Live Births After Low Initial β-hCG in IVF Cycles: A Retrospective Cohort Study

Live Births After Low Initial β-hCG in IVF Cycles: A Retrospective Cohort Study | 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 Live Births After Low Initial β-hCG in IVF Cycles: A Retrospective Cohort Study Sierra DiMarco, Kshitija Mundle, Qixuan Li, Ella Huszti, Daphne Arguelles, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8117555/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Mar, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted 11 You are reading this latest preprint version Abstract Background Serum beta-human chorionic gonadotropin (β-hCG) hormone is a well-established biomarker used for pregnancy monitoring and prognosis in in vitro fertilization (IVF) cycles. After embryo transfer, a high serum β-hCG level with a prompt doubling time is typically reassuring, while a low initial β-hCG often leads to counselling around likely impending pregnancy loss and/or ectopic pregnancy. However, the number of patients with low β-hCG who ultimately deliver a live birth is unclear. Methods This is a single-centre retrospective cohort study of IVF pregnancies between January 2019 and December 2022. Serum β-hCG was drawn 14 days post-fertilization. We considered an initial β-hCG ≤ 50 mIU/mL as low. A logistic mixed-effects regression model assessed the odds of live birth for every 10 mIU/mL increase in β-hCG, adjusting for patient and cycle characteristics (age, body mass index, embryo stage, number of embryos transferred, and preimplantation genetic testing for aneuploidy). Receiver operating characteristic curves were plotted to determine optimal cut-points. Results Among 2443 pregnancies, the prevalence of live birth was 12% for those with an initial β-hCG ≤ 50 mIU/mL. For each 10 mIU/mL difference in initial β-hCG, the odds of live birth increased significantly (aOR = 1.035, 95% CI: 1.027, 1.042). Receiver operating characteristic curve analysis showed that an initial β-hCG greater than 22.5 mIU/mL identified over 99% of patients who ultimately had a live birth (sensitivity 1, specificity 0.21, AUC 0.726). The rate of change from initial β-hCG demonstrated stronger discriminatory performance for live birth among patients with low initial β-hCG (AUC 0.876 [0.84, 0.91]) than among those with an initial β-hCG > 50 mIU/mL (AUC 0.584 [0.56, 0.61]). Conclusions While IVF pregnancies with a low initial β-hCG can result in live birth, the likelihood is low. The rate of β-hCG rise emerged as a stronger discriminator of pregnancy outcomes when the initial β-hCG is low. Live birth was extremely rare when the initial β-hCG was below 22.5 mIU/mL. These findings offer prognostic data to guide counselling and refine expectations after IVF. IVF β-hCG live birth early pregnancy embryo transfer ICSI PGT-A pregnancy prognosis Figures Figure 1 Background The emotional, physical, and financial burden of in vitro fertilization (IVF) often leaves patients in a state of stress surrounding the outcome of their treatment [ 1 ]. When compared to unassisted pregnancies, patients who conceive through IVF exhibit higher levels of anxiety and depression symptoms [ 2 – 5 ]. Anxiety tends to increase with each stage, with the highest levels observed after embryo transfer to the pregnancy test [ 6 , 7 ]. Effective counselling is imperative for patient well-being, particularly for patients undergoing fertility treatments [ 8 ]. Providing information on the prognosis can prepare patients for adverse outcomes and allow them to make an informed decision about the pregnancy. Serum beta-human chorionic gonadotropin (β-hCG) hormone is a well-supported biomarker used for pregnancy testing, monitoring, and prognosis. After a successful embryo transfer and implantation, the syncytial trophoblast of the growing placenta begins to secrete β-hCG, which can be detected in the patient’s serum to confirm the pregnancy. If positive, serial β-hCG levels will be evaluated for quantity and trend as these levels provide important information about the development of the pregnancy. It is widely acknowledged that higher β-hCG levels are correlated with positive pregnancy outcomes [ 9 – 14 ]. Clinicians are currently using β-hCG levels to counsel patients on the likelihood of a live birth, particularly when the initial level is high. Comparatively, numerous studies have described a β-hCG cut-off point below which the prognosis for live birth is poor [ 15 , 16 ]. The literature lacks well-defined statistics on the prevalence of live birth following a low initial serum β-hCG and how to interpret the trend of β-hCG rise in this context. This ambiguity presents a challenge in patient counselling and decision-making in IVF treatments. At Mount Sinai Fertility (MSF), patients with an initial β-hCG ≤ 50 mIU/mL are typically counselled that their pregnancy is unlikely to be viable and to monitor for signs and symptoms of pregnancy loss and ectopic pregnancy. Due to the lack of data published in the literature, patients cannot be provided with a reliable prognosis for a healthy pregnancy when their initial level is low. Therefore, our objective was to determine the prevalence of live births after IVF with a low initial β-hCG and to identify β-hCG patterns associated with a very low likelihood of live birth. This can inform patient counselling and prevent unnecessary intervention in viable and wanted pregnancies. Unlike existing studies that focus on a single cycle type, we considered both fresh and frozen cycles, as well as cycles that employed preimplantation genetic testing for aneuploidy (PGT-A). We identified patient and cycle characteristics that increase the likelihood of a positive pregnancy outcome. Methods We conducted a single-centre retrospective cohort study of all pregnancies conceived following in vitro fertilization (IVF) between January 2019 and December 2022 at Mount Sinai Fertility, Toronto, Canada. Research ethics approval was granted by the Mount Sinai Hospital Research Ethics Board (23-0054-C). Study population Patients who achieved pregnancy, defined by a positive β-hCG (≥ 3 mIU/mL), after a frozen or fresh embryo transfer cycle were included. Both autologous and donor oocyte conceptions were included. If patients had more than one pregnancy within the timeframe, each pregnancy was assessed and recorded individually. Exclusion criteria encompassed patients who did not undergo embryo transfer and those with an undetectable β-hCG post-transfer. Demographic data were collected from the patient’s electronic medical record, including age at oocyte retrieval, body mass index (BMI), reason for IVF treatment, gravidity, parity, and duration of infertility in months. Cycle characteristics collected were fresh or frozen embryo, method of fertilization (conventional IVF vs. intracytoplasmic sperm injection (ICSI), endometrial preparation protocol, number of embryos transferred, use of preimplantation genetic testing for aneuploidy (PGT-A), and developmental stage of embryo transfer (cleavage stage or blastocyst day 5–7). These variables were selected based on clinical relevance and existing literature demonstrating their association with live birth outcomes [ 17 , 18 ]. Serum β-hCG levels were drawn at 14 days post-fertilization. A low initial serum β-hCG was defined as ≤ 50 mIU/mL, consistent with the lowest thresholds commonly reported in the literature [ 9 , 13 , 19 – 21 ]. Serum β-hCG was measured at our internal laboratory, with a small number of tests performed externally. Definitions of pregnancy outcomes Reproductive outcomes included biochemical pregnancy loss: the spontaneous decrease in β-hCG before confirmation by ultrasound or histopathology; clinical pregnancy loss: ultrasound or histopathologic confirmation of a gestational sac; ectopic pregnancy: implantation outside of the uterus; resolved pregnancy of unknown location: resolved elevated β-hCG without visualization of the gestation inside the uterus; therapeutic abortion: termination of pregnancy; and ongoing clinical pregnancy: pregnancy at 10 weeks’ gestation with ultrasound confirmation of fetal heartbeat. Birth data were sourced from the Better Outcomes Registry & Network (BORN) Ontario, with pregnancy outcomes categorized into live birth term delivery, live birth preterm delivery, late clinical pregnancy loss, and intrauterine fetal demise. Live births were defined as delivery of a fetus after 20 weeks’ gestation with confirmation of life, with term gestation reflecting birth after 37 weeks. Late clinical pregnancy loss was defined as spontaneous abortion after 10 weeks of gestation. Intrauterine fetal demise was defined as the loss of a fetus after 20 weeks’ gestation. Sonographic information was collected, including the number of gestational sacs, the number of embryos detected, and the number of fetal heartbeats. The primary outcome of the study was live birth. Statistical Analysis Patient and cycle characteristics were analyzed using means with standard deviations or medians and interquartile ranges for continuous variables, and frequencies and percentages for categorical variables. Univariable and multivariable logistic mixed-effects regression models were created to determine the association between patient and cycle factors and live birth outcomes, with results reported as odds ratios (OR) with 95% confidence intervals and p-values (significance at p < 0.05). Receiver operating characteristic (ROC) curves were generated to evaluate the discriminatory performance of both the initial β-hCG levels and the trend of β-hCG levels for live birth outcomes. For each analysis, sensitivity, specificity, positive predictive value and negative predictive value were calculated, and cut-points were defined using the Youden index to optimize the balance of sensitivity and specificity, with an additional cut-point selected to maximize sensitivity. The area under the curve (AUC) with interquartile ranges was calculated to assess diagnostic accuracy, with an area of 1.00 indicating a perfect test. Results Patient Characteristics The median age at the time of egg retrieval was 34.0 [31.0, 37.0]. The median BMI was 24.5kg/m² [21.6, 28.2]. Patients reported several reasons for seeking IVF treatment, the most common of which were male factor (28.7%), unexplained infertility (21.2%), and advanced maternal age (16.7%) (Table 1 ). [Insert Table 1 here] Table 1 Characteristics of study population from MSF who underwent IVF between January 2019 and December 2022 Characteristic Categories Cohort (n) 2443 Patient's age at time of egg retrieval, median years [IQR] a 34.0 [31.0, 37.0] BMI, median kg/m² [IQR] b 24.5 [21.6, 28.2] Oocyte source, n (%) Autologous 2140 (87.6) Donor 274 (11.2) Reciprocal IVF 29 (1.19) Obstetric history, median n [IQR] Gravidity 1.00 [0.00, 2.00] Parity 0.00 [0.00, 1.00] Prior pregnancy losses 0.00 [0.00, 1.00] Duration of infertility, median months [IQR] 19.0 [9.00, 32.0] Reasons for seeking treatment, n (%) Male factor 702 (28.7) Unexplained infertility 608 (24.9) Advanced female age 518 (21.2) Diminished ovarian reserve 408 (16.7) Tubal factor 255 (10.4) Polycystic ovary syndrome (PCOS) 238 (9.74) Endometriosis 194 (7.94) No male partner 128 (5.24) Insemination method, n (%) Conventional IVF 806 (33.0) ICSI 1631 (66.8) IVF and ICSI 6 (0.25) Embryo transfer type, n (%) Frozen 1897 (77.7) Fresh 546 (22.4) Endometrial preparation, n (%) Ovulatory FET 367 (15.0) Programmed FET 1485 (60.7) Modified ovulatory FET 45 (1.84) Fresh embryo transfer 546 (22.3) PGT-A performed, n (%) 624 (25.5) PGT-A result of transferred embryo, n (%) Euploid 601 (96.3) Mosaic 13 (2.08) No DNA 8 (1.28) Inconclusive 2 (0.32) Stage of embryo transfer, n (%) Cleavage 88 (3.60) Blastocyst day 5 1678 (68.7) Blastocyst day 6 642 (26.3) Blastocyst day 7 21 (0.86) Blastocysts day 5 and 6 13 (0.53) Blastocysts day 6 and 7 1 (0.04) Embryos transferred, n (%) Single embryo transfer 2185 (89.4) Double embryo transfer 257 (10.5) Triple embryo transfer 1 (0.04) Initial serum β-hCG, median mIU/mL [IQR] 130 [65.0, 216] a Missing age from 9 patients (0.37%) b Missing BMI from 129 patients (5.28%) BMI, body mass index; FET, frozen embryo transfer; ICSI, intracytoplasmic sperm injection; IQR, interquartile range; IVF, in vitro fertilization; PGT-A, preimplantation genetic testing for aneuploidy. Cycle Parameters In our cohort, the majority of patients (2140; 87.6%) used autologous oocytes for embryo transfer, while 274 patients used donor oocytes (11.2%) and 29 patients used reciprocal IVF oocytes (1.19%). 