 4.86 0.000 0.557 (0.42–0.75) 0.000* Note: IVF: in vitro fertilisation; ICSI: Intracytoplasmic sperm injection; PGT-A: Preimplantation genetic testing for aneuploidy; CI: confidence interval a ‘*’ P  < 0.05 indicates statistical significance b Odds ratio (95% CI) adjusted for maternal body mass index, number of previous abortions, number of retrieved oocytes, endometrial thickness on the day of embryo transfer, and infertility diagnosis (including female factors and other factors) c Hazard ratio (95% CI) adjusted for maternal body mass index, number of previous abortions, number of retrieved oocytes, endometrial thickness at the day of embryo transfer, and infertility diagnosis (including female factors and other factors) using Cox regression analysis Comparison of embryo outcomes between the PGT-A and IVF/ICSI groups Note: IVF: in vitro fertilisation; ICSI: Intracytoplasmic sperm injection; PGT-A: Preimplantation genetic testing for aneuploidy; CI: confidence interval a ‘*’ P  < 0.05 indicates statistical significance b Odds ratio (95% CI) adjusted for maternal body mass index, number of previous abortions, number of retrieved oocytes, endometrial thickness on the day of embryo transfer, and infertility diagnosis (including female factors and other factors) c Hazard ratio (95% CI) adjusted for maternal body mass index, number of previous abortions, number of retrieved oocytes, endometrial thickness at the day of embryo transfer, and infertility diagnosis (including female factors and other factors) using Cox regression analysis In the first three transfer cycles, no significant differences were observed in the conservative CLBR between the PGT-A and IVF/ICSI groups (Cycle 1: aOR = 0.78, 95% CI: 0.49–1.23; Cycle 2: aOR = 0.81, 95% CI: 0.51–1.29; Cycle 3: aOR = 0.96, 95% CI: 0.60–1.53; P  > 0.05, Table  3 ). Similarly, the optimal CLBR after three transfer cycles showed no significant differences between the two groups ( P  > 0.05, Table  4 ). These findings suggest that, despite the theoretical advantage of PGT-A in screening euploid embryos, its effectiveness in improving the CLBR is not significant under real-world clinical conditions. Factors such as embryo mosaicism, potential loss of transferable embryos during biopsy, and variability in laboratory practices may undermine the effectiveness of PGT-A. Subgroup analysis by maternal age revealed no significant differences in the conservative or optimal CLBR between the PGT-A and IVF/ICSI groups in patients aged ≥ 35 years or  0.05, Supplementary Tables 5 and 6 ). Similarly, among patients with two miscarriages or at least three miscarriages, no significant differences were observed in the conservative or optimal CLBR between the two groups ( P  > 0.05, Supplementary Tables 7 and 8 ). Overall, these findings indicate that although PGT-A offers a theoretical advantage in decreasing the risk of transferring aneuploid embryos, its potential benefits may be offset by practical challenges, such as the complexity of the procedure and potential adverse effects on embryo viability. Table 3 Comparison of Conservative cumulative live birth rates between the PGT-A and IVF/ICSI groups Item PGT-A group IVF/ICSI group χ 2 value P value a aOR b 95% CI P value a No. of cases 198 156 Total number of live births after the first transfer 48.48 (96/198) 58.97 (92/156) 3.86 0.050 0.78 (0.49–1.23) 0.282 Total number of live births after the second transfer 57.58 (114/198) 64.74 (101/156) 1.88 0.170 0.81 (0.51–1.29) 0.367 Total number of live births after the third transfer 60.61 (120/198) 64.74 (101/156) 0.64 0.425 0.96 (0.60–1.53) 0.848 Note: Data are presented as the mean ± standard deviation or n (%). ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; N/A, not applicable; PGT-A, preimplantation genetic testing for aneuploidy; CI, confidence interval a ‘*’ P  < 0.05 was statistically significant b Odds ratio (95% CI) adjusted for maternal body mass index, number of previous abortions, number of retrieved oocytes, endometrial thickness at the day of embryo transfer, and infertility diagnosis (including female factors and other factors) Comparison of Conservative cumulative live birth rates between the PGT-A and IVF/ICSI groups Note: Data are presented as the mean ± standard deviation or n (%). ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; N/A, not applicable; PGT-A, preimplantation genetic testing for aneuploidy; CI, confidence interval a ‘*’ P  < 0.05 was statistically significant b Odds ratio (95% CI) adjusted for maternal body mass index, number of previous abortions, number of retrieved oocytes, endometrial thickness at the day of embryo transfer, and infertility diagnosis (including female factors and other factors) Table 4 Comparison of optimal cumulative live birth rates between the PGT-A and IVF/ICSI groups Item PGT-A group IVF/ICSI group χ 2 value P value No. of cases 198 156 Proportion of live births after the first transplant 48.48 58.97 Proportion of live births after the second transplant 69.09 71.71 Proportion of live births after the third transplant 84.55 