Comparison of Cumulative Live Birth Rates and Cost-Effectiveness Between GnRH Antagonist and Progestin-Primed Ovarian Stimulation Protocols Running title: Cost-effectiveness of GnRH-ant vs PPOS

Comparison of Cumulative Live Birth Rates and Cost-Effectiveness Between GnRH Antagonist and Progestin-Primed Ovarian Stimulation Protocols Running title: Cost-effectiveness of GnRH-ant vs PPOS | 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 Article Comparison of Cumulative Live Birth Rates and Cost-Effectiveness Between GnRH Antagonist and Progestin-Primed Ovarian Stimulation Protocols Running title: Cost-effectiveness of GnRH-ant vs PPOS Jui-Chun Chang, Yu-Chiao Yi, Hwa-Fen Guu, Ya-Fang Chen, Li-Yu Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6803353/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: This study compared the cumulative live birth rates (CLBRs) and cost-effectiveness of the GnRH antagonist (GnRH-ant) versus progestin-primed ovarian stimulation (PPOS) protocols in controlled ovarian stimulation (COS). Methods: In this retrospective study, women who underwent COS with GnRH-ant or PPOS at Taichung Veterans General Hospital, from 2018 through 2022, were analyzed. After applying exclusion criteria, eligible participants were matched in a 3:1 ratio using propensity score matching based on age and anti-Müllerian hormone levels. Clinical outcomes and cost-effectiveness were evaluated, with incremental cost-effectiveness ratio (ICER) and probabilistic sensitivity analysis (PSA) conducted based on various willingness-to-pay (WTP) thresholds. Results: A total of 225 patients who underwent COS with GnRH-ant and 85 patients with PPOS were included. GnRH-ant required significantly lower gonadotropin doses, a shorter stimulation duration, and yielded a higher MII oocyte rate. Pregnancy and live birth rates after the first embryo transfer were similar between the two protocols, while the GnRH-ant group had a numerically higher CLBR (56.08% vs 54.12%) and a significantly shorter time from stimulation to live birth (351.28 ± 138.59 vs. 394.42 ± 105.90 days, p < 0.001) per aspirated cycle compared to PPOS. Medical costs by procedure and in total were comparable, with an ICER of $2,067.14 per additional live birth for GnRH-ant. PSA indicated a 40% probability of cost-effectiveness at a $2,000 WTP threshold, with the probability increasing to 58.0% at $10,000 and 61.3% at $30,000. Conclusion: Both protocols yielded similar pregnancy and live birth outcomes, with GnRH-ant being a cost-effective option under more lenient WTP settings. Moreover, GnRH-ant was associated with a shorter time from stimulation to live birth, potentially benefiting women who seek to conceive sooner. Health sciences/Endocrinology Health sciences/Health care Health sciences/Medical research Progestin-primed ovarian stimulation gonadotrophin-releasing hormone antagonist cost-effectiveness cumulative live birth rate controlled ovarian stimulation assisted reproductive technology Figures Figure 1 INTRODUCTION Infertility, defined as the inability to conceive after more than one year of regular unprotected intercourse, affects approximately one in six individuals worldwide. 1 The estimated global lifetime prevalence of infertility is 17.5%, with higher regional prevalence reported in the Western Pacific (23.2%) and the Americas (20.0%). 1 Reflecting these trends, the European Society of Human Reproduction and Embryology reported that in 2021, the total fertility rate in the EU was 1.53 births per woman, with nearly 3% of all births resulting from assisted reproductive technologies (ART). 2 Approximately one-third of all ART cycles worldwide were initiated in Europe, yielding a cumulative live birth rate (CLBR) of 31.4% per aspiration. 3 – 5 While Japan, China, and the US were among the most active countries in ART utilization, Taiwan demonstrated relatively high ART accessibility, performing an estimated 2,104 cycles per million population. 3 This underscores the significance of the country’s ART experience in the Asia-Pacific region and globally. Controlled ovarian stimulation (COS) is a critical component of ART and fertility preservation treatments. COS typically involves follicular development stimulation, pituitary suppression, which prevents premature luteinizing hormone (LH) surges and enables controlled oocyte retrieval. This is followed by oocyte maturation triggering. 6 , 7 Gonadotropin-releasing hormone antagonists (GnRH-ant) are favored over gonadotropin-releasing hormone agonists for COS by guidelines and expert consensus due to similar live birth rates but a lower risk of ovarian hyperstimulation syndrome (OHSS). 6 – 8 In contrast to GnRH analogues, the progestin-primed ovarian stimulation (PPOS) protocol has gained attention over the past decade as an alternative for preventing premature LH surges. 9 , 10 However, due to the limited availability of randomized controlled trials directly comparing GnRH analogues and PPOS, evidence-based analyses regarding their relative clinical efficacy remain inconclusive. 11 Mechanistically, progestin exposure during the follicular phase induces premature endometrial advancement and asynchrony, precluding fresh embryo transfer (ET) within the same COS cycle. 12 – 14 There is also ongoing debate regarding the effects of COS protocols on oocyte quality and retrieval timing, 13 , 14 both of which may impact pregnancy and live birth rates. Consequently, clinical guidelines recommend limiting PPOS to cycles with planned freeze-all strategy, 6 favoring GnRH analogues when fresh ET is intended. Despite growing interest, cost-effectiveness studies comparing GnRH-ant and PPOS remain scarce. Existing analyses often vary in clinical efficacy endpoints, such as live birth rates and oocyte yield, or relying on simulation-based models. 15 – 20 In this study, we aim to compare cumulative live birth rates (CLBRs) and cost-effectiveness of GnRH-ant versus PPOS using real world and as-it-occurred data. The cost-effectiveness of two protocols was evaluated through incremental cost-effectiveness ratio (ICER) analysis and willingness-to-pay (WTP) thresholds for achieving a live birth. METHODS Study design and study population This retrospective study included women who underwent COS using either the GnRH-ant or PPOS protocol, followed by fresh ET and/or frozen embryo transfer (FET) at Taichung Veterans General Hospital, Taiwan, between 2018 and 2022. Exclusion criteria were: i) use of preimplantation genetic diagnosis and/or screening and, ii) failure to produce usable embryos after COS. Eligible participants were matched in a 3:1 ratio propensity score (GnRH-ant: PPOS) based on age and anti-Müllerian hormone (AMH) levels. The study protocol was reviewed and approved by the Institutional Review Board of Taichung Veterans General Hospital (IRB: CE24607A), and the requirement for informed consent was waived by the Institutional Review Board of Taichung Veterans General Hospital due to the retrospective nature of the study. This study was performed in adherence with the principles of the Declaration of Helsinki. COS protocol Ovarian stimulation began on menstrual cycle day 2 or 3 with the administration of 150–300 IU/day of recombinant human follicle-stimulating hormone (r-hFSH; Gonal-F) plus human menopausal gonadotropin (hMG; Menopur, 150–300 IU/day, providing both FSH and LH activity) or r-hFSH (150–300 IU/day) plus recombinant human luteinizing hormone (r-hLH; 75–150 IU/day) (Pergoveris, Merck-Serono, Germany). Dosage was adjusted based on patient response and physician discretion. For the GnRH-ant protocol, pituitary suppression was achieved with GnRH-ant (Cetrotide, 0.25 mg/day) in a flexible protocol, initiated when the dominant follicle reached 12–14 mm in diameter and continued until the trigger day. For the PPOS protocol, progestin (Provera, 5 mg twice daily) was administered from the start of stimulation until the trigger day. Ovulation was triggered when ≥ 3 dominant follicles reached an average diameter of > 17 mm using recombinant human chorionic gonadotropin (hCG) (Ovidrel, 250 µg) and/or GnRH agonist (Decapeptyl, 0.2 mg). Dual triggering has been a routine practice at the study site since 2014, except for high-risk OHSS patients, for whom GnRH agonist was used, and subsequent fresh ET was canceled. Oocyte retrieval occurred 35–37 hours post-trigger. Fertilization, ET, and clinical outcomes Oocytes were fertilized via in vitro fertilization or intracytoplasmic sperm injection 4–6 hours after retrieval. In fresh cycles, day 2 or day 3 embryos or day 5 blastocysts were transferred, while surplus embryos or blastocysts were vitrified. Each ET involved 1–4 fresh or frozen embryos, depending on the patient’s conditions. Luteal support for fresh ET, endometrial preparations for FET, and embryo thawing were performed as previously prescribed. 