1897 (77.7%) patients underwent frozen embryo transfer, and 546 (22.4%) underwent fresh transfer. Among transferred embryos, 1678 (68.7%) were day 5 blastocysts, 642 (26.3%) day 6 blastocysts, 21 (0.86%) day 7 blastocysts, and 88 (3.60%) were at the cleavage stage. There were 624 (25.5%) embryos screened with PGT-A before transfer. The full results are presented in Table 1 . Pregnancy Outcomes The median initial β-hCG level was 130 mIU/mL [65.0, 216]. Initial β-hCG was intended to be collected at 14 days post-fertilization; the vast majority of the patient population followed this standardized collection time. Out of the 2443 embryo transfers, 1575 pregnancies (64.5%) were ongoing at or beyond 10 weeks’ gestation (Table 2 ). The remaining pregnancies resulted in biochemical pregnancy loss (483, 19.8%), clinical pregnancy loss (321, 13.1%), resolved pregnancy of unknown location (41, 1.68%), or ectopic pregnancy (18, 0.74%). Among the 1575 ongoing pregnancies, 1179 (74.6%) resulted in a live term delivery (≥ 37 weeks’ gestation), 133 (8.42%) in a live preterm delivery (< 37 weeks’ gestation), and 27 (1.71%) in a live birth of unknown gestational age. There were 132 (5.40%) with unknown outcomes beyond 10 weeks’ gestation, mainly due to incomplete delivery data in the BORN Ontario after discharge from the MSF clinic at 10 weeks or delivery outside Ontario, Canada. Pregnancy outcomes are reflected in Table 2 . Table 2 Pregnancy outcomes at 10 weeks and delivery for patients stratified by initial serum β-hCG levels Characteristic Categories All study pregnancies Pregnancies with initial serum β-hCG levels ≤ 50 mIU/mL Pregnancies with initial serum β-hCG levels > 50 mIU/mL Pregnancies with initial serum β-hCG levels > 50 mIU/mL and multiple gestations (n) 2443 491 1952 53 Pregnancy outcome at 10 weeks’ gestation, n (%) Biochemical pregnancy loss 483 (19.8) 320 (65.2) 163 (8.35) Clinical pregnancy loss 321 (13.1) 70 (14.3) 251 (12.9) Ectopic pregnancy loss 18 (0.74) 13 (2.65) 5 (0.26) Ongoing pregnancy 1512 (61.9) 76 (15.5) 1436 (73.6) Resolved pregnancy of unknown location 41 (1.68) 12 (2.44) 29 (1.49) Vanishing twin ongoing pregnancy 10 (0.41) - 10 (0.51) Viable twin gestation 51 (2.09) - 51 (2.61) Viable triplet gestation 2 (0.08) - 2 (0.10) Unknown outcomes 5 (0.20) - 5 (0.26) Pregnancy outcome at delivery, n (%) Live birth term delivery (> 37 weeks) 1179 (48.3) 50 (10.2) 1129 (57.8) 17 (32.1) Live birth preterm delivery ( 10 weeks’ gestation, 20 weeks’ gestation) 24 (0.98) 3 (0.61) 21 (1.08) 2 (3.77) Therapeutic abortion 16 (0.66) 1 (0.20) 15 (0.77) - Unknown outcomes 132 (5.40) 8 (1.63) 124 (6.35) 7 (13.2) Pregnancy Outcomes by Initial β-hCG levels Among patients with an initial β-hCG between 3–50 mIU/mL (n = 491), the most frequent outcome was biochemical pregnancy loss, affecting 65.2% (n = 320) of the group (Table 2 ). Clinical pregnancy losses occurred in 70 patients (14.3%), resolved pregnancy of unknown location in 12 patients (2.44%) and ectopic pregnancy in 13 patients (2.65%). Final pregnancy outcomes were available for 98% (n = 483) of patients with a low initial β-hCG; of these, the prevalence of live birth was 12% with 58 patients delivering live infants. The prevalence of ectopic pregnancies was disproportionately represented in lower β-hCG ranges. Of the 18 total ectopic pregnancies, 13 (72%) had an initial β-hCG ≤ 50 mIU/mL, and 16 (89%) were < 100 mIU/mL. Additionally, 61% (11/18) of ectopic cases involved patients aged 35 years or older. Only one ectopic case involved a euploid embryo. Logistic Mixed-Effects Models Predicting Live Birth Both univariable and multivariable logistic mixed-effect regression models were used to identify predictors of live birth. With each 10 unit (mIU/mL) greater initial serum β-hCG, there was a statistically significant increase in the odds of live birth by 3.5%, OR = 1.04, 95% CI [1.03, 1.04], after adjusting for age, BMI, stage of transfer, number of embryos transferred and use of PGT-A. A positive β-hCG after transfer of a euploid embryo conferred more than twice the odds of live birth compared to untested embryos, OR = 2.24, 95% CI [1.82, 2.76]. Slower growing blastocyst transfer (day 6 and day 7) significantly lowered odds of live birth compared to day 5 blastocysts, even after adjustment (Day 6: OR = 0.70, 95% CI [0.57, 0.85]; Day 7: OR = 0.26, 95% CI [0.09, 0.74]). Lastly, the number of embryos transferred was inversely correlated with live birth (OR = 0.44, 95% CI [0.39, 0.51]). Age at oocyte retrieval, BMI and cleavage-stage transfers were not significant predictors in the multivariable models (p > 0.05). Results from logistic mixed-effects models are presented in Table 3 . Table 3 Univariable and multivariable logistic mixed-effects models evaluating predictors of live birth Predictor Univariable Multivariable OR 95% CI OR 95% CI Initial serum β-hCG (per 10 units) 1.04 1.03, 1.04 1.04 1.03, 1.04 Age at egg retrieval (years) 0.99 0.97, 1.00 1.00 0.98, 1.01 BMI (kg/m²) 0.97 0.96, 0.99 1.00 0.98, 1.01 Stage: Blastocyst day 5 (Reference) 1.00 1.00 Stage: Blastocyst day 6 0.76 0.63, 0.91 0.7 0.57, 0.85 Stage: Blastocyst day 7 0.26 0.09, 0.72 0.26 0.09, 0.74 Stage: Cleavage 0.64 0.41, 0.99 1.10 0.69, 1.74 Number of embryos transferred 0.37 0.28, 0.49 0.44 0.39, 0.51 PGT-A (Yes) 2.37 1.95, 2.89 2.24 1.82, 2.76 Receiver Operating Characteristic (ROC) Curve Analysis The ROC curve analysis was conducted to evaluate the discriminatory performance of initial β-hCG for live birth outcomes. The area under the curve (AUC) was 0.726 (95% CI [0.705, 0.746]), indicating acceptable discrimination between live birth and no live birth. The optimal threshold that balances sensitivity and specificity using the Youden index was an initial β-hCG of 100.5 mIU/mL (sensitivity 0.79, specificity 0.57). A secondary logistic mixed-effects analysis using β-hCG above this threshold showed significantly increased odds of live birth, after adjusting for patient and cycle characteristics (OR = 5.18, 95% CI [4.14, 6.47]) (Supplementary data). This corresponds to a 418% increase. To characterize β-hCG values below which live birth was uncommon, we performed ROC analysis prioritizing maximal sensitivity (1.00). This analysis indicated that more than 99% of live births occurred above an initial β-hCG of 22.5 mIU/mL with a NPV of 97.6%. The rate of change from initial β-hCG provided greater discriminatory value among patients with low initial β-hCG (AUC 0.876 [0.84, 0.91]) compared to those with an initial β-hCG > 50 mIU/mL (AUC 0.584 [0.56, 0.61]). In the low initial β-hCG subgroup, the optimal threshold of 44% daily increase resulted in significantly stronger specificity (0.72) and negative predictive value (0.99), compared to the optimal threshold of 46% in the > 50 mIU/mL subgroup (specificity 0.25, negative predictive value 0.70). The ROC curves are presented in Fig. 1 . [Insert Fig. 1 here] Discussion A clear understanding of the prognosis associated with a low initial β-hCG is essential for early pregnancy counselling. In this retrospective analysis, among the 491 patients with an initial β-hCG level ≤ 50 mIU/mL, the prevalence of live births was 12%, resulting in 50 term and eight preterm births. The lowest level that resulted in a live birth was 6 mIU/mL, measured 14 days post-fertilization, which tripled in 48 hours. Several studies have also documented live births from IVF despite very low initial β-hCG [ 22 , 23 ]. In one large retrospective cohort study, three cases of live births were reported with initial β-hCG levels of 5, 6, and 8 mIU/mL [ 14 ]. Our results demonstrate that pregnancies with a low initial β-hCG have the potential to result in a live birth. Interestingly, we found a higher proportion of ectopic pregnancies among the low β-hCG group compared to the high β-hCG group (2.65% vs 0.26%). However, none of these cases had significant risk factors for ectopic pregnancy (e.g. tubal disease, prior ectopic pregnancy). These findings underscore the importance of vigilant follow-up when early hormone levels are low. PGT-A is widely recognized for its role in selecting viable embryos and reducing the risk of pregnancy loss [ 24 ]. Our study uniquely included PGT-A in the multivariable model for live birth. While the initial β-hCG remained a significant predictor, the transfer of a PGT-A-tested euploid embryo was independently associated with live birth after adjusting for early β-hCG levels. In our cohort, the use of a euploid embryo more than doubled the odds of live birth. Therefore, the advantage associated with PGT-A is not entirely captured by the initial hormone level. Similarly, our analysis revealed that day-5 blastocyst transfers were associated with increased odds of live birth compared with cleavage-stage or day-6 and day-7 blastocyst transfers, which is consistent with prior studies [ 10 , 20 , 25 ]. Of the 58 live births with a low initial β-hCG, over half of them were blastocyst day-5 transfers and only three cycles were transferred at the cleavage stage. In addition to the timing of transfer, we found that the increase in the number of embryos transferred was associated with a decrease in the odds of a live birth. Our result is likely attributable to confounding by indication; patients with advanced reproductive age or a history of recurrent implantation failure are more likely to undergo multiple embryo transfers, although they are also at a poorer prognosis [ 26 ]. Younger maternal age was associated with increased odds of live birth, although this association was not statistically significant. Patients with a low initial β-hCG were modestly older (34.40 ± 4.64 vs. 33.79 ± 4.60 years). In addition, advanced maternal age (≥ 40 years) was more prevalent among those with pregnancy loss at 10 weeks’ gestation, in both low and high initial β-hCG groups. This is in agreement with the literature on the impact of advanced maternal age [ 27 ]. A lower BMI appeared predictive of a live birth; however, after adjusting for other cycle and patient characteristics, its statistical significance was lost. In line with previous studies [ 28 , 29 ], among pregnancies that resulted in live births, we found that the mean maternal BMI was higher in those with a low initial β-hCG (28.22 ± 6.77 kg/m²) compared with those with a high initial β-hCG (25.09 ± 5.07 kg/m²). In our study, patient characteristics were associated with live birth rates in the univariable analysis, but only cycle characteristics remained significant in the multivariable model. As expected, the initial serum β-hCG was predictive of a positive pregnancy outcome; for each 10-unit greater initial β-hCG, there was a statistically significant increase in live birth rates, while adjusting for patient and cycle characteristics. Our ROC curve identified 100.5 mIU/mL (AUC 0.726) as the optimal cut-point with the greatest sensitivity and specificity for