71.71 1.07 0.302 Note: ‘*’ P  < 0.05 indicates statistical significance. IVF, in vitro fertilisation; ICSI, intracytoplasmic sperm injection; PGT-A, preimplantation genetic testing for aneuploidy. Optimal CLBRs were calculated using the log-rank test Comparison of optimal cumulative live birth rates between the PGT-A and IVF/ICSI groups Note: ‘*’ P  < 0.05 indicates statistical significance. IVF, in vitro fertilisation; ICSI, intracytoplasmic sperm injection; PGT-A, preimplantation genetic testing for aneuploidy. Optimal CLBRs were calculated using the log-rank test The lack of significant differences in perinatal outcomes between the PGT-A and IVF/ICSI groups, as presented in Table  5 , may be attributable to several factors. Both groups involved RPL patients undergoing well-controlled assisted reproductive techniques, so the maternal and embryonic health conditions may have become standardised across treatments. Additionally, the selection of embryos for transfer– whether through PGT-A or morphological assessment in IVF/ICSI– may have ensured a baseline quality that minimised disparities in perinatal outcomes. Furthermore, the small sample size and homogeneity in clinical management protocols may have limited the power to detect subtle differences between the two groups. Table 5 Perinatal outcomes of live births resulting from PGT-A and IVF/ICSI Singleton pregnancies Item PGT-A group IVF/ICSI group t/χ 2 value P value a No. of live birth cases 120 101 Obstetric outcomes  Gestational hypertension 5.83 (7/120) 7.92 (8/101) 0.38 0.539  Pre-eclampsia 0 (0/120) 1.67 (2/101) 1.70 0.192  Gestational diabetes 8.33 (10/120) 2.97 (3/101) 2.85 0.091  Hypothyroidism during pregnancy 1.67 (2/120) 0 (0/101) 1.70 0.192  PROM 5.00 (6/120) 6.93 (7/101) 0.37 0.543  Placenta previa 1.67 (2/120) 0.99 (1/101) 0.19 0.665 Caesarean delivery 82.50 (99/120) 82.18 (83/101) 0.01 0.950 Neonatal outcomes  Gestational age (weeks) 38.03 ± 2.26 37.98 ± 2.06 0.15 0.879  Preterm delivery, < 37 weeks 12.50 (15/120) 11.88 (12/101) 0.02 0.889  Very preterm delivery, ≥28 weeks and < 32 weeks 3.33 (4/120) 2.97 (3/101) 0.02 0.878  Birth weight (g) 3342.79 ± 596.78 3345.79 ± 605.28 -0.04 0.971  Low birth weight, < 2,500 g 7.50 (9/120) 8.91 (3/101) 0.15 0.702  Very low birth weight, < 1,500 g 2.50 (3/120) 0.99 (1/101) 0.70 0.402 Birth height, cm 50.09 ± 2.69 50.03 ± 2.26 0.18 0.855 Birth defects 4.17 (5/120) 0 (0/101) 2.63 0.105 1-minute Apgar Scores 9.88 ± 0.48 9.95 ± 0.22 -1.55 0.144 Note: Data are presented as mean (SD) or n (%). ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; PGT-A, preimplantation genetic testing for aneuploidy; PROM, preterm premature rupture of membranes; N/A, not applicable a P  < 0.05 indicates statistical significance Perinatal outcomes of live births resulting from PGT-A and IVF/ICSI Singleton pregnancies Note: Data are presented as mean (SD) or n (%). ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; PGT-A, preimplantation genetic testing for aneuploidy; PROM, preterm premature rupture of membranes; N/A, not applicable a P  < 0.05 indicates statistical significance

This retrospective cohort study included RPL patients who underwent their initial oocyte retrieval cycle followed by at least one single fresh or frozen-thawed blastocyst transfer cycle as part of IVF/ICSI or PGT-A between June 2016 and June 2022 at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University. RPL patients voluntarily chose PGT-A or IVF/ICSI after comprehensive counselling by our specialised genetic counsellors, who provided detailed explanations of the advantages, limitations, and potential outcomes of both approaches. In the PGT-A group, only euploid embryos were selected for transfer, ensuring the exclusion of both aneuploid and mosaic embryos. Patients were required to meet strict inclusion and exclusion criteria. The inclusion criteria were as follows: (1) patients diagnosed with RPL, defined as having two or more clinical pregnancy losses documented by ultrasound or histopathology; (2) first oocyte retrieval cycle during the study period; and (3) at least one single-blastocyst transfer cycle following IVF/ICSI or PGT-A, with a single blastocyst transferred in each cycle. The exclusion criteria included known uterine anomalies, untreated uterine septa, adenomyosis or submucosal fibroids, endometrial polyps or intrauterine adhesions, contraindications to pregnancy, use of donor sperm, presence of autoimmune diseases, and second live births in the same patient. Patients who underwent cleavage-stage embryo transfers, double-blastocyst transfers, or combined IVF/ICSI and PGT-A cycles were also excluded, significantly narrowing the pool of eligible participants. Patients with incomplete clinical or follow-up data were also excluded to minimise potential bias (Fig.  1 ). Missing data were handled using multiple imputation techniques to ensure the robustness of the analyses. The final cohort comprised 196 PGT-A patients and 158 IVF/ICSI patients. Although the small sample size limits the statistical power of the subgroup analyses, it