21 , 22 A complete ART cycle included one fresh ET and/or up to 4 FET. Pregnancy was confirmed by a positive β-hCG serum level tested 9–12 days after ET. Live birth was defined as the delivery of a live infant after a minimum of 24 gestational weeks. CLBR was defined as the first live birth achieved from one aspirated cycle, including all ETs until all embryos were used. Data collection and cost-effective analysis Demographic, laboratory, clinical, and cost-related data were retrieved from hospital records. The medical costs associated with ART — including COS, hormone and ultrasound monitoring, oocyte retrieval, fresh ET, FET, embryo cryopreservation, miscarriage, and OHSS — were analyzed. Childbirth costs were excluded, as not all women delivered their infants at the study site. Cost-effectiveness was assessed by calculating ICER, comparing the additional costs of the GnRH-ant protocol to PPOS in relation to the difference in CLBR. Incremental cost represents the difference in expenses per patient when choosing GnRH-ant over PPOS, while incremental effectiveness reflects the percentage increase in CLBR with GnRH-ant. Probabilistic sensitivity analysis (PSA) was performed using Monte Carlo simulation with 50,000 bootstrap iterations using the R package (v4.4.1). A cost-effectiveness plane was used, and a cost-effectiveness acceptability curve (CEAC) was generated to illustrate the probability of the GnRH-ant protocol being cost-effective across various WTP thresholds. Statistical analysis Statistical analyses were performed on an intention-to-treat basis. Continuous variables were presented as means ± standard deviations and analyzed using the Mann-Whitney U test or Wilcoxon rank-sum test. Categorical variables were expressed as counts and percentages, analyzed using the Chi-square test. A p-value < 0.05 was considered statistically significant. RESULTS Patient demographics After applying eligibility criteria and propensity matching, a total of 225 women who underwent COS with the GnRH antagonist protocol and 85 with PPOS were included in this retrospective study. The two groups had comparable baseline demographics and clinical characteristics, including age (36.49 ± 3.61 vs 36.49 ± 3.62 years), body mass index (22.78 ± 3.67 vs 23.04 ± 3.88 kg/m 2 ), duration of infertility (3.38 ± 2.52 vs 3.66 ± 2.72 years), and infertility type and cause (all p > 0.05, Table 1 ). Basal levels of AMH, FSH, and fertilization methods were also similar between patients who received GnRH-ant and PPOS. Table 1 . Baseline clinical characteristics of patients using GnRH antagonist and PPOS after propensity score matching. Variables GnRH antagonist (n=255) PPOS (n=85) P value Age 36.49 ± 3.61 36.49 ± 3.62 1.000 AMH (ng/ml) 2.28 ± 1.57 2.29 ± 1.59 0.943 BMI (kg/m 2 ) 22.78 ± 3.67 23.04 ± 3.88 0.634 Duration of Infertility (years) 3.38 ± 2.52 3.66 ± 2.72 0.452 Infertility 0.445 Primary 102 (40.0%) 38 (44.7%) Secondary 153 (60.0%) 47 (55.3%) Basal FSH (IU/L) 7.02 ± 2.92 6.33 ± 3.15 0.061 Cause of infertility 0.052 Tubal 47.0 (18.5%) 20.0 (23.5%) Male factor 24.0 (9.4%) 3.0 (3.5%) Anovulatory or diminished ovarian reserve 70.0 (27.6%) 15.0 (17.6%) Unexplained 23.0 (9.1%) 5.0 (5.9%) Endometriosis/adenomyosis 31.0 (12.2%) 20.0 (23.5%) Mixed factors 11.0 (4.3%) 4.0 (4.7%) Others 48.0 (18.9%) 18.0 (21.2%) Fertilization method 0.324 IVF 185.0 (72.5%) 57.0 (67.1%) ICSI 50.0 (19.6%) 23.0 (27.1%) Both 20.0 (7.8%) 5.0 (5.9%) Abbreviations: AMH: anti-Mullerian hormone; BMI: body mass index; FSH: follicle-stimulating hormone; GnRH: gonadotropin -releasing hormone; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; PPOS: progestin-primed ovarian stimulation. The analysis cohort was matched at 3 vs 1 (GnRH antagonist vs PPOS) for baseline age and AMH. Continuous data are reported as mean ± standard deviation, and the between-group difference was evaluated using Mann-Whitney U test. Categorical data are expressed as counts (percentages), and the between-group difference was examined using Chi-square test or Fisher’s exact test. Ovarian response and clinical efficacy outcomes Differences in ovarian response to COS are summarized in Table 2 . Compared to PPOS, the GnRH-ant protocol had significantly lower total FSH (3310.53 ± 1118.14 vs 3612.81± 1311.00 IU, p = 0.033) and LH dosage (1147.94 ± 680.59 vs 1413.09 ± 705.52 IU, p < 0.001), shorter stimulation duration (10.04 ± 1.54 vs 10.56 ± 1.71 days, p = 0.015), greater endometrial thickness on trigger day (11.55 ± 2.66 vs 8.85 ± 2.57 mm, p < 0.001), and higher oocyte maturation rate (0.78 ± 0.19 vs 0.69 ± 0.19, p < 0.001). Overall, OHSS incidence was low without statistically significant intergroup difference, with one moderate to severe case occurring in the PPOS group and none with GnRH-ant. The number of follicles ≥ 18mm and fertility hormones on trigger day, number of fertilized oocytes, oocyte fertilization rate, number of good-quality embryos on day 3, good-quality embryo rate on day 3, number of total blastocysts, blastocyst formation rate, number of good blastocysts (>3BB), good blastocyst rate, and number of embryos transferred did not differ significantly between the groups. Compared to PPOS, despite a lower incidence of day 5 blastocysts selected for the first ET in the GnRH-ant group (55.7% vs 84.7%, p 0.05). The weeks of delivery, preterm delivery ( 0.05). Table 2. Ovarian and embryo transfer outcomes between GnRH antagonist and PPOS protocols after propensity score matching. Variables GnRH antagonist (n=255) PPOS (n=85) p value Dosage of FSH (IU) 3310.53 ± 1118.14 3612.81 ± 1311.00 0.033 Dosage of LH (IU) 1147.94 ± 680.59 1413.09 ± 705.52 <0.001 Days of stimulation 10.04 ± 1.54 10.56 ± 1.71 0.015 On the trigger day Follicle size ≥ 18mm 1.92 ± 1.58 2.09 ± 1.73 0.564 Endometrial thickness (mm) 11.55 ± 2.66 8.85 ± 2.57 <0.001 Estradiol (pg/mL) 2614.28 ± 1756.05 2814.87 ± 2259.27 0.959 LH (IU/L) 1.69 ± 1.69) 1.66 ± 1.67 0.579 Progesterone (ng/mL) 0.89 ± 0.64) 0.88 ± 0.51 0.876 Number of retrieved oocytes 11.44 ± 7.80 13.14 ± 10.02 0.299 Oocyte retrieval rate 0.92 ± 0.30 0.98 ± 0.30 0.304 Number of mature oocyte 8.71 ± 5.90 8.66 ± 6.25 0.792 Maturation rate 0.78 ± 0.19 0.69 ± 0.19 <0.001 OHSS 0.250 # No or mild 255 (100%) 84 (98.8%) Moderate or severe 0 (0.0%) 1 (1.2%) Number of fertilized oocytes 7.99 ± 5.86 9.05 ± 7.09 0.331 Oocyte fertilization rate 0.73 ± 0.22 0.71 ± 0.19 0.300 Good-quality embryos on day 3 † 3.07 ± 2.47 3.28 ± 3.21 0.628 Good quality embryo rate on day 3 0.35 ± 0.22 0.32 ± 0.23 0.099 Number of total blastocyst 5.21 ± 4.28 5.01 ± 5.27 0.183 Blastocyst formation rate 0.57 ± 0.22 0.58 ± 0.22 0.861 Number of good blastocyst § 3.56 ± 3.48 3.49 ± 4.32 0.315 Good blastocyst rate 0.66 ± 0.32 0.66 ± 0.35 0.804 Number of embryos transferred 0.264 # 1 99 (38.8%) 25 (29.4%) 2 125 (49.0%) 52 (61.2%) 3 23 (9.0%) 7 (8.2%) 4 8 (3.1%) 1 (1.2%) Day of embryo at 1 st embryo transfer‡ <0.001 Day 2 36 (14.1%) 7 (8.2%) Day 3 77 (30.2%) 6 (7.1%) Day 5 142 (55.7%) 72 (84.7%) Pregnancy rate of 1 st embryo transfer 124 (48.6%) 49 (57.6%) 0.150 Live birth rate of 1 st embryo transfer 101 (39.6%) 38 (44.7%) 0.408 Weeks of delivery 37.31 ± 2.76 36.84 ± 3.17 0.547 Preterm (<37 weeks) 35 (25.0%) 12 (26.7%) 0.823 Birth weight 2861.68 ± 578.38 2718.89 ± 760.55 0.387 †Good-quality embryos = Grade 1 and Grade 2 ‡Including fresh and frozen embryo transfer. §Good blastocyst on day 5 = 3AB, 3BA, and 4 to 6. Abbreviations: FSH: follicle-stimulating hormone; GnRH: gonadotropin-releasing hormone; LH: luteinizing hormone; OHSS: ovarian hyperstimulation syndrome; PPOS: progestin-primed ovarian stimulation. Continuous data are reported as mean ± standard deviation, and the between-group difference was evaluated using Mann-Whitney U test. Categorical data are expressed as counts (percentages), and the between-group difference was examined using Chi-square test or # Fisher’s exact test. As shown in Table 3 , the time from ovarian stimulation to LB was significantly shorter in the GnRH-ant group compared to PPOS (351.28 ± 138.59 vs 394.42 ± 105.90 days, p <0.001). CLBR tended to be higher (56.08% vs 54.12%) and time from ET to LB shorter (248.60 ± 17.06 vs 260.87 ± 77.44 days) for the GnRH-ant group compared to PPOS, though the difference was not statistically significant. Table 3. Comparison of CLBRs and time to LB between the GnRH antagonist and PPOS groups. Variables GnRH antagonist (n=255) PPOS (n=85) p value CLBRs 143/255 (56.08%) 46/85 (54.12%) 0.850 Time from OS to LB (day) 351.28 ± 138.59 394.42 ± 105.90 <0.001 Time from ET to LB (day) 248.60 ± 17.06 260.87 ± 77.44 0.718 Abbreviations: CLBR: cumulative live birth rate; ET: embryo transfer; GnRH: gonadotropin hormone-releasing hormone; LB: live birth; OS: ovarian stimulation; PPOS: progestin-primed ovarian stimulation. Categorical data are expressed as percentages, and the between-group difference was examined using Chi square test. Continuous data are reported as mean ± SD, and the between-group difference was evaluated using Mann-Whitney U test. Cost-effectiveness and sensitivity analysis All medical costs, by procedure or in total, were comparable between the GnRH-ant and PPOS protocols, with the total cost per patient similar between the two protocols ($5125.57 ± 1018.15 vs $5085.04 ± 844.78, p>0.05) ( Table 4 ). Costs for fresh ET and 4 th FET were incurred only in the GnRH-ant group, while OHSS-related costs were exclusive to the PPOS group. Table 4. Mean medical costs associated with the GnRH antagonist and PPOS protocols. Type of cost (USD) GnRH antagonist (n=255) PPOS (n=85) p value COS 1991.88 ± 582.02 1867.31 ± 685.25 0.258 Hormonal test and sonography 136.51 ± 28.01 138.08 ± 24.66 0.481 OPU 1581.81 ± 202.47 1608.22 ± 214.51 0.085 Fresh ET 598.21 ± 233.36 N/A 1 st FET 942.56 ± 326.46 842.71 ± 236.84 0.199 2 nd FET 857.45 ± 241.39 755.51 ± 99.69 0.224 3 rd FET 942.10 ± 318.15 721.00 ± 111.54 0.078 4 th FET 714.22 ± 74.89 N/A Embryo cryopreservation 390.00 ± 189.91 434.27 ± 264.99 0.370 Miscarriage 84.68 ± 38.82 63.13 ± 31.83 0.277 OHSS N/A 134.53 § Total cost per patient 5125.57 ± 1018.15 5085.04 ± 844.78 0.696 # Abbreviations: COS: controlled ovarian stimulation; ET: embryo transfer; FET: frozen embryo transfer; GnRH: gonadotropin-releasing hormone; N/A: not applicable; OHSS: Ovarian hyperstimulation syndrome; OPU: ovum pick-up; PPOS: progestin-primed ovarian stimulation; USD: US dollar. Categorical data are expressed as percentages, and the between-group difference was examined using Chi-square test. Continuous data are reported as mean ± SD, and the between-group difference was evaluated using Student t test. # Wilcoxon rank sum test § Only one patient in the PPOS group experienced OHSS. The results of cost-effectiveness analysis for GnRH-ant against the PPOS protocol in CLBR are summarized in Table 5 . Numerically, the GnRH-ant protocol led to a higher CLBR (difference of 1.96%) and total cost per patient (difference of $40.53), yet a lower total cost per live birth (difference of −$256), yielding an ICER of $2067.14 per live birth when compared to PPOS. Table 5 . CLBRs and total costs associated with GnRH antagonist and PPOS. GnRH antagonist (n=255) PPOS (n=85) Difference CLBRs 56.08% 54.12% 1.96% Total cost per patient $5125.57 $5085.04 $40.53 Total cost per live birth $9140 $9396 $−256 ICER $2067.14 Abbreviations: CLBR: cumulative live birth rate; GnRH: gonadotropin-releasing hormone; ICER: incremental cost-effectiveness ratio; PPOS: progestin-primed ovarian stimulation. With PSA results distributed across the cost-effectiveness plane, 62.04% of simulations indicated GnRH-ant could be more effective than the PPOS protocol. Among these, 43.64% fell in quadrant I, suggesting that GnRH-ant provided greater effectiveness at an increased cost ( Figure 1A ). Conversely, 37.97% of simulations showed that GnRH-ant could be less effective than PPOS but had a 17.44% chance of also