predicting live birth. Among patients with an initial β-hCG above this value, 66.4% delivered. The reliability of a high initial β-hCG in predicting positive pregnancy outcomes has been well supported [ 15 , 19 ]. The 100.5 mIU/mL level is comparable to that in the literature, with a similar sensitivity (~ 80%) [ 13 , 23 , 25 ]. The utility of a single time-point threshold for predicting positive pregnancy outcomes is limited because a range of β-hCG collection days is reported in the literature. Our study confirms live births can occur with β-hCG well below those thresholds. To better reflect the observed prevalence of live births after a low initial β-hCG, we explored a model that prioritized sensitivity. An initial β-hCG of 22.5 mIU/mL captured over 99% of patients who ultimately had a live birth. Although this value should not be interpreted as a clinical threshold, it provides valuable context for counselling patients with low initial β-hCG. Live birth was extremely uncommon below this level, underscoring the low likelihood of viability. There is a lot of ambiguity regarding the prognosis of these pregnancies, with some recommending discontinuing luteal phase support if the initial β-hCG < 58.8 mIU/mL [ 21 ]. Our findings identify a β-hCG level with a wider catchment for live births to minimize the risk of incorrectly dismissing viable pregnancies. The trajectory of β-hCG rise also has prognostic relevance, beyond the absolute initial level. The doubling time of β-hCG is a well-established predictor of live birth [ 15 , 23 , 30 ]. Unique to previous studies, we performed an ROC subgroup analysis on two distinct ranges of β-hCG values. The rate of change from initial β-hCG was a stronger discriminator of live birth among patients with an initial serum β-hCG ≤ 50 mIU/mL (AUC 0.876 [0.84, 0.91]) than among those with an initial β-hCG > 50 mIU/mL (AUC 0.584 [0.56, 0.61]). In the low initial β-hCG subgroup, 99% of patients who did not meet the optimal 44% daily increase of β-hCG did not deliver a live birth. In comparison to the β-hCG > 50 mIU/mL subgroup, where only 70% of patients who did not meet the 46% threshold failed to deliver. There were no cases of live births after a decline in β-hCG. To our knowledge, this is the first study to demonstrate that the discriminatory performance of β-hCG rise is significantly greater in patients with initially low levels. Prior research has also highlighted the discriminatory value of β-hCG dynamics, with suggested thresholds of at least a 53% rise [ 15 ] or a 1.9-fold increase [ 21 ] in 48 hours. Our findings align with the POPI-Plus study, a predictive clinical model for live birth [ 30 ]. The authors found that a greater 48-hour rise was required to achieve the same live birth probability when the initial β-hCG level was lower, reflecting underlying physiologic variability. Our study has several limitations. Although initial β-hCG was intended to be collected at a standardized time point, minor deviations in the collection day occurred. This may introduce differences in absolute values, which can limit its interpretation. Most β-hCG measurements were performed in our internal laboratory, but a minority were completed at external laboratories. This may introduce some inter-laboratory variation. We also did not collect any data on the morphologic quality of embryos and their correlation with live birth outcomes. Finally, as a retrospective single-centre study, our findings may be influenced by practice patterns at our institution and should be validated across diverse clinical settings. These findings are specific to pregnancies conceived via IVF/ICSI and may not be generalizable to spontaneous conceptions or other forms of assisted reproductive technology. Conclusions Patients with detectable but low β-hCG levels represent a vulnerable population. There is less known about their prognosis because, despite increased prevalence of adverse outcomes, there are cases of live births after remarkably low levels. This poses a challenge to clinicians when counselling patients in this group. Patients often hold unrealistic expectations when starting IVF [ 31 – 33 ]. Managing expectations with objective information has been shown to reduce feelings of distress and anxiety, and aid in informed decision-making for the current cycle and subsequent cycles [ 34 ]. Our study demonstrates a 12% prevalence of live birth rates in this group, providing valuable information for setting patient expectations. By identifying 22.5 mIU/mL as a level that captured nearly all viable pregnancies, we were able to distinguish two subgroups of patients with a low initial β-hCG. This distinction supports more individualized prognostic counselling, as outcomes differ significantly between these groups. Notably, the use of a euploid embryo should inform counselling, as we saw the advantage of PGT-A is not entirely captured by the initial β-hCG level. Finally, we are able to demonstrate the unique impact of the rate of β-hCG rise on positive outcomes in this population. Our focus on live birth among patients with an initially low β-hCG was to increase transparency and address patients’ calls for greater clarity in this unfamiliar process [ 35 – 37 ]. In conclusion, our study contributes to growing evidence that a single low β-hCG value should be interpreted with careful consideration. Future directions should aim to validate our results in a multi-centre study. Abbreviations Abbreviation Meaning Page AUC Area under the curve 4 β-hCG beta-human chorionic gonadotropin 2 BMI Body mass index 2 BORN Better Outcomes Registry & Network 4 ICSI Intracytoplasmic sperm injection 4 IVF In vitro fertilization 3 MSF Mount Sinai Fertility 3 OR Odds ratios 4 PGT-A Preimplantation genetic testing for aneuploidy 2 ROC Receiver operating characteristic 2 Declarations Ethics approval and consent to participate This retrospective study was approved by the Mount Sinai Hospital Research Ethics Board (IRB #23-0054-C), which granted a waiver of informed consent due to the use of de-identified clinical data. Consent for publication Not applicable. Availability of data and materials All data supporting the findings of this study are included in this article and its supplementary file. The patient-level dataset cannot be shared publicly due to institutional and ethical restrictions. Fully de-identified data may be made available from the corresponding author upon reasonable request and with approval from the Mount Sinai Hospital Research Ethics Board. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions S.D and V.B conceptualized and designed the study. S.D, K.M, and D.A completed data extraction and preliminary analysis. Q.L and E.H conducted statistical analysis. S.D, K.M, and D.A wrote the manuscript under the guidance of V.B. All authors read the final draft and approved its submission for publication. Acknowledgements Not applicable Authors' information Sierra DiMarco is a medical student at Queen’s University with a Masters of Biomedical Science from the University of Guelph. With training in assisted reproductive biotechnologies, her clinical interest is reproductive endocrinology and early pregnancy outcomes. Her current research focuses on prognosis after IVF and enhancing patient-centred counselling. References Paraskevi L, Antigoni S, Kleanthi G. Stress and Anxiety Levels in Couples who Undergo Fertility Treatment: a Review of Systematic Reviews. Mater Sociomed. 2021;33:60–4. doi:10.5455/msm.2021.33.60-64. Cozzolino M, Troiano G, Coccia ME. Spontaneous pregnancy versus assisted reproductive technologies: implications on maternal mental health. Women Health. 2021;61:303–12. doi:10.1080/03630242.2021.1881025. Hammarberg K, Rowe HJR, Fisher JRW. Early post-partum adjustment and admission to parenting services in Victoria, Australia after assisted conception. Hum Reprod. 2009;24:2801–9. doi:10.1093/humrep/dep282. Li N, Bai J, Wang L, Chen M, Zhu H, Dong J, et al. 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Kahyaoğlu İ, Demir B, Ertürk Aksaka S, Kaplanoğlu İ, Mollamahmutoğlu L. Value of Post-transfer Day-12 Beta Human Chorionic Gonadotropin Levels for Pregnancy Outcome Prediction of Intracytoplasmic Sperm Injection Cycles. Balkan Med J. 2017;34:450–7. doi:10.4274/balkanmedj.2016.1769. Papageorgiou TC, Leondires MP, Miller BT, Chang AS, Armstrong AB, Scott LA, et al. Human chorionic gonadotropin levels after blastocyst transfer are highly predictive of pregnancy outcome. Fertil Steril. 2001;76:981–7. doi:10.1016/S0015-0282(01)02840-0. Poikkeus P, Hiilesmaa V, Tiitinen A. Serum HCG 12 days after embryo transfer in predicting pregnancy outcome. Hum Reprod. 2002;17:1901–5. doi:10.1093/humrep/17.7.1901. Singh N, Goyal M, Malhotra N, Tiwari A, Badiger S. Predictive value of early serum beta-human chorionic gonadotrophin for the successful outcome in women undergoing in vitro fertilization. J Hum Reprod Sci. 2013;6:245–7. doi:10.4103/0974-1208.126291. Sung N, Kwak-Kim J, Koo HS, Yang KM. Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle. J Assist Reprod Genet. 2016;33:1185–94. doi:10.1007/s10815-016-0744-y. Shamonki MI, Frattarelli JL, Bergh PA, Scott RT. Logarithmic curves depicting initial level and rise of serum beta human chorionic gonadotropin and live delivery outcomes with in vitro fertilization: An analysis of 6021 pregnancies. Fertil Steril. 2009;91:1760–4. doi:10.1016/j.fertnstert.2008.02.171. Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic Patients With an Early Viable Intrauterine Pregnancy: hCG Curves Redefined. Obstet Gynecol. 2004;104:50. doi:10.1097/01.AOG.0000128174.48843.12. Chung K, Sammel MD, Coutifaris C, Chalian R, Lin K, Castelbaum AJ, et al. Defining the rise of serum HCG in viable pregnancies achieved through use of IVF. Hum Reprod. 2006;21:823–8. doi:10.1093/humrep/dei389. McLernon DJ, Steyerberg EW, Te Velde ER, Lee AJ, Bhattacharya S. Predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation: population based study of linked cycle data from 113 873 women. BMJ. 2016;:i5735. doi:10.1136/bmj.i5735. Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018;378:126–36. doi:10.1056/NEJMoa1705334. Bjercke S, Tanbo T, Dale PO, Mørkrid L, Åbyholm T. Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization. Hum Reprod. 1999;14:1642–6. doi:10.1093/humrep/14.6.1642. Oron G, Esh-Broder E, Son W-Y, Holzer H, Tulandi T. Predictive value of maternal serum human chorionic gonadotropin levels in pregnancies achieved by in vitro fertilization with single cleavage and single blastocyst embryo transfers. Fertil Steril. 2015;103:1526-1531.e1-2. doi:10.1016/j.fertnstert.2015.02.028. Wu Y, Liu H. Possibility of live birth in patients with low serum β-hCG 14 days after blastocyst transfer. J Ovarian Res. 2020;13:132. doi:10.1186/s13048-020-00732-6. Burks HR, Baker M, Quaas AM, Bendikson KA, Chung K, Paulson RJ. The dilemma of counseling patients about poor prognosis: live birth after IVF with autologous oocytes in a 43-year-old woman with FSH levels above 30 mIU/mL. J Assist Reprod Genet. 2017;34:1185–8. doi:10.1007/s10815-017-0986-3. Hughes LM, Schuler A, Sharmuk M, Schauer JM, Pavone ME, Bernardi LA. Early β-hCG levels predict live birth after single embryo transfer. J Assist Reprod Genet. 2022;39:2355–64. doi:10.1007/s10815-022-02606-w. 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. Hum Reprod. 2021;36:2339–44. doi:10.1093/humrep/deab117. Kathiresan ASQ, Cruz-Almeida Y, Barrionuevo MJ, Maxson WS, Hoffman DI, Weitzman VN, et al. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fertil Steril. 2011;96:1362–6. doi:10.1016/j.fertnstert.2011.09.042. ESHRE Guideline Group on the Number of Embryos to Transfer, Alteri A, Arroyo G, Baccino G, Craciunas L, De Geyter C, et al. ESHRE guideline: number of embryos to transfer during IVF/ICSI†. Hum Reprod. 