reflects a focus on rigorous inclusion and exclusion criteria to minimise confounding factors. The subgroup analyses were conducted based on maternal age and miscarriage frequency. These factors were chosen as they represent key clinical variables influencing RPL outcomes and potential modifiers of treatment efficacy. For example, AMA is associated with higher rates of aneuploidy, while the number of previous miscarriages may indicate the severity of RPL. This study complied with the ethical guidelines of China’s ‘Ethical Review Measures for Life Sciences and Medical Research Involving Humans’. Ethical approval was obtained from the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (approval number: 2024-052-01; Human Ethics and Consent to Participate declarations: not applicable; Clinical trial number: not applicable). Fig. 1 Study enrolment and exclusion flowchart Study enrolment and exclusion flowchart Ovarian stimulation, transvaginal ultrasound-guided oocyte retrieval, IVF/ICSI, embryo culture, blastocyst morphological assessment, embryo vitrification or thawing, embryo transfer, luteal phase support, trophectoderm biopsy, and three frozen embryo transfer protocols were performed as previously described by our centre’s researchers [ 19 – 22 ]. A good-quality blastocyst was defined as one with a score of 4BB or higher based on Gardner and Schoolcraft’s classification [ 23 ]. Biochemical pregnancy was diagnosed based on a positive human chorionic gonadotropin test at 14 days post-embryo transfer but the absence of a gestational sac on ultrasound at 6–7 weeks post-transfer. Clinical pregnancy was confirmed by the presence of an intrauterine gestational sac on ultrasound at 6–7 weeks of gestation. Miscarriage or termination of pregnancy was defined as pregnancy loss before 28 weeks of gestation. Live birth was defined as the delivery of a foetus with signs of life at ≥ 28 weeks of gestation, with multiple births counted as one live birth. Data on PGT-A and IVF/ICSI treatment cycles were retrieved from our hospital’s electronic medical record system. Data on pregnancy and perinatal outcomes for clinical pregnancies delivered at our hospital were also collected from the electronic medical record system. For patients who received treatment at our centre but delivered elsewhere, trained nurses contacted them to confirm pregnancy outcomes within 2 months of the expected delivery date. Data on RPL patients and their singleton live births achieved via PGT-A and IVF/ICSI at our centre were collected. Pregnancy-induced hypertension was defined as systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg recorded on two separate occasions at least 4 h apart after 20 weeks of gestation in previously normotensive women [ 24 ]. Pre-eclampsia was defined as the occurrence of proteinuria with systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg after 20 weeks of gestation in previously normotensive women [ 24 ]. Gestational diabetes was defined according to ACOG Practice Bulletin number 190 [ 25 ]. Hypothyroidism during pregnancy was defined according to the criteria established by Gietka-Czernel and Glinicki [ 26 ]. Conditions such as premature rupture of membranes; placenta previa; caesarean section; gestational age (weeks); preterm birth (defined as delivery before 37 weeks of gestation) and very preterm birth (defined as delivery between 28 and 31 weeks of gestation); birth weight (grams), including low birth weight (< 2,500 g) and very low birth weight (< 1,500 g); birth height (cm); congenital defects (as defined by Ran et al. [ 22 ]); and Apgar scores at 1 and 5 min were also collected. A priori sample size calculation determined that a minimum of 174 participants per group was required to detect a 10% absolute difference in the CLBR (e.g., 60% vs. 50%) with 80% power at a significance level of 0.05. This calculation assumed a 1:1 allocation ratio and accounted for an anticipated 10% loss to follow-up, leading to a target sample size of 192 participants per group. Although the final cohort included 196 PGT-A patients and 158 IVF/ICSI patients– slightly below the target for the IVF/ICSI group– post-hoc sensitivity analyses were conducted to address this limitation. Sensitivity analyses were performed to evaluate the robustness of the results under various assumptions about missing data and sample size. These included complete-case analyses and multiple imputation models to address potential biases introduced by excluded data. Additionally, subgroup-specific sensitivity analyses stratified by maternal age and miscarriage frequency were conducted to assess outcomes, given their roles as key clinical modifiers. For example, AMA is strongly associated with increased rates of aneuploidy, while the number of previous miscarriages reflects the severity and potential aetiology of RPL. Across all scenarios, the sensitivity analyses yielded consistent findings, supporting the reliability of the primary conclusions despite the slightly smaller-than-expected sample size in the IVF/ICSI group. All statistical analyses