being less costly, making cost-effectiveness contingent on the WTP threshold. Two WTP thresholds, $2,000 and $10,000 per unit increase in live birth rate, are overlaid on the cost-effectiveness plane ( Figure 1B ). At a $2,000 WTP threshold, a relatively conservative cost-effectiveness criterion, approximately 40% of simulations fell below the line, suggesting a relatively low likelihood of the GnRH-ant strategy being considered cost-effective. However, when increasing the WTP threshold to $10,000, 58% of the simulations supported the GnRH-ant strategy, indicating a greater probability of cost-effectiveness under a more flexible decision-making framework. Figure 1C presents a CEAC derived from PSA simulations, showing that the probability of GnRH-ant being considered more cost-effective than PPOS increased to 61.3% at a WTP threshold of $30,000, underscoring economic trade-offs associated with the GnRH-ant treatment approach. DISCUSSION In this retrospective study, we compared the clinical and economic outcomes of GnRH-ant protocols and PPOS in achieving live births. Both protocols demonstrated comparable efficacy across most clinical outcomes, including oocyte retrieval rate, total mature oocytes, pregnancy rate, and CLBRs. Notably, the time from ovarian stimulation to live birth was significantly shorter by more than 40 days in patients receiving the GnRH-ant protocol compared to the PPOS group. This difference may be attributed to the option of fresh ET available with the GnRH-ant protocol but not with PPOS. Supporting the slightly higher CLBR observed with GnRH-ant, a higher mature oocyte rate was also recorded in this group compared to PPOS. Economically, there was no statistically significant difference between the two protocols in total cost per live birth, per patient, or by medical procedure. However, the ICER of GnRH-ant vs PPOS in achieving one live birth was estimated at $2,067.14. At a WTP threshold in the range of $5,000–10,000, the probability of GnRH-ant being more cost-effective than PPOS started to exceed 50%. This suggests that GnRH-ant may enable earlier and more cost-effective live births than PPOS, benefiting women seeking to conceive as soon as possible. Findings from previous meta-analyses generally align with our results. The most recent Cochrane review concluded that live birth and clinical pregnancy rates, as well as total and MII oocytes retrieved, showed minimal or no difference between GnRH-ant and progestin protocols. 11 Similarly, an earlier meta-analysis reported comparable live birth and pregnancy rates, regardless of donor or autologous oocytes, along with slightly higher total and mature oocyte counts in PPOS. 23 However, stimulation duration and total gonadotropin consumption were not found to differ between the two types of COS protocols. 23 Subsequent pooled analyses by the same research group largely confirmed no significant differences in ovarian stimulation and ET outcomes between these protocols after the inclusion of more studies. 24 In patients with polycystic ovarian syndrome, PPOS and GnRH-ant were equally effective in achieving retrieved oocytes, pregnancies, and live births. 25 Recent independent studies largely support these earlier findings across diverse patient populations. In women with normal or diminished ovarian reserve undergoing COS followed by fresh ET or FET, GnRH-ant demonstrated similar ovarian, pregnancy, and birth outcomes compared to PPOS. 26-28 Additionally, in patients classified as POSEIDON 1, GnRH-ant was associated with a shorter time from ovarian stimulation to live birth and a lower total gonadotropin dose. 26 For FET patients, findings were less consistent. Some studies reported no significant differences or favored GnRH-ant in pregnancy and live birth rates. Other studies found better total and mature oocyte numbers in PPOS-treated patients and longer stimulation durations. 29-31 For patients undergoing fertility preservation due to cancer or endometriosis, PPOS-based COS resulted in similar or lower numbers of total and mature oocytes retrieved compared to GnRH-ant, despite the GnRH-ant requiring more injections in one study. 16 , 19 , 32 In oocyte donor cycles, comparable numbers of total and mature oocytes were retrieved between GnRH-ant-treated and PPOS-treated donors, with recipients of embryos from fresh or thawed oocytes showing similar pregnancy and birth rates. 17 , 18 , 33-36 Interestingly, a study evaluating patients through two consecutive COS cycles, consisting of one GnRH-ant cycle followed by PPOS, found that total and mature oocytes retrieved were significantly fewer after the GnRH-ant cycle. 37 While many studies report total and mature oocyte counts after ovarian stimulation, mature oocyte rates are not consistently documented. In studies that did report total or mature oocyte numbers, mature oocyte rates were often comparable. One study found a significantly higher yield of total or mature oocytes in the PPOS group, while the maturation rate remained comparable. 29 Although outside the scope of our study, multiple factors, including patient demographics, AMH levels, type of gonadotropin, trigger method, and timing of oocyte retrieval, may contribute to ovarian response outcomes. 19 , 38 , 39 PPOS has been reported to prolong time to oocyte maturation, provide milder pituitary suppression, and better prevention for premature LH surges. 12 , 29 , 31 , 35 , 40 How these translate into clinical practice is debated, but the prevailing view is that ovarian response, oocyte competency, and retrieval time between GnRH-ant and PPOS protocols are largely similar, with no clinically significant differences. 36 , 41 , 42 Few studies have directly compared the real-world costs of GnRH-ant versus PPOS in achieving live births. Some evidence suggests that PPOS may be less costly per ovarian stimulation cycle in donor and fertility preservation cases. 16-20 A simulation study estimated that the cost per live birth with one fresh embryo transfer following GnRH-ant was significantly lower than that of one FET following PPOS, by approximately $4,447–12,797, with the cost advantage persisting when accounting for subsequent FET cycles. 15 In our study, CLBR in the GnRH-ant protocol was 1.98% higher than in the PPOS group, with a cost difference of $40.53, resulting in an ICER of $2,067 per additional live birth. Furthermore, the probability of GnRH-ant being more cost-effective exceeded 50% at WTP thresholds of US$5,000 and above. As of this manuscript's completion, no published cost-effectiveness analyses directly comparing the two COS protocols exists, regardless of the clinical endpoint used. A systematic review of economic evaluations of ART in high-income countries noted that while COS was the most frequently analyzed ART intervention, only one study specifically compared GnRH-ant and PPOS. 43 However, global fertility treatment costs vary widely, with the cost per live birth after one fresh ET ranging from $4,245 in South Korea to $12,314 in Australia. 44 While no consensus exists on WTP thresholds for fertility treatments, ICER remains the most commonly used cost-effectiveness measure. 45 Published WTP thresholds range from €2,945 for a 5% increase in live birth rates in the UK to €98,533 for one guaranteed live birth via ART in the US. 45 Our findings of costs per live birth slightly above $9,000 and per patient around $5,000 for both protocols align with these global estimates. Furthermore, the WTP thresholds used in our analysis not only encompass our ICER estimates but also align with those reported in the literature. Given similar CLBRs and modest cost differences found in our study, clinicians should consider both the economic metrics and clinical outcomes when formulating ART treatment strategies through shared decision-making. The current study has limitations that warrant discussion. Firstly, its retrospective design potentially introduces selection bias and confounding factors that may influence both efficacy and economic outcomes. The lack of prospective observation and randomization further limits causal interpretation. Additionally, as a single-center study conducted within one country, variations in clinical practice and healthcare costs may affect the generalizability of our findings. Lastly, patient preferences and quality of life, which are critical in treatment decision-making, were not assessed. Future multinational randomized trials addressing patient-centered factors are needed to validate and extend our findings. Conclusion This study compared the efficacy of GnRH-ant and PPOS protocols and is a first to evaluate their cost-effectiveness in CLBRs. Both protocols achieved similar pregnancy and live birth rates with comparable medical costs, though GnRH-ant was potentially more cost-effective at higher WTP thresholds. Additionally, GnRH-ant significantly shortened the time from ovarian stimulation to live birth. These findings suggest that GnRH-ant is a clinically and economically viable COS option, particularly for patients prioritizing a shorter time to live birth under a more flexible financial setting. Abbreviations ant, antagonist (as in GnRH-ant) AMH, anti-Müllerian hormone ART, assisted reproductive technology BMI, body mass index CEAC, cost-effectiveness acceptability curve CLBR , cumulative live birth rate COS, controlled ovarian stimulation ET, embryo transfer FET, frozen embryo transfer FSH, follicle-stimulating hormone GnRH-ant, gonadotropin-releasing hormone antagonist ICER, incremental cost-effectiveness ratio ICSI, intracytoplasmic sperm injection IVF, in vitro fertilization LB, live birth LH, luteinizing hormone N/A, not applicable OHSS, ovarian hyperstimulation syndrome OPU, ovum pick-up OS, ovarian stimulation PPOS, progestin-primed ovarian stimulation PSA, probabilistic sensitivity analysis USD, United States dollar WTP, willingness-to-pay Declarations Acknowledgements None. Author contributions Jui-Chun Chang: Investigation, Formal analysis, Writing - Original Draft, Writing - Review & Editing, Methodology, Project administration, Resources, Validation, Visualization Yu-Chiao Yi: Investigation, Writing - Original Draft, Project administration, Resources Hwa-Fen Guu: Investigation, Writing - Original Draft, Project administration, Resources Ya-Fang Chen: Investigation, Formal analysis, Writing - Original Draft, Methodology, Project administration, Resources, Visualization Li-Yu Chen: Investigation, Writing - Original Draft, Project administration, Resources Hsiao-Fan Kung: Investigation, Writing - Original Draft, Project administration, Resources Yu-Mei Chang: Formal analysis, Writing - Original Draft, Writing - Review & Editing, Methodology, Software, Visualization Ming-Jer Chen: Conceptualization, Investigation, Writing - Original Draft, Writing - Review & Editing, Methodology, Project administration, Resources, Supervision, Validation, Visualization Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study protocol was reviewed and approved by the Institutional Review Board of Taichung Veterans General Hospital (IRB: CE24607A), which waived the requirement for informed consent due to the retrospective nature of the study. This study was performed in adherence with the principles of the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare that they have no conflict of interest. Funding No funding was received for conducting this study. References Organization, W. H. Infertility prevalence estimates, 1990-2021 , https://iris.who.int/bitstream/handle/10665/366700/9789240068315-eng.pdf?sequence=1 (2023). European Society of Human Reproduction and Embryology. Factsheet on infertility - prevalence, treatment and fertility decline in Europe , https://www.eshre.eu/-/media/sitecore-files/ESHRE-internal/EU-Affairs/ESHRE_InfertilityFactsheet_April2024Final.pdf (2024). Kupka, M. S. et al. 