2024;39:647–57. doi:10.1093/humrep/deae010. Lean SC, Derricott H, Jones RL, Heazell AEP. Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis. PLoS One. 2017;12:e0186287. doi:10.1371/journal.pone.0186287. Brady PC, Farland LV, Ginsburg ES. Serum Human Chorionic Gonadotropin Among Women With and Without Obesity After Single Embryo Transfers. J Clin Endocrinol Metab. 2018;103:4209–15. doi:10.1210/jc.2018-01057. Eskild A, Fedorcsak P, Mørkrid L, Tanbo TG. Maternal body mass index and serum concentrations of human chorionic gonadotropin in very early pregnancy. Fertil Steril. 2012;98:905–10. doi:10.1016/j.fertnstert.2012.06.011. Mourad A, Antaki R, Rowen M, Lévesque É, Lapensée L. The POPI-Plus tool: prediction model of outcome of pregnancy in in vitro fertilization from a large retrospective cohort. Fertil Steril. 2024;121:489–96. doi:10.1016/j.fertnstert.2023.11.035. Copp T, Kvesic D, Lieberman D, Bateson D, McCaffery KJ. ‘Your hopes can run away with your realistic expectations’: a qualitative study of women and men’s decision-making when undergoing multiple cycles of IVF. Hum Reprod Open. 2020;2020:hoaa059. doi:10.1093/hropen/hoaa059. Fauser BCJM, Boivin J, Barri PN, Tarlatzis BC, Schmidt L, Levy-Toledano R. Beliefs, attitudes and funding of assisted reproductive technology: Public perception of over 6,000 respondents from 6 European countries. PLoS One. 2019;14:e0211150. doi:10.1371/journal.pone.0211150. Wyndham N, Marin Figueira PG, Patrizio P. A persistent misperception: assisted reproductive technology can reverse the “aged biological clock.” Fertil Steril. 2012;97:1044–7. doi:10.1016/j.fertnstert.2012.02.015. Gonda KJ, Domar AD, Gleicher N, Marrs RP. Insights from clinical experience in treating IVF poor responders. Reprod Biomed Online. 2018;36:12–9. doi:10.1016/j.rbmo.2017.09.016. Dancet EAF, Nelen WLDM, Sermeus W, De Leeuw L, Kremer JAM, D’Hooghe TM. The patients’ perspective on fertility care: a systematic review. Hum Reprod Update. 2010;16:467–87. doI:10.1093/humupd/dmq004. Harrison C, Gameiro S, Boivin J. Patient willingness, preferences and decision-making about planning for three complete cycles of IVF/ICSI treatment. Hum Reprod. 2021;36:1339–52. doi:10.1093/humrep/deab040. Sousa-Leite M, Costa R, Figueiredo B, Gameiro S. Discussing the possibility of fertility treatment being unsuccessful as part of routine care offered at clinics: patients’ experiences, willingness, and preferences. Hum Reprod. 2023;38:1332–44. doi:10.1093/humrep/dead096. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialLiveBirthsAfterLowInitialhCGBMCPregnancyChildbirth.docx Cite Share Download PDF Status: Published Journal Publication published 18 Mar, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 20 Feb, 2026 Reviews received at journal 17 Feb, 2026 Reviewers agreed at journal 16 Feb, 2026 Reviews received at journal 20 Jan, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviewers invited by journal 01 Dec, 2025 Editor invited by journal 17 Nov, 2025 Editor assigned by journal 15 Nov, 2025 Submission checks completed at journal 15 Nov, 2025 First submitted to journal 14 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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15:04:36","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":135758,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8117555/v1/64ae7a5b6678c81cb4b9daaf.html"},{"id":97369025,"identity":"7bf8b441-dda0-48ae-9142-ac1a9e304b59","added_by":"auto","created_at":"2025-12-03 16:23:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":243793,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curves for initial β-hCG and β-hCG rise in predicting live birth\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis figure presents four ROC curves illustrating the discriminatory ability of β-hCG measures for live birth outcomes.\u003c/p\u003e\n\u003cp\u003e(A) ROC curve for live birth: initial β-hCG (full cohort) (Threshold = Youden optimal cut off).\u003c/p\u003e\n\u003cp\u003e(B) ROC curve maximizing sensitivity for live birth: initial β-hCG (full cohort).\u003c/p\u003e\n\u003cp\u003e(C) ROC curve for live birth: rate of change in β-hCG (initial ≤50 mIU/mL).\u003c/p\u003e\n\u003cp\u003e(D) ROC curve for live birth: rate of change in β-hCG (initial \u0026gt; 50 mIU/mL).\u003c/p\u003e","description":"","filename":"Figure1LiveBirthsAfterLowInitialhCGBMCPregnancyChildbirth.png","url":"https://assets-eu.researchsquare.com/files/rs-8117555/v1/c4e78d443b53385eb7f99428.png"},{"id":105223590,"identity":"a163d4f6-f3f4-4e95-9885-9dec93a778de","added_by":"auto","created_at":"2026-03-23 16:08:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1348738,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8117555/v1/81b187d0-0d3c-4ab4-842a-1b5b72f6eb5d.pdf"},{"id":97271900,"identity":"beff28c5-d6db-40a8-98e4-07c23686ee7e","added_by":"auto","created_at":"2025-12-02 15:04:36","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":18420,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialLiveBirthsAfterLowInitialhCGBMCPregnancyChildbirth.docx","url":"https://assets-eu.researchsquare.com/files/rs-8117555/v1/1af6cd34f0f1690f90261e9a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Live Births After Low Initial β-hCG in IVF Cycles: A Retrospective Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eThe emotional, physical, and financial burden of in vitro fertilization (IVF) often leaves patients in a state of stress surrounding the outcome of their treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. When compared to unassisted pregnancies, patients who conceive through IVF exhibit higher levels of anxiety and depression symptoms [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Anxiety tends to increase with each stage, with the highest levels observed after embryo transfer to the pregnancy test [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Effective counselling is imperative for patient well-being, particularly for patients undergoing fertility treatments [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Providing information on the prognosis can prepare patients for adverse outcomes and allow them to make an informed decision about the pregnancy.\u003c/p\u003e\u003cp\u003eSerum beta-human chorionic gonadotropin (β-hCG) hormone is a well-supported biomarker used for pregnancy testing, monitoring, and prognosis. After a successful embryo transfer and implantation, the syncytial trophoblast of the growing placenta begins to secrete β-hCG, which can be detected in the patient\u0026rsquo;s serum to confirm the pregnancy. If positive, serial β-hCG levels will be evaluated for quantity and trend as these levels provide important information about the development of the pregnancy. It is widely acknowledged that higher β-hCG levels are correlated with positive pregnancy outcomes [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Clinicians are currently using β-hCG levels to counsel patients on the likelihood of a live birth, particularly when the initial level is high.\u003c/p\u003e\u003cp\u003eComparatively, numerous studies have described a β-hCG cut-off point below which the prognosis for live birth is poor [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The literature lacks well-defined statistics on the prevalence of live birth following a low initial serum β-hCG and how to interpret the trend of β-hCG rise in this context. This ambiguity presents a challenge in patient counselling and decision-making in IVF treatments. At Mount Sinai Fertility (MSF), patients with an initial β-hCG\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL are typically counselled that their pregnancy is unlikely to be viable and to monitor for signs and symptoms of pregnancy loss and ectopic pregnancy.\u003c/p\u003e\u003cp\u003eDue to the lack of data published in the literature, patients cannot be provided with a reliable prognosis for a healthy pregnancy when their initial level is low. Therefore, our objective was to determine the prevalence of live births after IVF with a low initial β-hCG and to identify β-hCG patterns associated with a very low likelihood of live birth. This can inform patient counselling and prevent unnecessary intervention in viable and wanted pregnancies. Unlike existing studies that focus on a single cycle type, we considered both fresh and frozen cycles, as well as cycles that employed preimplantation genetic testing for aneuploidy (PGT-A). We identified patient and cycle characteristics that increase the likelihood of a positive pregnancy outcome.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe conducted a single-centre retrospective cohort study of all pregnancies conceived following in vitro fertilization (IVF) between January 2019 and December 2022 at Mount Sinai Fertility, Toronto, Canada. Research ethics approval was granted by the Mount Sinai Hospital Research Ethics Board (23-0054-C).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003ePatients who achieved pregnancy, defined by a positive β-hCG (\u0026ge;\u0026thinsp;3 mIU/mL), after a frozen or fresh embryo transfer cycle were included. Both autologous and donor oocyte conceptions were included. If patients had more than one pregnancy within the timeframe, each pregnancy was assessed and recorded individually. Exclusion criteria encompassed patients who did not undergo embryo transfer and those with an undetectable β-hCG post-transfer. Demographic data were collected from the patient\u0026rsquo;s electronic medical record, including age at oocyte retrieval, body mass index (BMI), reason for IVF treatment, gravidity, parity, and duration of infertility in months. Cycle characteristics collected were fresh or frozen embryo, method of fertilization (conventional IVF vs. intracytoplasmic sperm injection (ICSI), endometrial preparation protocol, number of embryos transferred, use of preimplantation genetic testing for aneuploidy (PGT-A), and developmental stage of embryo transfer (cleavage stage or blastocyst day 5\u0026ndash;7). These variables were selected based on clinical relevance and existing literature demonstrating their association with live birth outcomes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Serum β-hCG levels were drawn at 14 days post-fertilization. A low initial serum β-hCG was defined as \u0026le;\u0026thinsp;50 mIU/mL, consistent with the lowest thresholds commonly reported in the literature [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Serum β-hCG was measured at our internal laboratory, with a small number of tests performed externally.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDefinitions of pregnancy outcomes\u003c/h3\u003e\n\u003cp\u003eReproductive outcomes included biochemical pregnancy loss: the spontaneous decrease in β-hCG before confirmation by ultrasound or histopathology; clinical pregnancy loss: ultrasound or histopathologic confirmation of a gestational sac; ectopic pregnancy: implantation outside of the uterus; resolved pregnancy of unknown location: resolved elevated β-hCG without visualization of the gestation inside the uterus; therapeutic abortion: termination of pregnancy; and ongoing clinical pregnancy: pregnancy at 10 weeks\u0026rsquo; gestation with ultrasound confirmation of fetal heartbeat. Birth data were sourced from the Better Outcomes Registry \u0026amp; Network (BORN) Ontario, with pregnancy outcomes categorized into live birth term delivery, live birth preterm delivery, late clinical pregnancy loss, and intrauterine fetal demise. Live births were defined as delivery of a fetus after 20 weeks\u0026rsquo; gestation with confirmation of life, with term gestation reflecting birth after 37 weeks. Late clinical pregnancy loss was defined as spontaneous abortion after 10 weeks of gestation. Intrauterine fetal demise was defined as the loss of a fetus after 20 weeks\u0026rsquo; gestation. Sonographic information was collected, including the number of gestational sacs, the number of embryos detected, and the number of fetal heartbeats. The primary outcome of the study was live birth.