yielded consistent results, underscoring the reliability of the primary conclusions. The statistical analyses were conducted using SPSS 25.0 (IBM, Chicago, IL). Categorical variables are presented as frequencies and percentages and compared using the chi-square test or Fisher’s exact test. Continuous variables are presented as means ± standard deviations and compared using Student’s t-tests. Conservative and optimal CLBRs were calculated. The conservative CLBRs assumed that women who did not continue treatment never achieved live birth, whereas the optimal CLBRs assumed that patients who discontinued treatment had the same live birth probability as those who continued treatment. Differences in optimal CLBRs were compared using the log-rank test, and hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using Cox regression adjusted for endometrial thickness, maternal body mass index (BMI), number of miscarriages, number of retrieved oocytes, and infertility diagnosis. Adjusted odds ratios (aORs) and 95% CIs for the CLBRs were determined using multivariable logistic regression analyses while adjusting for endometrial thickness, maternal BMI, number of miscarriages, number of retrieved oocytes, and infertility diagnosis. P  < 0.05 was considered to indicate statistical significance.

In conclusion, our study found no significant improvements in the CLBR or other key outcomes for RPL patients undergoing PGT-A compared with conventional IVF/ICSI. Although these results suggest limited advantages of PGT-A, further large-scale studies are needed to validate these findings and explore the potential benefits of PGT-A for specific patient subgroups.

In this study, we found that for RPL patients, the use of PGT-A did not offer a significant advantage over the established IVF/ICSI technique. Although no significant differences were observed in the CLBR, live birth rate, or miscarriage rate between the PGT-A and IVF/ICSI group, PGT-A led to a slight reduction in miscarriage rates in patients aged ≥ 35 years, indicating a potential benefit for this subgroup. In addition, PGT-A increased the time costs associated with achieving a live birth due to the additional procedural steps, such as embryo biopsy and vitrification, involved in the process. No significant differences were observed in perinatal outcomes between the PGT-A and IVF/ICSI groups. In a cohort study of RPL patients in Japan [ 8 ], no significant differences were observed in live birth or miscarriage rates per pregnancy between the PGT-A group (42 patients) and the non-PGT-A group (50 patients). Due to the small sample size, it was not possible to determine the advantages of PGT-A in increasing live birth rates and reducing miscarriage rates for RPL patients. A retrospective study in Poland found no significant differences in the aneuploidy rates of embryos or pregnancy outcomes between RPL patients and those without RPL [ 27 ]. Another study demonstrated that PGT-A reduced miscarriage rates in patients with AMA [ 28 ], which is consistent with the findings of our subgroup analysis. However, no significant differences were observed in perinatal outcomes between the PGT-A and IVF/ICSI groups in our study, corroborating the findings of other studies [ 29 – 31 ]. PGT-A has yet to demonstrate definitive improvements in birth outcomes or in the CLBR, live birth rate, and miscarriage rate in the general population [ 7 , 32 , 33 ]. The findings of a recent systematic review and meta-analysis that evaluated the role of PGT-A in women with unexplained RPL demonstrated its potential benefit in improving clinical pregnancy rates and live birth rates per embryo transfer cycle [ 34 ]. However, some studies included in the meta-analysis did not adjust for important confounding factors such as maternal age, which might have reduced the reliability of the results. Our research found that PGT-A did not increase the clinical pregnancy rate and live birth rate in a single cycle, which might be due to the methodological and sample size limitations. In summary, although the meta-analysis suggested that PGT-A provides potential benefits in selected subgroups of RPL patients, current evidence does not sufficiently support recommending PGT-A for all cases of unexplained RPL. Further high-quality prospective studies are needed to clarify its role. The conservative calculation of the CLBR is limited to the outcomes of the current treatment cycle undertaken by the patients in our centre, excluding the possibility of live births at other therapeutic institutions [ 35 , 36 ]. The optimal CLBR, estimated using the Kaplan–Meier estimator, assumes that the probability of achieving a live birth per cycle is constant for patients who choose to discontinue treatment and those who continue [ 18 ]. However, as noted by Neal et al. [ 37 ], some studies have focused exclusively on the peak live birth rates, potentially introducing bias by overlooking the substantial proportion of patients who may withdraw from the study due to an unfavourable prognosis. Although some studies have shown that PGT-A can