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A. Comparing Progesterone Primed Ovarian Stimulation (PPOS) to GnRH Antagonist Protocol in Oocyte Donation Cycles. Journal of human reproductive sciences 15 , 278-283. https://doi.org/10.4103/jhrs.jhrs_85_22 (2022). Singh, E., Blockeel, C., Singh, M., Gupta, R. & Kamdi, S. Evaluation of pregnancy outcomes using medroxyprogesterone acetate versus gonadotropin-releasing hormone antagonist in ovarian stimulation: A retrospective cohort study. International journal of reproductive biomedicine 20 , 491-500. https://doi.org/10.18502/ijrm.v20i6.11445 (2022). Filippi, F. et al. Progestin-primed ovarian stimulation for fertility preservation in women with cancer: A comparative study. PloS one 18 , e0280238. https://doi.org/10.1371/journal.pone.0280238 (2023). Gonzalo, J., Castelo-Branco, C., Garcia, S., Devesa, M. & Polyzos, N. P. Economic impact of ovarian stimulation antagonist protocol vs primed progesterone protocol in oocyte donor program: A retrospective study. European Gynecology and Obstetrics 6 , 101-107. https://doi.org/10.53260/EGO.246033 (2024). Chang, J. C. et al. Does the "freeze-all" policy allow for a better outcome in assisted reproductive techniques than the use of fresh embryo transfers? - A retrospective study on cumulative live birth rates. Taiwanese journal of obstetrics & gynecology 56 , 775-780. https://doi.org/10.1016/j.tjog.2017.10.013 (2017). Chen, M. J. et al. Corrigendum: A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol. Frontiers in endocrinology 13 , 1099647. https://doi.org/10.3389/fendo.2022.1099647 (2022). Alexandru, P., Cekic, S. G., Yildiz, S., Turkgeldi, E. & Ata, B. Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis. Reproductive biomedicine online 40 , 894-903. https://doi.org/10.1016/j.rbmo.2020.01.027 (2020). Ata, B., Capuzzo, M., Turkgeldi, E., Yildiz, S. & La Marca, A. Progestins for pituitary suppression during ovarian stimulation for ART: a comprehensive and systematic review including meta-analyses. Human reproduction update 27 , 48-66. https://doi.org/10.1093/humupd/dmaa040 (2021). Yang, L. et al. Efficacy of progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization: a systematic review and meta-analysis. Frontiers in endocrinology 14 , 1224858. https://doi.org/10.3389/fendo.2023.1224858 (2023). Du, M. et al. Comparison of the Cumulative Live Birth Rates of Progestin-Primed Ovarian Stimulation and Flexible GnRH Antagonist Protocols in Patients With Low Prognosis. Frontiers in endocrinology 12 , 705264. https://doi.org/10.3389/fendo.2021.705264 (2021). Wang, M. et al. Comparison of progestin-primed ovarian stimulation regimen and antagonist regimen in women aged 35 years or older with diminished ovarian reserve: A propensity score-matched study. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 167 , 162-168. https://doi.org/10.1002/ijgo.15543 (2024). Ye, H. et al. Cumulative live birth rate of in vitro fertilization cycle via progestin-primed ovarian stimulation versus gonadotropin-releasing hormone antagonist protocol in infertile women with normal ovarian reserve: an open-label, randomized controlled trial. Human fertility 27 , 2316005. https://doi.org/10.1080/14647273.2024.2316005 (2024). Kalafat, E. et al. Outcomes of a GnRH Agonist Trigger Following a GnRH Antagonist or Flexible Progestin-Primed Ovarian Stimulation Cycle. Frontiers in endocrinology 13 , 837880. https://doi.org/10.3389/fendo.2022.837880 (2022). Huong, N. T. L. et al. Fewer good-quality cleavage embryos in dydrogesterone-primed ovarian stimulation compared to GnRH antagonist protocol in POSEIDON group 4 patients. Journal of the Formosan Medical Association = Taiwan yi zhi , S0929-6646(0925)00045-00042. https://doi.org/10.1016/j.jfma.2025.02.003 (2025). Handa, M. et al. Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single cell analysis. Reproductive biomedicine online , 104833. https://doi.org/10.1016/j.rbmo.2025.104833 (2025). Oliveira, R. et al. Fertility preservation in breast cancer with oral progestin: is it an option? A pilot study. Einstein 19 , eAO5859. https://doi.org/10.31744/einstein_journal/2021AO5859 (2021). Martinez, F. et al. Does LH suppression by progesterone-primed ovarian stimulation compared with GnRH antagonist affect live birth rate among oocyte recipients? Reproductive biomedicine online 40 , 661-667. https://doi.org/10.1016/j.rbmo.2020.01.016 (2020). Devesa, M. et al. Progesterone-primed ovarian stimulation in oocyte donation: a model for elective fertility preservation? Reproductive biomedicine online 44 , 1015-1022. https://doi.org/10.1016/j.rbmo.2022.02.003 (2022). Kao, T. C. et al. Progestin-primed ovarian stimulation versus GnRH antagonist protocol in poor responders: Risk of premature LH surge and outcome of oocyte retrieval. Journal of the Formosan Medical Association = Taiwan yi zhi 122 , 29-35. https://doi.org/10.1016/j.jfma.2022.08.023 (2023). Vaiarelli, A. et al. Oocyte competence is comparable between progestin primed ovarian stimulation with Norethisterone acetate (NETA-PPOS) and GnRH-antagonist protocols: A matched case-control study in PGT-A cycles. European journal of obstetrics, gynecology, and reproductive biology 294 , 4-10. https://doi.org/10.1016/j.ejogrb.2023.12.035 (2024). Vidal, M. D. M., Martinez, F., Rodriguez, I. & Polyzos, N. P. Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles. Human reproduction 39 , 1098-1104. https://doi.org/10.1093/humrep/deae047 (2024). Meyer, L. et al. Risk factors for a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles. Fertility and sterility 104 , 637-642. https://doi.org/10.1016/j.fertnstert.2015.06.011 (2015). Bosch, E. et al. Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists--a randomized study. Human reproduction 23 , 2346-2351. https://doi.org/10.1093/humrep/den220 (2008). Xie, Y. et al. A delayed ovulation of progestin-primed ovarian stimulation (PPOS) by downregulating the LHCGR/PGR pathway. iScience 26 , 107357. https://doi.org/10.1016/j.isci.2023.107357 (2023). Ata, B. et al. Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles? Reproductive biomedicine online 48 , 103626. https://doi.org/10.1016/j.rbmo.2023.103626 (2024). Ata, B. & Kalafat, E. Progestin-primed ovarian stimulation: for whom, when and how? Reproductive biomedicine online 48 , 103639. https://doi.org/10.1016/j.rbmo.2023.103639 (2024). Olive, E. et al. Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review. Human reproduction 39 , 981-991. https://doi.org/10.1093/humrep/deae039 (2024). Matorras, R. et al. Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective. Best practice & research. Clinical obstetrics & gynaecology 89 , 102349. https://doi.org/10.1016/j.bpobgyn.2023.102349 (2023). Fenwick, E. et al. The value of treatment for infertility: A systematic literature review of willingness-to-pay thresholds and approaches for determining the cost effectiveness of fertility therapies. Best practice & research. Clinical obstetrics & gynaecology 89 , 102340. https://doi.org/10.1016/j.bpobgyn.2023.102340 (2023). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6803353","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":466867066,"identity":"422a7759-58ed-4f49-84be-83aa3ae8571c","order_by":0,"name":"Jui-Chun Chang","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jui-Chun","middleName":"","lastName":"Chang","suffix":""},{"id":466867067,"identity":"56a2393b-6915-4622-8fbe-46d98bc9b2e3","order_by":1,"name":"Yu-Chiao Yi","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu-Chiao","middleName":"","lastName":"Yi","suffix":""},{"id":466867068,"identity":"ff4e12d5-581c-40b9-9e26-5bf9770005b2","order_by":2,"name":"Hwa-Fen Guu","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hwa-Fen","middleName":"","lastName":"Guu","suffix":""},{"id":466867069,"identity":"fdade5a5-18b9-4be3-87b3-7eb802b8076a","order_by":3,"name":"Ya-Fang Chen","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ya-Fang","middleName":"","lastName":"Chen","suffix":""},{"id":466867070,"identity":"ac71ce93-36bf-42c9-a19c-1b491a4ee5e0","order_by":4,"name":"Li-Yu Chen","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li-Yu","middleName":"","lastName":"Chen","suffix":""},{"id":466867071,"identity":"dee7af5c-6429-486e-bd19-8575da77d32f","order_by":5,"name":"Hsiao-Fan Kung","email":"","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hsiao-Fan","middleName":"","lastName":"Kung","suffix":""},{"id":466867072,"identity":"0c4fd7b6-f5cc-4ede-86aa-a8f4e4ba3c9d","order_by":6,"name":"Yu-Mei Chang","email":"","orcid":"","institution":"Tunghai University","correspondingAuthor":false,"prefix":"","firstName":"Yu-Mei","middleName":"","lastName":"Chang","suffix":""},{"id":466867073,"identity":"468a929c-52e1-4844-ac8b-0e8cb3386c77","order_by":7,"name":"Ming-Jer Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDACZiCWAGIDBgbGB0Cah48ULcwGIC1sRNsGVM4G0spAUItuO+/hFxYV9+TN2XuPVX7NsZNhY2B++OgGHi1mh/nSLCTOFBvu7DmXdlt2WzLQYWzGxjl4tfCYGUi2JSQY3Mgxuy25jRmohYdNmrCWf0At99+YFUtuqydKi/EDyQaQLTxmjB+3HSbOFgaJYwmGG87kGEszbjvOw8ZMyC/nzxh/lqhJkDc4fsbw489t1fb87M0PH+PTAgRs0hJQFjMPmMSvHKzk4wcoi/EHYdWjYBSMglEwAgEAVKRCXkUvTGMAAAAASUVORK5CYII=","orcid":"","institution":"Taichung Veterans General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ming-Jer","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-06-02 14:53:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6803353/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6803353/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84339225,"identity":"9e5c6ce9-adb8-4a01-937d-2ff9450ccd72","added_by":"auto","created_at":"2025-06-10 18:13:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":153793,"visible":true,"origin":"","legend":"\u003cp\u003eProbabilistic sensitivity analysis.