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003ePatient and cycle characteristics were analyzed using means with standard deviations or medians and interquartile ranges for continuous variables, and frequencies and percentages for categorical variables. Univariable and multivariable logistic mixed-effects regression models were created to determine the association between patient and cycle factors and live birth outcomes, with results reported as odds ratios (OR) with 95% confidence intervals and p-values (significance at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Receiver operating characteristic (ROC) curves were generated to evaluate the discriminatory performance of both the initial β-hCG levels and the trend of β-hCG levels for live birth outcomes. For each analysis, sensitivity, specificity, positive predictive value and negative predictive value were calculated, and cut-points were defined using the Youden index to optimize the balance of sensitivity and specificity, with an additional cut-point selected to maximize sensitivity. The area under the curve (AUC) with interquartile ranges was calculated to assess diagnostic accuracy, with an area of 1.00 indicating a perfect test.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003ePatient Characteristics\u003c/h2\u003e\u003cp\u003eThe median age at the time of egg retrieval was 34.0 [31.0, 37.0]. The median BMI was 24.5kg/m\u0026sup2; [21.6, 28.2]. Patients reported several reasons for seeking IVF treatment, the most common of which were male factor (28.7%), unexplained infertility (21.2%), and advanced maternal age (16.7%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). [Insert Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here]\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\u003eCharacteristics of study population from MSF who underwent IVF between January 2019 and December 2022\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCategories\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCohort\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2443\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003ePatient's age at time of egg retrieval, median years [IQR] \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.0 [31.0, 37.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, median kg/m\u0026sup2; [IQR] \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24.5 [21.6, 28.2]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOocyte source, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAutologous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2140 (87.6)\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\u003eDonor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e274 (11.2)\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\u003eReciprocal IVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29 (1.19)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObstetric history, median n [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGravidity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.00 [0.00, 2.00]\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\u003eParity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.00 [0.00, 1.00]\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\u003ePrior pregnancy losses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.00 [0.00, 1.00]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of infertility, median months [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19.0 [9.00, 32.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReasons for seeking treatment, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale factor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e702 (28.7)\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\u003eUnexplained infertility\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e608 (24.9)\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\u003eAdvanced female age\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e518 (21.2)\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\u003eDiminished ovarian reserve\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e408 (16.7)\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\u003eTubal factor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e255 (10.4)\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\u003ePolycystic ovary syndrome (PCOS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e238 (9.74)\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\u003eEndometriosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e194 (7.94)\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\u003eNo male partner\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e128 (5.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsemination method, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eConventional IVF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e806 (33.0)\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\u003eICSI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1631 (66.8)\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\u003eIVF and ICSI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (0.25)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmbryo transfer type, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrozen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1897 (77.7)\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\u003eFresh\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e546 (22.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndometrial preparation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOvulatory FET\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e367 (15.0)\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\u003eProgrammed FET\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1485 (60.7)\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\u003eModified ovulatory FET\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e45 (1.84)\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\u003eFresh embryo transfer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e546 (22.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePGT-A performed, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e624 (25.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePGT-A result of transferred embryo, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEuploid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e601 (96.3)\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\u003eMosaic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (2.08)\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\u003eNo DNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8 (1.28)\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\u003eInconclusive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (0.32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage of embryo transfer, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCleavage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e88 (3.60)\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\u003eBlastocyst day 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1678 (68.7)\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\u003eBlastocyst day 6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e642 (26.3)\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\u003eBlastocyst day 7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e21 (0.86)\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\u003eBlastocysts day 5 and 6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (0.53)\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\u003eBlastocysts day 6 and 7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.04)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmbryos transferred, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSingle embryo transfer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2185 (89.4)\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\u003eDouble embryo transfer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e257 (10.5)\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\u003eTriple embryo transfer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.04)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial serum β-hCG, median mIU/mL [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e130 [65.0, 216]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ea Missing age from 9 patients (0.37%)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eb Missing BMI from 129 patients (5.28%)\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\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eBMI, body mass index; FET, frozen embryo transfer; ICSI, intracytoplasmic sperm injection; IQR, interquartile range; IVF, in vitro fertilization; PGT-A, preimplantation genetic testing for aneuploidy.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCycle Parameters\u003c/h2\u003e\u003cp\u003eIn our cohort, the majority of patients (2140; 87.6%) used autologous oocytes for embryo transfer, while 274 patients used donor oocytes (11.2%) and 29 patients used reciprocal IVF oocytes (1.19%). 1897 (77.7%) patients underwent frozen embryo transfer, and 546 (22.4%) underwent fresh transfer. Among transferred embryos, 1678 (68.7%) were day 5 blastocysts, 642 (26.3%) day 6 blastocysts, 21 (0.86%) day 7 blastocysts, and 88 (3.60%) were at the cleavage stage. There were 624 (25.5%) embryos screened with PGT-A before transfer. The full results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePregnancy Outcomes\u003c/h3\u003e\n\u003cp\u003eThe median initial β-hCG level was 130 mIU/mL [65.0, 216]. Initial β-hCG was intended to be collected at 14 days post-fertilization; the vast majority of the patient population followed this standardized collection time.\u003c/p\u003e\u003cp\u003eOut of the 2443 embryo transfers, 1575 pregnancies (64.5%) were ongoing at or beyond 10 weeks\u0026rsquo; gestation (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The remaining pregnancies resulted in biochemical pregnancy loss (483, 19.8%), clinical pregnancy loss (321, 13.1%), resolved pregnancy of unknown location (41, 1.68%), or ectopic pregnancy (18, 0.74%). Among the 1575 ongoing pregnancies, 1179 (74.6%) resulted in a live term delivery (\u0026ge;\u0026thinsp;37 weeks\u0026rsquo; gestation), 133 (8.42%) in a live preterm delivery (\u0026lt;\u0026thinsp;37 weeks\u0026rsquo; gestation), and 27 (1.71%) in a live birth of unknown gestational age. There were 132 (5.40%) with unknown outcomes beyond 10 weeks\u0026rsquo; gestation, mainly due to incomplete delivery data in the BORN Ontario after discharge from the MSF clinic at 10 weeks or delivery outside Ontario, Canada. Pregnancy outcomes are reflected in 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\u003ePregnancy outcomes at 10 weeks and delivery for patients stratified by initial serum β-hCG levels\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCategories\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAll study pregnancies\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePregnancies with initial serum β-hCG levels\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePregnancies with initial serum β-hCG levels\u0026thinsp;\u0026gt;\u0026thinsp;50 mIU/mL\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePregnancies with initial serum β-hCG levels\u0026thinsp;\u0026gt;\u0026thinsp;50 mIU/mL and multiple gestations\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2443\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e491\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1952\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy outcome at 10 weeks\u0026rsquo; gestation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBiochemical pregnancy loss\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e483 (19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e320 (65.