increase live birth rates among RPL patients, the exclusion of cycles in which fresh blastocysts were transferred may have introduced bias [ 5 ]. Additionally, PGT-A may prolong the time to achieve pregnancy for RPL patients due to the missed opportunity for fresh embryo transfer [ 38 ]. The lack of a significant increase in the live birth rate in RPL patients who underwent PGT-A may be attributable to the phenomenon of mosaicism. Reports suggest that PGT-A inaccurately characterises the chromosomal makeup of embryos, given the propensity for some to display mosaicism, a condition where cellular clusters with disparate genetic data coexist within a single embryo [ 39 , 40 ]. Cells within mosaic embryos may not be uniformly distributed, leading to misdiagnosis and the exclusion of potentially viable embryos [ 41 , 42 ]. Consequently, a single trophectoderm biopsy may not provide an accurate assessment of mosaicism extent, and the diagnosis of an embryo as mosaic does not preclude the possibility of a successful live birth [ 43 ]. The exclusion of mosaic blastocysts may reduce the pool of embryos eligible for transfer, particularly affecting patients with a limited embryonic supply [ 44 ], thereby limiting their cumulative prospects for live birth. The emergence of aneuploidies could stem from mitotic errors or prolonged cellular division [ 45 ]. As embryogenesis progresses, the integrity of the spindle assembly checkpoint is strengthened, allowing aneuploid cells to progress through mitosis [ 46 ], which may result in autonomous correction and mosaicism [ 47 ]. Thus, the intrinsic mechanisms of natural selection or chromosomal repair pathways may emerge as more effective alternatives to PGT-A [ 8 ]. Although chromosomal abnormalities are recognised as a key factor in miscarriages, they do not singularly account for all such events. Various factors, including anatomical irregularities, immunological challenges, paternal influences, and lifestyle considerations, also contribute to the multifaceted aetiology of miscarriages [ 48 ]. Essentially, non-euploid embryos are unable to maintain implantation in the early stages [ 49 ], leading to implantation failure and early miscarriage. The intent of PGT-A is to mitigate the risks of implantation failure and miscarriage while promoting live births. However, this study underscores the importance of individualised treatment approaches for RPL patients. For instance, patients aged ≥ 35 years or those with a history of chromosomal abnormalities may derive selective benefits from PGT-A, whereas younger patients or those with limited embryos may benefit more from alternative strategies. Consequently, a more comprehensive evaluation, encompassing lifestyle assessment, hormonal profiling, uterine structure examination, coagulation function, and potential immunotherapies, is likely to be more beneficial for patients with recurrent miscarriages [ 50 ]. The probability of a live birth for RPL patients, taking into account maternal age and prior miscarriage history, is estimated at a promising 40–70% [ 51 ]. For RPL patients who test negative for foetal non-euploidy, a watchful waiting approach may be more appropriate than PGT-A, promoting a broader discussion about its clinical applicability. The major strength of this study lies in its consideration of both conservative and optimal CLBRs, providing a nuanced evaluation of PGT-A’s suitability for RPL patients. The dual approach allowed for a more comprehensive estimation of treatment efficacy by accounting for different patient behaviours regarding cycle continuation. The stratified analyses by age and number of miscarriage offer valuable insights into subgroup-specific outcomes, particularly highlighting the potential benefit of PGT-A in cases with AMA. Unlike many previous studies focusing solely on per-transfer outcomes, our study focused on patient-centred endpoints such as the CLBR per oocyte retrieval cycle, which may better reflect real-world clinical decision-making. Furthermore, the exclusive use of single-blastocyst transfer cycles decreased the confounding effects of multiple gestation-related complications and more clearly demonstrated the effect of embryo ploidy status. Importantly, by excluding the transfer of mosaic embryos, this study ensured that the observed outcomes were attributable to euploid embryos alone, thereby enhancing internal validity. However, the retrospective design may have introduced potential selection bias, and the small sample size limits the generalisability of the findings. Larger-scale, prospective studies are needed to confirm our results and better control for confounding variables, such as the heterogeneity between IVF and ICSI protocols. Moreover, it should be noted that there is a dearth of studies providing longitudinal data on the health of offspring born to RPL patients following PGT-A or conventional IVF/ICSI. This represents an important gap in the literature, highlighting the need for future prospective studies to assess long-term outcomes in children conceived through these approaches.