\u003c/p\u003e\n\u003cp\u003e(A) Cost-effectiveness plane showing the incremental cost-effectiveness ratio of GnRH antagonist over PPOS for cumulative live births. (B) Cost-effectiveness plane with willingness-to-pay thresholds.(C) Cost-effectiveness acceptability curve for cumulative live birth.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6803353/v1/1901cc6affe5b5883440e4f1.png"},{"id":87250695,"identity":"4546e3f1-c447-461d-a31b-12474b0cb265","added_by":"auto","created_at":"2025-07-22 04:23:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1110653,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6803353/v1/1924e397-5797-41ea-9714-899cf6b0255a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Cumulative Live Birth Rates and Cost-Effectiveness Between GnRH Antagonist and Progestin-Primed Ovarian Stimulation Protocols Running title: Cost-effectiveness of GnRH-ant vs PPOS","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eInfertility, defined as the inability to conceive after more than one year of regular unprotected intercourse, affects approximately one in six individuals worldwide.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The estimated global lifetime prevalence of infertility is 17.5%, with higher regional prevalence reported in the Western Pacific (23.2%) and the Americas (20.0%).\u003csup\u003e1\u003c/sup\u003e Reflecting these trends, the European Society of Human Reproduction and Embryology reported that in 2021, the total fertility rate in the EU was 1.53 births per woman, with nearly 3% of all births resulting from assisted reproductive technologies (ART).\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Approximately one-third of all ART cycles worldwide were initiated in Europe, yielding a cumulative live birth rate (CLBR) of 31.4% per aspiration.\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e While Japan, China, and the US were among the most active countries in ART utilization, Taiwan demonstrated relatively high ART accessibility, performing an estimated 2,104 cycles per million population.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e This underscores the significance of the country\u0026rsquo;s ART experience in the Asia-Pacific region and globally.\u003c/p\u003e \u003cp\u003eControlled ovarian stimulation (COS) is a critical component of ART and fertility preservation treatments. COS typically involves follicular development stimulation, pituitary suppression, which prevents premature luteinizing hormone (LH) surges and enables controlled oocyte retrieval. This is followed by oocyte maturation triggering.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Gonadotropin-releasing hormone antagonists (GnRH-ant) are favored over gonadotropin-releasing hormone agonists for COS by guidelines and expert consensus due to similar live birth rates but a lower risk of ovarian hyperstimulation syndrome (OHSS).\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In contrast to GnRH analogues, the progestin-primed ovarian stimulation (PPOS) protocol has gained attention over the past decade as an alternative for preventing premature LH surges.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e However, due to the limited availability of randomized controlled trials directly comparing GnRH analogues and PPOS, evidence-based analyses regarding their relative clinical efficacy remain inconclusive.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMechanistically, progestin exposure during the follicular phase induces premature endometrial advancement and asynchrony, precluding fresh embryo transfer (ET) within the same COS cycle.\u003csup\u003e\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e There is also ongoing debate regarding the effects of COS protocols on oocyte quality and retrieval timing,\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e both of which may impact pregnancy and live birth rates. Consequently, clinical guidelines recommend limiting PPOS to cycles with planned freeze-all strategy,\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e favoring GnRH analogues when fresh ET is intended.\u003c/p\u003e \u003cp\u003eDespite growing interest, cost-effectiveness studies comparing GnRH-ant and PPOS remain scarce. Existing analyses often vary in clinical efficacy endpoints, such as live birth rates and oocyte yield, or relying on simulation-based models.\u003csup\u003e\u003cspan additionalcitationids=\"CR16 CR17 CR18 CR19\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e In this study, we aim to compare cumulative live birth rates (CLBRs) and cost-effectiveness of GnRH-ant versus PPOS using real world and as-it-occurred data. The cost-effectiveness of two protocols was evaluated through incremental cost-effectiveness ratio (ICER) analysis and willingness-to-pay (WTP) thresholds for achieving a live birth.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and study population\u003c/h2\u003e \u003cp\u003e This retrospective study included women who underwent COS using either the GnRH-ant or PPOS protocol, followed by fresh ET and/or frozen embryo transfer (FET) at Taichung Veterans General Hospital, Taiwan, between 2018 and 2022. Exclusion criteria were: i) use of preimplantation genetic diagnosis and/or screening and, ii) failure to produce usable embryos after COS. Eligible participants were matched in a 3:1 ratio propensity score (GnRH-ant: PPOS) based on age and anti-M\u0026uuml;llerian hormone (AMH) levels. The study protocol was reviewed and approved by the Institutional Review Board of Taichung Veterans General Hospital (IRB: CE24607A), and the requirement for informed consent was waived by the Institutional Review Board of Taichung Veterans General Hospital due to the retrospective nature of the study. This study was performed in adherence with the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCOS protocol\u003c/h3\u003e\n\u003cp\u003eOvarian stimulation began on menstrual cycle day 2 or 3 with the administration of 150\u0026ndash;300 IU/day of recombinant human follicle-stimulating hormone (r-hFSH; Gonal-F) plus human menopausal gonadotropin (hMG; Menopur, 150\u0026ndash;300 IU/day, providing both FSH and LH activity) or r-hFSH (150\u0026ndash;300 IU/day) plus recombinant human luteinizing hormone (r-hLH; 75\u0026ndash;150 IU/day) (Pergoveris, Merck-Serono, Germany). Dosage was adjusted based on patient response and physician discretion. For the GnRH-ant protocol, pituitary suppression was achieved with GnRH-ant (Cetrotide, 0.25 mg/day) in a flexible protocol, initiated when the dominant follicle reached 12\u0026ndash;14 mm in diameter and continued until the trigger day. For the PPOS protocol, progestin (Provera, 5 mg twice daily) was administered from the start of stimulation until the trigger day. Ovulation was triggered when \u0026ge;\u0026thinsp;3 dominant follicles reached an average diameter of \u0026gt;\u0026thinsp;17 mm using recombinant human chorionic gonadotropin (hCG) (Ovidrel, 250 \u0026micro;g) and/or GnRH agonist (Decapeptyl, 0.2 mg). Dual triggering has been a routine practice at the study site since 2014, except for high-risk OHSS patients, for whom GnRH agonist was used, and subsequent fresh ET was canceled. Oocyte retrieval occurred 35\u0026ndash;37 hours post-trigger.\u003c/p\u003e\n\u003ch3\u003eFertilization, ET, and clinical outcomes\u003c/h3\u003e\n\u003cp\u003eOocytes were fertilized via \u003cem\u003ein vitro\u003c/em\u003e fertilization or intracytoplasmic sperm injection 4\u0026ndash;6 hours after retrieval. In fresh cycles, day 2 or day 3 embryos or day 5 blastocysts were transferred, while surplus embryos or blastocysts were vitrified. Each ET involved 1\u0026ndash;4 fresh or frozen embryos, depending on the patient\u0026rsquo;s conditions. Luteal support for fresh ET, endometrial preparations for FET, and embryo thawing were performed as previously prescribed.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e A complete ART cycle included one fresh ET and/or up to 4 FET. Pregnancy was confirmed by a positive β-hCG serum level tested 9\u0026ndash;12 days after ET. Live birth was defined as the delivery of a live infant after a minimum of 24 gestational weeks. CLBR was defined as the first live birth achieved from one aspirated cycle, including all ETs until all embryos were used.\u003c/p\u003e\n\u003ch3\u003eData collection and cost-effective analysis\u003c/h3\u003e\n\u003cp\u003eDemographic, laboratory, clinical, and cost-related data were retrieved from hospital records. The medical costs associated with ART \u0026mdash; including COS, hormone and ultrasound monitoring, oocyte retrieval, fresh ET, FET, embryo cryopreservation, miscarriage, and OHSS \u0026mdash; were analyzed. Childbirth costs were excluded, as not all women delivered their infants at the study site.\u003c/p\u003e \u003cp\u003eCost-effectiveness was assessed by calculating ICER, comparing the additional costs of the GnRH-ant protocol to PPOS in relation to the difference in CLBR. Incremental cost represents the difference in expenses per patient when choosing GnRH-ant over PPOS, while incremental effectiveness reflects the percentage increase in CLBR with GnRH-ant.\u003c/p\u003e \u003cp\u003eProbabilistic sensitivity analysis (PSA) was performed using Monte Carlo simulation with 50,000 bootstrap iterations using the R package (v4.4.1). A cost-effectiveness plane was used, and a cost-effectiveness acceptability curve (CEAC) was generated to illustrate the probability of the GnRH-ant protocol being cost-effective across various WTP thresholds.