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e163 (8.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eClinical pregnancy loss\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e321 (13.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70 (14.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e251 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eEctopic pregnancy loss\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18 (0.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (2.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5 (0.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eOngoing pregnancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1512 (61.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76 (15.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1436 (73.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eResolved pregnancy of unknown location\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41 (1.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (2.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e29 (1.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eVanishing twin ongoing pregnancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (0.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10 (0.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eViable twin gestation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51 (2.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e51 (2.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eViable triplet gestation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (0.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2 (0.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\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\u003eUnknown outcomes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (0.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5 (0.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy outcome at delivery, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLive birth term delivery (\u0026gt;\u0026thinsp;37 weeks)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1179 (48.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50 (10.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1129 (57.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17 (32.1)\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\u003eLive birth preterm delivery (\u0026lt;\u0026thinsp;37 weeks)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e133 (5.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (1.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e125 (6.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e22 (41.5)\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\u003eLive birth unknown gestation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (1.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e27 (1.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (5.66)\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\u003eLate clinical pregnancy loss (\u0026gt;\u0026thinsp;10 weeks\u0026rsquo; gestation, \u0026lt; 20 weeks\u0026rsquo; gestation)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e64 (2.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (1.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e58 (2.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (3.77)\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\u003eIntrauterine fetal demise (\u0026gt;\u0026thinsp;20 weeks\u0026rsquo; gestation)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24 (0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (0.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21 (1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (3.77)\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\u003eTherapeutic abortion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 (0.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15 (0.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\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\u003eUnknown outcomes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e132 (5.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (1.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e124 (6.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (13.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePregnancy Outcomes by Initial β-hCG levels\u003c/h2\u003e\u003cp\u003eAmong patients with an initial β-hCG between 3\u0026ndash;50 mIU/mL (n\u0026thinsp;=\u0026thinsp;491), the most frequent outcome was biochemical pregnancy loss, affecting 65.2% (n\u0026thinsp;=\u0026thinsp;320) of the group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Clinical pregnancy losses occurred in 70 patients (14.3%), resolved pregnancy of unknown location in 12 patients (2.44%) and ectopic pregnancy in 13 patients (2.65%). Final pregnancy outcomes were available for 98% (n\u0026thinsp;=\u0026thinsp;483) of patients with a low initial β-hCG; of these, the prevalence of live birth was 12% with 58 patients delivering live infants. The prevalence of ectopic pregnancies was disproportionately represented in lower β-hCG ranges. Of the 18 total ectopic pregnancies, 13 (72%) had an initial β-hCG\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL, and 16 (89%) were \u0026lt;\u0026thinsp;100 mIU/mL. Additionally, 61% (11/18) of ectopic cases involved patients aged 35 years or older. Only one ectopic case involved a euploid embryo.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eLogistic Mixed-Effects Models Predicting Live Birth\u003c/h2\u003e\u003cp\u003eBoth univariable and multivariable logistic mixed-effect regression models were used to identify predictors of live birth. With each 10 unit (mIU/mL) greater initial serum β-hCG, there was a statistically significant increase in the odds of live birth by 3.5%, OR\u0026thinsp;=\u0026thinsp;1.04, 95% CI [1.03, 1.04], after adjusting for age, BMI, stage of transfer, number of embryos transferred and use of PGT-A. A positive β-hCG after transfer of a euploid embryo conferred more than twice the odds of live birth compared to untested embryos, OR\u0026thinsp;=\u0026thinsp;2.24, 95% CI [1.82, 2.76]. Slower growing blastocyst transfer (day 6 and day 7) significantly lowered odds of live birth compared to day 5 blastocysts, even after adjustment (Day 6: OR\u0026thinsp;=\u0026thinsp;0.70, 95% CI [0.57, 0.85]; Day 7: OR\u0026thinsp;=\u0026thinsp;0.26, 95% CI [0.09, 0.74]). Lastly, the number of embryos transferred was inversely correlated with live birth (OR\u0026thinsp;=\u0026thinsp;0.44, 95% CI [0.39, 0.51]). Age at oocyte retrieval, BMI and cleavage-stage transfers were not significant predictors in the multivariable models (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Results from logistic mixed-effects models are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariable and multivariable logistic mixed-effects models evaluating predictors of live birth\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" 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\u003cp\u003ePredictor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eMultivariable\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial serum β-hCG (per 10 units)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.03, 1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.03, 1.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at egg retrieval (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.97, 1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.98, 1.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.96, 0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.98, 1.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage: Blastocyst day 5 (Reference)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage: Blastocyst day 6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.63, 0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.57, 0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage: Blastocyst day 7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.09, 0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.09, 0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage: Cleavage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.41, 0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.69, 1.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of embryos transferred\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.28, 0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.39, 0.51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePGT-A (Yes)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.95, 2.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.82, 2.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eReceiver Operating Characteristic (ROC) Curve Analysis\u003c/h2\u003e\u003cp\u003eThe ROC curve analysis was conducted to evaluate the discriminatory performance of initial β-hCG for live birth outcomes. The area under the curve (AUC) was 0.726 (95% CI [0.705, 0.746]), indicating acceptable discrimination between live birth and no live birth. The optimal threshold that balances sensitivity and specificity using the Youden index was an initial β-hCG of 100.5 mIU/mL (sensitivity 0.79, specificity 0.57). A secondary logistic mixed-effects analysis using β-hCG above this threshold showed significantly increased odds of live birth, after adjusting for patient and cycle characteristics (OR\u0026thinsp;=\u0026thinsp;5.18, 95% CI [4.14, 6.47]) (Supplementary data). This corresponds to a 418% increase. To characterize β-hCG values below which live birth was uncommon, we performed ROC analysis prioritizing maximal sensitivity (1.00). This analysis indicated that more than 99% of live births occurred above an initial β-hCG of 22.5 mIU/mL with a NPV of 97.6%. The rate of change from initial β-hCG provided greater discriminatory value among patients with low initial β-hCG (AUC 0.876 [0.84, 0.91]) compared to those with an initial β-hCG\u0026thinsp;\u0026gt;\u0026thinsp;50 mIU/mL (AUC 0.584 [0.56, 0.61]). In the low initial β-hCG subgroup, the optimal threshold of 44% daily increase resulted in significantly stronger specificity (0.72) and negative predictive value (0.99), compared to the optimal threshold of 46% in the \u0026gt;\u0026thinsp;50 mIU/mL subgroup (specificity 0.25, negative predictive value 0.70). The ROC curves are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. [Insert Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here]\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eA clear understanding of the prognosis associated with a low initial β-hCG is essential for early pregnancy counselling. In this retrospective analysis, among the 491 patients with an initial β-hCG level\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL, the prevalence of live births was 12%, resulting in 50 term and eight preterm births. The lowest level that resulted in a live birth was 6 mIU/mL, measured 14 days post-fertilization, which tripled in 48 hours. Several studies have also documented live births from IVF despite very low initial β-hCG [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In one large retrospective cohort study, three cases of live births were reported with initial β-hCG levels of 5, 6, and 8 mIU/mL [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our results demonstrate that pregnancies with a low initial β-hCG have the potential to result in a live birth.