Globally, an estimated 1–2% of women experience recurrent pregnancy loss (RPL) [ 1 ], a condition defined by the European Society of Human Reproduction and Embryology (ESHRE) as the experience of two or more miscarriages [ 1 ]. RPL is a complex clinical issue with multifactorial causes, including genetic, anatomical, endocrine, and immunological factors, which complicate its diagnosis and management. Preimplantation genetic testing for aneuploidy (PGT-A) is a diagnostic procedure that involves taking a biopsy of the trophectoderm layer of blastocysts generated via standard in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) to discern euploid embryos [ 2 ]. Numerous studies have indicated that PGT-A can potentially improve pregnancy and live birth rates, concurrently reducing the likelihood of miscarriage [ 3 – 5 ]. Moreover, it has been linked to an increase in the cumulative live birth rate (CLBR) and a decrease in the number of transfer cycles needed to achieve a live birth [ 6 ]. However, the reported benefits of PGT-A remain inconsistent, particularly when considering different patient populations and clinical contexts. For women with favourable prognoses, evidence from randomised controlled trials indicates that PGT-A does not significantly improve live birth rates [ 7 ]. Meanwhile, for RPL patients, prospective studies have suggested that although PGT-A may reduce the number of transfer cycles required to achieve a live birth, it does not substantially improve the overall live birth rates [ 8 ]. The use of PGT-A remains controversial due to several unresolved issues. Although it is primarily recommended for cases with advanced maternal age (AMA), RPL, or recurrent implantation failure (RIF), critics have highlighted its potential limitations, including procedural risks, high costs, and the possibility of misdiagnosis due to mosaicism in embryos [ 9 ]. Furthermore, ethical concerns have been raised regarding the prioritisation of embryos based solely on genetic testing, which may conflict with patient preferences or cultural values. Many studies have examined the effectiveness of PGT-A in cases with AMA and RIF [ 6 , 8 , 10 , 11 ], but studies addressing RPL are often constrained by their limited scope and narrow focus on the outcomes of initial transfers while ignoring the outcomes of subsequent embryo transfers [ 8 , 12 ]. Considering that numerous patients may require multiple cycles to achieve a live birth [ 13 ], there is an increasing emphasis on the significance of the CLBR [ 7 , 14 ]. According to the ESHRE guidelines, the CLBR, live birth rate, and pregnancy loss rate are crucial outcomes when evaluating treatment strategies in RPL patients [ 1 ]. Additionally, measures such as the conservative CLBR, optimal CLBR, and conditional live birth rate have been proposed to account for potential biases and provide a more comprehensive assessment of treatment outcomes [ 15 – 18 ]. This retrospective study evaluated the comparative effectiveness of PGT-A versus conventional IVF/ICSI in improving the CLBR, time to live birth, and perinatal outcomes in RPL patients. Subgroup analyses based on maternal age and miscarriage frequency were conducted to further explore potential modifiers of treatment efficacy.

Below is the link to the electronic supplementary material. Supplementary Material 1 Supplementary Material 1 Supplementary Material 2 Supplementary Material 2 Supplementary Material 3 Supplementary Material 3 Supplementary Material 4 Supplementary Material 4 Supplementary Material 5 Supplementary Material 5 Supplementary Material 6 Supplementary Material 6 Supplementary Material 7 Supplementary Material 7 Supplementary Material 8 Supplementary Material 8