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed on an intention-to-treat basis. Continuous variables were presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations and analyzed using the Mann-Whitney U test or Wilcoxon rank-sum test. Categorical variables were expressed as counts and percentages, analyzed using the Chi-square test. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003ePatient demographics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter applying eligibility criteria and propensity matching, a total of 225 women who underwent COS with the GnRH antagonist protocol and 85 with PPOS were included in this retrospective study. The two groups had comparable baseline demographics and clinical characteristics, including age (36.49 \u0026plusmn; 3.61 vs 36.49 \u0026plusmn; 3.62 years), body mass index (22.78 \u0026plusmn; 3.67 vs 23.04 \u0026plusmn; 3.88 kg/m\u003csup\u003e2\u003c/sup\u003e), duration of infertility (3.38 \u0026plusmn; 2.52 vs 3.66 \u0026plusmn; 2.72 years), and infertility type and cause (all p \u0026gt; 0.05, \u003cstrong\u003eTable 1\u003c/strong\u003e). Basal levels of AMH, FSH, and fertilization methods were also similar between patients who received GnRH-ant and PPOS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Baseline clinical characteristics of patients using GnRH antagonist and PPOS after propensity score matching.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003eGnRH antagonist (n=255)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003ePPOS\u003c/p\u003e\n \u003cp\u003e(n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e36.49 \u0026plusmn; 3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e36.49 \u0026plusmn; 3.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eAMH (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e2.28 \u0026plusmn; 1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e2.29 \u0026plusmn; 1.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.943\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e22.78 \u0026plusmn; 3.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e23.04 \u0026plusmn; 3.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.634\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eDuration of Infertility (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e3.38 \u0026plusmn; 2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e3.66 \u0026plusmn; 2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.452\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eInfertility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.445\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e102 (40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e38 (44.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eSecondary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e153 (60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e47 (55.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eBasal FSH (IU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e7.02 \u0026plusmn; 2.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e6.33 \u0026plusmn; 3.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.061\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eCause of infertility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eTubal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e47.0 (18.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e20.0 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eMale factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e24.0 (9.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e3.0 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eAnovulatory or diminished ovarian reserve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e70.0 (27.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e15.0 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eUnexplained\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e23.0 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e5.0 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eEndometriosis/adenomyosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e31.0 (12.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e20.0 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eMixed factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e11.0 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e4.0 (4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 36px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e48.0 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e18.0 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eFertilization method\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e185.0 (72.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e57.0 (67.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e50.0 (19.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e23.0 (27.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eBoth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e20.0 (7.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e5.0 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: AMH: anti-Mullerian hormone; BMI: body mass index; FSH: follicle-stimulating hormone; GnRH: gonadotropin -releasing hormone; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; PPOS: progestin-primed ovarian stimulation.\u003c/p\u003e\n\u003cp\u003eThe analysis cohort was matched at 3 vs 1 (GnRH antagonist vs PPOS) for baseline age and AMH.\u003c/p\u003e\n\u003cp\u003eContinuous data are reported as mean \u0026plusmn; standard deviation, and the between-group difference was evaluated using Mann-Whitney U test. Categorical data are expressed as counts (percentages), and the between-group difference was examined using Chi-square test or Fisher\u0026rsquo;s exact test.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOvarian response and clinical efficacy outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDifferences in ovarian response to COS are summarized in \u003cstrong\u003eTable 2\u003c/strong\u003e. Compared to PPOS, the GnRH-ant protocol had significantly lower total FSH (3310.53 \u0026plusmn; 1118.14 vs 3612.81\u0026plusmn; 1311.00 IU, \u003cem\u003ep\u003c/em\u003e = 0.033) and LH dosage (1147.94 \u0026plusmn; 680.59 vs 1413.09 \u0026plusmn; 705.52 IU, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), shorter stimulation duration (10.04 \u0026plusmn; 1.54 vs 10.56 \u0026plusmn; 1.71 days, p = 0.015), greater endometrial thickness on trigger day (11.55 \u0026plusmn; 2.66 vs 8.85 \u0026plusmn; 2.57 mm, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and higher oocyte maturation rate (0.78 \u0026plusmn; 0.19 vs 0.69 \u0026plusmn; 0.19, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). Overall, OHSS incidence was low without statistically significant intergroup difference, with one moderate to severe case occurring in the PPOS group and none with GnRH-ant. The number of follicles \u0026ge; 18mm and fertility hormones on trigger day, number of fertilized oocytes, oocyte fertilization rate, number of good-quality embryos on day 3, good-quality embryo rate on day 3, number of total blastocysts, blastocyst formation rate, number of good blastocysts (\u0026gt;3BB), good blastocyst rate, and number of embryos transferred did not differ significantly between the groups. Compared to PPOS, despite a lower incidence of day 5 blastocysts selected for the first ET in the GnRH-ant group (55.7% vs 84.7%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), pregnancy (57.6% vs 48.6%) and live birth rates (44.7% vs 39.6%) after the first ET did not differ significantly between the two groups (all \u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05). The weeks of delivery, preterm delivery (\u0026lt;37 weeks), and birth weights did not show significant differences between the two groups (all \u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eOvarian and embryo transfer outcomes between GnRH antagonist and PPOS protocols after propensity score matching.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGnRH antagonist (n=255)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePPOS\u003c/p\u003e\n \u003cp\u003e(n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDosage of FSH (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3310.53 \u0026plusmn;\u0026nbsp;1118.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3612.81 \u0026plusmn;\u0026nbsp;1311.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDosage of LH (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1147.94 \u0026plusmn;\u0026nbsp;680.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1413.09 \u0026plusmn;\u0026nbsp;705.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDays of stimulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.04 \u0026plusmn;\u0026nbsp;1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.56 \u0026plusmn;\u0026nbsp;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOn the trigger day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFollicle size \u0026ge; 18mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.92 \u0026plusmn;\u0026nbsp;1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.09 \u0026plusmn;\u0026nbsp;1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEndometrial thickness (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.55 \u0026plusmn;\u0026nbsp;2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.85 \u0026plusmn;\u0026nbsp;2.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEstradiol (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2614.28 \u0026plusmn;\u0026nbsp;1756.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2814.87 \u0026plusmn;\u0026nbsp;2259.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.959\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLH (IU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.69 \u0026plusmn;\u0026nbsp;1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.66 \u0026plusmn;\u0026nbsp;1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.579\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eProgesterone (ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.89 \u0026plusmn;\u0026nbsp;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.88 \u0026plusmn;\u0026nbsp;0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.876\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNumber of retrieved oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.44 \u0026plusmn;\u0026nbsp;7.