\u003c/p\u003e\u003cp\u003eInterestingly, we found a higher proportion of ectopic pregnancies among the low β-hCG group compared to the high β-hCG group (2.65% vs 0.26%). However, none of these cases had significant risk factors for ectopic pregnancy (e.g. tubal disease, prior ectopic pregnancy). These findings underscore the importance of vigilant follow-up when early hormone levels are low.\u003c/p\u003e\u003cp\u003ePGT-A is widely recognized for its role in selecting viable embryos and reducing the risk of pregnancy loss [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Our study uniquely included PGT-A in the multivariable model for live birth. While the initial β-hCG remained a significant predictor, the transfer of a PGT-A-tested euploid embryo was independently associated with live birth after adjusting for early β-hCG levels. In our cohort, the use of a euploid embryo more than doubled the odds of live birth. Therefore, the advantage associated with PGT-A is not entirely captured by the initial hormone level. Similarly, our analysis revealed that day-5 blastocyst transfers were associated with increased odds of live birth compared with cleavage-stage or day-6 and day-7 blastocyst transfers, which is consistent with prior studies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Of the 58 live births with a low initial β-hCG, over half of them were blastocyst day-5 transfers and only three cycles were transferred at the cleavage stage. In addition to the timing of transfer, we found that the increase in the number of embryos transferred was associated with a decrease in the odds of a live birth. Our result is likely attributable to confounding by indication; patients with advanced reproductive age or a history of recurrent implantation failure are more likely to undergo multiple embryo transfers, although they are also at a poorer prognosis [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eYounger maternal age was associated with increased odds of live birth, although this association was not statistically significant. Patients with a low initial β-hCG were modestly older (34.40\u0026thinsp;\u0026plusmn;\u0026thinsp;4.64 vs. 33.79\u0026thinsp;\u0026plusmn;\u0026thinsp;4.60 years). In addition, advanced maternal age (\u0026ge;\u0026thinsp;40 years) was more prevalent among those with pregnancy loss at 10 weeks\u0026rsquo; gestation, in both low and high initial β-hCG groups. This is in agreement with the literature on the impact of advanced maternal age [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A lower BMI appeared predictive of a live birth; however, after adjusting for other cycle and patient characteristics, its statistical significance was lost. In line with previous studies [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], among pregnancies that resulted in live births, we found that the mean maternal BMI was higher in those with a low initial β-hCG (28.22\u0026thinsp;\u0026plusmn;\u0026thinsp;6.77 kg/m\u0026sup2;) compared with those with a high initial β-hCG (25.09\u0026thinsp;\u0026plusmn;\u0026thinsp;5.07 kg/m\u0026sup2;). In our study, patient characteristics were associated with live birth rates in the univariable analysis, but only cycle characteristics remained significant in the multivariable model.\u003c/p\u003e\u003cp\u003eAs expected, the initial serum β-hCG was predictive of a positive pregnancy outcome; for each 10-unit greater initial β-hCG, there was a statistically significant increase in live birth rates, while adjusting for patient and cycle characteristics. Our ROC curve identified 100.5 mIU/mL (AUC 0.726) as the optimal cut-point with the greatest sensitivity and specificity for predicting live birth. Among patients with an initial β-hCG above this value, 66.4% delivered. The reliability of a high initial β-hCG in predicting positive pregnancy outcomes has been well supported [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The 100.5 mIU/mL level is comparable to that in the literature, with a similar sensitivity (~\u0026thinsp;80%) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The utility of a single time-point threshold for predicting positive pregnancy outcomes is limited because a range of β-hCG collection days is reported in the literature.\u003c/p\u003e\u003cp\u003eOur study confirms live births can occur with β-hCG well below those thresholds. To better reflect the observed prevalence of live births after a low initial β-hCG, we explored a model that prioritized sensitivity. An initial β-hCG of 22.5 mIU/mL captured over 99% of patients who ultimately had a live birth. Although this value should not be interpreted as a clinical threshold, it provides valuable context for counselling patients with low initial β-hCG. Live birth was extremely uncommon below this level, underscoring the low likelihood of viability. There is a lot of ambiguity regarding the prognosis of these pregnancies, with some recommending discontinuing luteal phase support if the initial β-hCG\u0026thinsp;\u0026lt;\u0026thinsp;58.8 mIU/mL [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Our findings identify a β-hCG level with a wider catchment for live births to minimize the risk of incorrectly dismissing viable pregnancies.\u003c/p\u003e\u003cp\u003eThe trajectory of β-hCG rise also has prognostic relevance, beyond the absolute initial level. The doubling time of β-hCG is a well-established predictor of live birth [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Unique to previous studies, we performed an ROC subgroup analysis on two distinct ranges of β-hCG values. The rate of change from initial β-hCG was a stronger discriminator of live birth among patients with an initial serum β-hCG\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL (AUC 0.876 [0.84, 0.91]) than among those with an initial β-hCG\u0026thinsp;\u0026gt;\u0026thinsp;50 mIU/mL (AUC 0.584 [0.56, 0.61]). In the low initial β-hCG subgroup, 99% of patients who did not meet the optimal 44% daily increase of β-hCG did not deliver a live birth. In comparison to the β-hCG\u0026thinsp;\u0026gt;\u0026thinsp;50 mIU/mL subgroup, where only 70% of patients who did not meet the 46% threshold failed to deliver. There were no cases of live births after a decline in β-hCG. To our knowledge, this is the first study to demonstrate that the discriminatory performance of β-hCG rise is significantly greater in patients with initially low levels. Prior research has also highlighted the discriminatory value of β-hCG dynamics, with suggested thresholds of at least a 53% rise [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] or a 1.9-fold increase [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] in 48 hours. Our findings align with the POPI-Plus study, a predictive clinical model for live birth [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The authors found that a greater 48-hour rise was required to achieve the same live birth probability when the initial β-hCG level was lower, reflecting underlying physiologic variability.\u003c/p\u003e\u003cp\u003eOur study has several limitations. Although initial β-hCG was intended to be collected at a standardized time point, minor deviations in the collection day occurred. This may introduce differences in absolute values, which can limit its interpretation. Most β-hCG measurements were performed in our internal laboratory, but a minority were completed at external laboratories. This may introduce some inter-laboratory variation. We also did not collect any data on the morphologic quality of embryos and their correlation with live birth outcomes. Finally, as a retrospective single-centre study, our findings may be influenced by practice patterns at our institution and should be validated across diverse clinical settings. These findings are specific to pregnancies conceived via IVF/ICSI and may not be generalizable to spontaneous conceptions or other forms of assisted reproductive technology.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePatients with detectable but low β-hCG levels represent a vulnerable population. There is less known about their prognosis because, despite increased prevalence of adverse outcomes, there are cases of live births after remarkably low levels. This poses a challenge to clinicians when counselling patients in this group. Patients often hold unrealistic expectations when starting IVF [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Managing expectations with objective information has been shown to reduce feelings of distress and anxiety, and aid in informed decision-making for the current cycle and subsequent cycles [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our study demonstrates a 12% prevalence of live birth rates in this group, providing valuable information for setting patient expectations. By identifying 22.5 mIU/mL as a level that captured nearly all viable pregnancies, we were able to distinguish two subgroups of patients with a low initial β-hCG. This distinction supports more individualized prognostic counselling, as outcomes differ significantly between these groups. Notably, the use of a euploid embryo should inform counselling, as we saw the advantage of PGT-A is not entirely captured by the initial β-hCG level. Finally, we are able to demonstrate the unique impact of the rate of β-hCG rise on positive outcomes in this population. Our focus on live birth among patients with an initially low β-hCG was to increase transparency and address patients\u0026rsquo; calls for greater clarity in this unfamiliar process [\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In conclusion, our study contributes to growing evidence that a single low β-hCG value should be interpreted with careful consideration. Future directions should aim to validate our results in a multi-centre study.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"602\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMeaning\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eArea under the curve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026beta;-hCG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003ebeta-human chorionic gonadotropin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eBody mass index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eBORN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eBetter Outcomes Registry \u0026amp; Network\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eIntracytoplasmic sperm injection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eIn vitro fertilization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMSF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eMount Sinai Fertility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eOdds ratios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003ePGT-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003ePreimplantation genetic testing for aneuploidy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eROC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 351px;\"\u003e\n \u003cp\u003eReceiver operating characteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the Mount Sinai Hospital Research Ethics Board (IRB #23-0054-C), which granted a waiver of informed consent due to the use of de-identified clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data supporting the findings of this study are included in this article and its supplementary file. The patient-level dataset cannot be shared publicly due to institutional and ethical restrictions. Fully de-identified data may be made available from the corresponding author upon reasonable request and with approval from the Mount Sinai Hospital Research Ethics Board.