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13.14 \u0026plusmn; 10.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.299\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOocyte retrieval rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.92 \u0026plusmn; 0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.98 \u0026plusmn; 0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNumber of mature oocyte\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.71 \u0026plusmn; 5.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.66 \u0026plusmn; 6.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMaturation rate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.78 \u0026plusmn;\u0026nbsp;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.69 \u0026plusmn;\u0026nbsp;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOHSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.250\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNo or mild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e255 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e84 (98.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eModerate or severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNumber of fertilized oocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.99 \u0026plusmn;\u0026nbsp;5.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9.05 \u0026plusmn; 7.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.331\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOocyte fertilization rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.73 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.71 \u0026plusmn; 0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.300\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGood-quality embryos on day 3 \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.07 \u0026plusmn; 2.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.28 \u0026plusmn; 3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.628\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGood quality embryo rate on day 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.35 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.32 \u0026plusmn; 0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.099\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNumber of total blastocyst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.21 \u0026plusmn; 4.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.01 \u0026plusmn; 5.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBlastocyst formation rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.57 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.58 \u0026plusmn; 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.861\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNumber of good blastocyst\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.56 \u0026plusmn; 3.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.49 \u0026plusmn; 4.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGood blastocyst rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.66 \u0026plusmn; 0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.66 \u0026plusmn; 0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNumber of embryos transferred\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.264\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e99 (38.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e125 (49.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52 (61.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23 (9.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (8.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDay of embryo at 1\u003csup\u003est\u003c/sup\u003e embryo transfer\u0026Dagger;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDay 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36 (14.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (8.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDay 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e77 (30.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDay 5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e142 (55.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72 (84.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePregnancy rate of 1\u003csup\u003est\u003c/sup\u003e embryo transfer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e124 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e49 (57.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLive birth rate of 1\u003csup\u003est\u003c/sup\u003e embryo transfer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e101 (39.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e38 (44.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.408\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWeeks of delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e37.31 \u0026plusmn; 2.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36.84 \u0026plusmn; 3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.547\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePreterm (\u0026lt;37 weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBirth weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2861.68 \u0026plusmn; 578.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2718.89 \u0026plusmn; 760.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026dagger;Good-quality embryos = Grade 1 and Grade 2\u003c/p\u003e\n\u003cp\u003e\u0026Dagger;Including fresh and frozen embryo transfer.\u003c/p\u003e\n\u003cp\u003e\u0026sect;Good blastocyst on day 5 = 3AB, 3BA, and 4 to 6.\u003c/p\u003e\n\u003cp\u003eAbbreviations: FSH: follicle-stimulating hormone; GnRH: gonadotropin-releasing hormone; LH: luteinizing hormone; OHSS: ovarian hyperstimulation syndrome;\u0026nbsp;PPOS: progestin-primed ovarian stimulation.\u003c/p\u003e\n\u003cp\u003eContinuous data are reported as mean \u0026plusmn; standard deviation, and the between-group difference was evaluated using Mann-Whitney U test. Categorical data are expressed as counts (percentages), and the between-group difference was examined using Chi-square test or \u003csup\u003e#\u003c/sup\u003eFisher\u0026rsquo;s exact test.\u003c/p\u003e\n\u003cp\u003eAs shown in \u003cstrong\u003eTable 3\u003c/strong\u003e, the time from ovarian stimulation to LB was significantly shorter in the GnRH-ant group compared to PPOS (351.28 \u0026plusmn; 138.59 vs 394.42 \u0026plusmn; 105.90 days, p \u0026lt;0.001). CLBR tended to be higher (56.08% vs 54.12%) and time from ET to LB shorter (248.60 \u0026plusmn; 17.06 vs 260.87 \u0026plusmn; 77.44 days) for the GnRH-ant group compared to PPOS, though the difference was not statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eComparison of CLBRs and time to LB between the GnRH antagonist and PPOS groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eVariables\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003eGnRH antagonist (n=255)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003ePPOS\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eCLBRs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e143/255 (56.08%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e46/85 (54.12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.850\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eTime from OS to LB (day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e351.28 \u0026plusmn;\u0026nbsp;138.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e394.42 \u0026plusmn;\u0026nbsp;105.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eTime from ET to LB (day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 28px;\"\u003e\n \u003cp\u003e248.60 \u0026plusmn;\u0026nbsp;17.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e260.87 \u0026plusmn;\u0026nbsp;77.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.718\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CLBR: cumulative live birth rate; ET: embryo transfer; GnRH: gonadotropin hormone-releasing hormone; LB: live birth; OS: ovarian stimulation; PPOS: progestin-primed ovarian stimulation.\u003c/p\u003e\n\u003cp\u003eCategorical data are expressed as percentages, and the between-group difference was examined using Chi square test. Continuous data are reported as mean \u0026plusmn; SD, and the between-group difference was evaluated using Mann-Whitney U test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCost-effectiveness and sensitivity analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll medical costs, by procedure or in total, were comparable between the GnRH-ant and PPOS protocols, with the total cost per patient similar between the two protocols ($5125.57 \u0026plusmn; 1018.15 vs $5085.04 \u0026plusmn; 844.78, p\u0026gt;0.05) (\u003cstrong\u003eTable 4\u003c/strong\u003e). Costs for fresh ET and 4\u003csup\u003eth\u003c/sup\u003e FET were incurred only in the GnRH-ant group, while OHSS-related costs were exclusive to the PPOS group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Mean medical costs associated with the GnRH antagonist and PPOS protocols.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eType of cost (USD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eGnRH antagonist (n=255)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003ePPOS (n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eCOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e1991.88\u0026nbsp;\u0026plusmn; 582.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e1867.31\u0026nbsp;\u0026plusmn; 685.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eHormonal test and sonography\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e136.51\u0026nbsp;\u0026plusmn; 28.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e138.08\u0026nbsp;\u0026plusmn; 24.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eOPU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e1581.81\u0026nbsp;\u0026plusmn; 202.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e1608.22\u0026nbsp;\u0026plusmn; 214.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eFresh ET \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e598.21\u0026nbsp;\u0026plusmn; 233.