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.D and V.B conceptualized and designed the study. S.D, K.M, and D.A completed data extraction and preliminary analysis. Q.L and E.H conducted statistical analysis. S.D, K.M, and D.A wrote the manuscript under the guidance of V.B. All authors read the final draft and approved its submission for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors' information\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSierra DiMarco is a medical student at Queen’s University with a Masters of Biomedical Science from the University of Guelph. With training in assisted reproductive biotechnologies, her clinical interest is reproductive endocrinology and early pregnancy outcomes. Her current research focuses on prognosis after IVF and enhancing patient-centred counselling.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eParaskevi L, Antigoni S, Kleanthi G. 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Symptomatic Patients With an Early Viable Intrauterine Pregnancy: hCG Curves Redefined. Obstet Gynecol. 2004;104:50. doi:10.1097/01.AOG.0000128174.48843.12.\u003c/li\u003e\n\u003cli\u003eChung K, Sammel MD, Coutifaris C, Chalian R, Lin K, Castelbaum AJ, et al. Defining the rise of serum HCG in viable pregnancies achieved through use of IVF. Hum Reprod. 2006;21:823\u0026ndash;8. doi:10.1093/humrep/dei389.\u003c/li\u003e\n\u003cli\u003eMcLernon DJ, Steyerberg EW, Te Velde ER, Lee AJ, Bhattacharya S. Predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation: population based study of linked cycle data from 113 873 women. BMJ. 2016;:i5735. doi:10.1136/bmj.i5735.\u003c/li\u003e\n\u003cli\u003eShi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018;378:126\u0026ndash;36. doi:10.1056/NEJMoa1705334.\u003c/li\u003e\n\u003cli\u003eBjercke S, Tanbo T, Dale PO, M\u0026oslash;rkrid L, \u0026Aring;byholm T. Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization. Hum Reprod. 1999;14:1642\u0026ndash;6. doi:10.1093/humrep/14.6.1642.\u003c/li\u003e\n\u003cli\u003eOron G, Esh-Broder E, Son W-Y, Holzer H, Tulandi T. Predictive value of maternal serum human chorionic gonadotropin levels in pregnancies achieved by in vitro fertilization with single cleavage and single blastocyst embryo transfers. Fertil Steril. 2015;103:1526-1531.e1-2. doi:10.1016/j.fertnstert.2015.02.028.\u003c/li\u003e\n\u003cli\u003eWu Y, Liu H. Possibility of live birth in patients with low serum \u0026beta;-hCG 14\u0026thinsp;days after blastocyst transfer. J Ovarian Res. 2020;13:132. doi:10.1186/s13048-020-00732-6.\u003c/li\u003e\n\u003cli\u003eBurks HR, Baker M, Quaas AM, Bendikson KA, Chung K, Paulson RJ. The dilemma of counseling patients about poor prognosis: live birth after IVF with autologous oocytes in a 43-year-old woman with FSH levels above 30 mIU/mL. J Assist Reprod Genet. 2017;34:1185\u0026ndash;8. doi:10.1007/s10815-017-0986-3.\u003c/li\u003e\n\u003cli\u003eHughes LM, Schuler A, Sharmuk M, Schauer JM, Pavone ME, Bernardi LA. Early \u0026beta;-hCG levels predict live birth after single embryo transfer. J Assist Reprod Genet. 2022;39:2355\u0026ndash;64. doi:10.1007/s10815-022-02606-w.\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. Hum Reprod. 2021;36:2339\u0026ndash;44. doi:10.1093/humrep/deab117.\u003c/li\u003e\n\u003cli\u003eKathiresan ASQ, Cruz-Almeida Y, Barrionuevo MJ, Maxson WS, Hoffman DI, Weitzman VN, et al. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fertil Steril. 2011;96:1362\u0026ndash;6. doi:10.1016/j.fertnstert.2011.09.042.\u003c/li\u003e\n\u003cli\u003eESHRE Guideline Group on the Number of Embryos to Transfer, Alteri A, Arroyo G, Baccino G, Craciunas L, De Geyter C, et al. ESHRE guideline: number of embryos to transfer during IVF/ICSI\u0026dagger;. Hum Reprod. 2024;39:647\u0026ndash;57. doi:10.1093/humrep/deae010.\u003c/li\u003e\n\u003cli\u003eLean SC, Derricott H, Jones RL, Heazell AEP. Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis. PLoS One. 2017;12:e0186287. doi:10.1371/journal.pone.0186287.\u003c/li\u003e\n\u003cli\u003eBrady PC, Farland LV, Ginsburg ES. Serum Human Chorionic Gonadotropin Among Women With and Without Obesity After Single Embryo Transfers. J Clin Endocrinol Metab. 2018;103:4209\u0026ndash;15. doi:10.1210/jc.2018-01057.\u003c/li\u003e\n\u003cli\u003eEskild A, Fedorcsak P, M\u0026oslash;rkrid L, Tanbo TG. Maternal body mass index and serum concentrations of human chorionic gonadotropin in very early pregnancy. Fertil Steril. 2012;98:905\u0026ndash;10. doi:10.1016/j.fertnstert.2012.06.011.\u003c/li\u003e\n\u003cli\u003eMourad A, Antaki R, Rowen M, L\u0026eacute;vesque \u0026Eacute;, Lapens\u0026eacute;e L. The POPI-Plus tool: prediction model of outcome of pregnancy in in vitro fertilization from a large retrospective cohort. Fertil Steril. 2024;121:489\u0026ndash;96. doi:10.1016/j.fertnstert.2023.11.035.\u003c/li\u003e\n\u003cli\u003eCopp T, Kvesic D, Lieberman D, Bateson D, McCaffery KJ. \u0026lsquo;Your hopes can run away with your realistic expectations\u0026rsquo;: a qualitative study of women and men\u0026rsquo;s decision-making when undergoing multiple cycles of IVF. Hum Reprod Open. 2020;2020:hoaa059. doi:10.1093/hropen/hoaa059.\u003c/li\u003e\n\u003cli\u003eFauser BCJM, Boivin J, Barri PN, Tarlatzis BC, Schmidt L, Levy-Toledano R. Beliefs, attitudes and funding of assisted reproductive technology: Public perception of over 6,000 respondents from 6 European countries. PLoS One. 2019;14:e0211150. doi:10.1371/journal.pone.0211150.\u003c/li\u003e\n\u003cli\u003eWyndham N, Marin Figueira PG, Patrizio P. A persistent misperception: assisted reproductive technology can reverse the \u0026ldquo;aged biological clock.\u0026rdquo; Fertil Steril. 2012;97:1044\u0026ndash;7. doi:10.1016/j.fertnstert.2012.02.015.\u003c/li\u003e\n\u003cli\u003eGonda KJ, Domar AD, Gleicher N, Marrs RP. Insights from clinical experience in treating IVF poor responders. Reprod Biomed Online. 2018;36:12\u0026ndash;9. doi:10.1016/j.rbmo.2017.09.016.\u003c/li\u003e\n\u003cli\u003eDancet EAF, Nelen WLDM, Sermeus W, De Leeuw L, Kremer JAM, D\u0026rsquo;Hooghe TM. The patients\u0026rsquo; perspective on fertility care: a systematic review. Hum Reprod Update. 2010;16:467\u0026ndash;87. doI:10.1093/humupd/dmq004.\u003c/li\u003e\n\u003cli\u003eHarrison C, Gameiro S, Boivin J. Patient willingness, preferences and decision-making about planning for three complete cycles of IVF/ICSI treatment. Hum Reprod. 2021;36:1339\u0026ndash;52. doi:10.1093/humrep/deab040.\u003c/li\u003e\n\u003cli\u003eSousa-Leite M, Costa R, Figueiredo B, Gameiro S. Discussing the possibility of fertility treatment being unsuccessful as part of routine care offered at clinics: patients\u0026rsquo; experiences, willingness, and preferences. Hum Reprod. 2023;38:1332\u0026ndash;44. doi:10.1093/humrep/dead096.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"IVF, β-hCG, live birth, early pregnancy, embryo transfer, ICSI, PGT-A, pregnancy prognosis","lastPublishedDoi":"10.21203/rs.3.rs-8117555/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8117555/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSerum beta-human chorionic gonadotropin (β-hCG) hormone is a well-established biomarker used for pregnancy monitoring and prognosis in in vitro fertilization (IVF) cycles. After embryo transfer, a high serum β-hCG level with a prompt doubling time is typically reassuring, while a low initial β-hCG often leads to counselling around likely impending pregnancy loss and/or ectopic pregnancy. However, the number of patients with low β-hCG who ultimately deliver a live birth is unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis is a single-centre retrospective cohort study of IVF pregnancies between January 2019 and December 2022. Serum β-hCG was drawn 14 days post-fertilization. We considered an initial β-hCG\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL as low. A logistic mixed-effects regression model assessed the odds of live birth for every 10 mIU/mL increase in β-hCG, adjusting for patient and cycle characteristics (age, body mass index, embryo stage, number of embryos transferred, and preimplantation genetic testing for aneuploidy). Receiver operating characteristic curves were plotted to determine optimal cut-points.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 2443 pregnancies, the prevalence of live birth was 12% for those with an initial β-hCG\u0026thinsp;\u0026le;\u0026thinsp;50 mIU/mL. For each 10 mIU/mL difference in initial β-hCG, the odds of live birth increased significantly (aOR\u0026thinsp;=\u0026thinsp;1.035, 95% CI: 1.027, 1.042). Receiver operating characteristic curve analysis showed that an initial β-hCG greater than 22.5 mIU/mL identified over 99% of patients who ultimately had a live birth (sensitivity 1, specificity 0.21, AUC 0.726). The rate of change from initial β-hCG demonstrated stronger discriminatory performance for live birth among patients with low initial β-hCG (AUC 0.876 [0.84, 0.91]) than among those with an initial β-hCG\u0026thinsp;\u0026gt;\u0026thinsp;50 mIU/mL (AUC 0.584 [0.56, 0.61]).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eWhile IVF pregnancies with a low initial β-hCG can result in live birth, the likelihood is low. The rate of β-hCG rise emerged as a stronger discriminator of pregnancy outcomes when the initial β-hCG is low. Live birth was extremely rare when the initial β-hCG was below 22.5 mIU/mL. These findings offer prognostic data to guide counselling and refine expectations after IVF.\u003c/p\u003e","manuscriptTitle":"Live Births After Low Initial β-hCG in IVF Cycles: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 15:04:32","doi":"10.21203/rs.3.rs-8117555/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-20T08:42:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-17T13:34:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"178962109244627536395354466761123164667","date":"2026-02-16T13:58:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-20T17:09:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"10046120317418831341955690102178566123","date":"2026-01-14T16:24:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141750974421479127609332789913872149207","date":"2026-01-14T10:18:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-01T05:50:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-17T10:47:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-15T10:27:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-15T10:25:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-11-14T18:08:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1777c10f-f50d-4e47-a597-8d0e96c71430","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:05:23+00:00","versionOfRecord":{"articleIdentity":"rs-8117555","link":"https://doi.org/10.1186/s12884-026-08957-x","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2026-03-18 15:58:50","publishedOnDateReadable":"March 18th, 2026"},"versionCreatedAt":"2025-12-02 15:04:32","video":"","vorDoi":"10.1186/s12884-026-08957-x","vorDoiUrl":"https://doi.org/10.1186/s12884-026-08957-x","workflowStages":[]},"version":"v1","identity":"rs-8117555","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8117555","identity":"rs-8117555","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}