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e1\u003csup\u003est\u003c/sup\u003e FET\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e942.56\u0026nbsp;\u0026plusmn; 326.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e842.71\u0026nbsp;\u0026plusmn; 236.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e2\u003csup\u003end\u003c/sup\u003e FET\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e857.45\u0026nbsp;\u0026plusmn; 241.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e755.51\u0026nbsp;\u0026plusmn; 99.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e3\u003csup\u003erd\u003c/sup\u003e FET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e942.10\u0026nbsp;\u0026plusmn; 318.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e721.00\u0026nbsp;\u0026plusmn; 111.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003e4\u003csup\u003eth\u003c/sup\u003e FET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e714.22\u0026nbsp;\u0026plusmn; 74.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eEmbryo cryopreservation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e390.00\u0026nbsp;\u0026plusmn; 189.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e434.27\u0026nbsp;\u0026plusmn; 264.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eMiscarriage\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e84.68\u0026nbsp;\u0026plusmn; 38.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e63.13\u0026nbsp;\u0026plusmn; 31.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.277\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eOHSS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e134.53\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 31px;\"\u003e\n \u003cp\u003eTotal cost per patient\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e5125.57\u0026nbsp;\u0026plusmn; 1018.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27px;\"\u003e\n \u003cp\u003e5085.04\u0026nbsp;\u0026plusmn; 844.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.696\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations:\u0026nbsp;COS: controlled ovarian stimulation; ET: embryo transfer; FET: frozen embryo transfer; GnRH: gonadotropin-releasing hormone; N/A: not applicable; OHSS: Ovarian hyperstimulation syndrome;\u0026nbsp;OPU: ovum pick-up; PPOS: progestin-primed ovarian stimulation; USD: US dollar.\u003c/p\u003e\n\u003cp\u003eCategorical data are expressed as percentages, and the between-group difference was examined using Chi-square test. Continuous data are reported as mean \u0026plusmn; SD, and the between-group difference was evaluated using Student t test.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u003c/sup\u003eWilcoxon rank sum test\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eOnly one patient in the PPOS group experienced OHSS.\u003c/p\u003e\n\u003cp\u003eThe results of cost-effectiveness analysis for GnRH-ant against the PPOS protocol in CLBR are summarized in \u003cstrong\u003eTable 5\u003c/strong\u003e. Numerically, the GnRH-ant protocol led to a higher CLBR (difference of 1.96%) and total cost per patient (difference of $40.53), yet a lower total cost per live birth (difference of \u0026minus;$256), yielding an ICER of $2067.14 per live birth when compared to PPOS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e. CLBRs and total costs associated with GnRH antagonist and PPOS.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eGnRH antagonist\u003c/p\u003e\n \u003cp\u003e(n=255)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003ePPOS\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003eDifference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003eCLBRs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e56.08%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e54.12%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e1.96%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003eTotal cost per patient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e$5125.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e$5085.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e$40.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003eTotal cost per live birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e$9140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e$9396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e$\u0026minus;256\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003eICER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e$2067.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CLBR: cumulative live birth rate; GnRH: gonadotropin-releasing hormone; ICER: incremental cost-effectiveness ratio; PPOS: progestin-primed ovarian stimulation.\u003c/p\u003e\n\u003cp\u003eWith PSA results distributed across the cost-effectiveness plane, 62.04% of simulations indicated GnRH-ant could be more effective than the PPOS protocol. Among these, 43.64% fell in quadrant I, suggesting that GnRH-ant provided greater effectiveness at an increased cost (\u003cstrong\u003eFigure 1A\u003c/strong\u003e). Conversely, 37.97% of simulations showed that GnRH-ant could be less effective than PPOS but had a 17.44% chance of also being less costly, making cost-effectiveness contingent on the WTP threshold. Two WTP thresholds, $2,000 and $10,000 per unit increase in live birth rate, are overlaid on the cost-effectiveness plane (\u003cstrong\u003eFigure 1B\u003c/strong\u003e). At a $2,000 WTP threshold, a relatively conservative cost-effectiveness criterion, approximately 40% of simulations fell below the line, suggesting a relatively low likelihood of the GnRH-ant strategy being considered cost-effective. However, when increasing the WTP threshold to $10,000, 58% of the simulations supported the GnRH-ant strategy, indicating a greater probability of cost-effectiveness under a more flexible decision-making framework.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1C\u003c/strong\u003e presents a CEAC derived from PSA simulations, showing that the probability of GnRH-ant being considered more cost-effective than PPOS increased to 61.3% at a WTP threshold of $30,000, underscoring economic trade-offs associated with the GnRH-ant treatment approach.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this retrospective study, we compared the clinical and economic outcomes of GnRH-ant protocols and PPOS in achieving live births. Both protocols demonstrated comparable efficacy across most clinical outcomes, including oocyte retrieval rate, total mature oocytes, pregnancy rate, and CLBRs. Notably, the time from ovarian stimulation to live birth was significantly shorter by more than 40 days in patients receiving the GnRH-ant protocol compared to the PPOS group. This difference may be attributed to the option of fresh ET available with the GnRH-ant protocol but not with PPOS. Supporting the slightly higher CLBR observed with GnRH-ant, a higher mature oocyte rate was also recorded in this group compared to PPOS. Economically, there was no statistically significant difference between the two protocols in total cost per live birth, per patient, or by medical procedure. However, the ICER of GnRH-ant vs PPOS in achieving one live birth was estimated at $2,067.14. At a WTP threshold in the range of $5,000–10,000, the probability of GnRH-ant being more cost-effective than PPOS started to exceed 50%. This suggests that GnRH-ant may enable earlier and more cost-effective live births than PPOS, benefiting women seeking to conceive as soon as possible.\u003c/p\u003e\n\u003cp\u003eFindings from previous meta-analyses generally align with our results. The most recent Cochrane review concluded that live birth and clinical pregnancy rates, as well as total and MII oocytes retrieved, showed minimal or no difference between GnRH-ant and progestin protocols.\u003csup\u003e11\u003c/sup\u003e Similarly, an earlier meta-analysis reported comparable live birth and pregnancy rates, regardless of donor or autologous oocytes, along with slightly higher total and mature oocyte counts in PPOS.\u003csup\u003e23\u003c/sup\u003e However, stimulation duration and total gonadotropin consumption were not found to differ between the two types of COS protocols.\u003csup\u003e23\u003c/sup\u003e Subsequent pooled analyses by the same research group largely confirmed no significant differences in ovarian stimulation and ET outcomes between these protocols after the inclusion of more studies.\u003csup\u003e24\u003c/sup\u003e In patients with polycystic ovarian syndrome, PPOS and GnRH-ant were equally effective in achieving retrieved oocytes, pregnancies, and live births.\u003csup\u003e25\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eRecent independent studies largely support these earlier findings across diverse patient populations. In women with normal or diminished ovarian reserve undergoing COS followed by fresh ET or FET, GnRH-ant demonstrated similar ovarian, pregnancy, and birth outcomes compared to PPOS.\u003csup\u003e26-28\u003c/sup\u003e Additionally, in patients classified as POSEIDON 1, GnRH-ant was associated with a shorter time from ovarian stimulation to live birth and a lower total gonadotropin dose.\u003csup\u003e26\u003c/sup\u003e For FET patients, findings were less consistent. Some studies reported no significant differences or favored GnRH-ant in pregnancy and live birth rates. Other studies found better total and mature oocyte numbers in PPOS-treated patients and longer stimulation durations.\u003csup\u003e29-31\u003c/sup\u003e For patients undergoing fertility preservation due to cancer or endometriosis, PPOS-based COS resulted in similar or lower numbers of total and mature oocytes retrieved compared to GnRH-ant, despite the GnRH-ant requiring more injections in one study.\u003csup\u003e16\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e19\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e32\u003c/sup\u003e In oocyte donor cycles, comparable numbers of total and mature oocytes were retrieved between GnRH-ant-treated and PPOS-treated donors, with recipients of embryos from fresh or thawed oocytes showing similar pregnancy and birth rates.\u003csup\u003e17\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e18\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e33-36\u003c/sup\u003e Interestingly, a study evaluating patients through two consecutive COS cycles, consisting of one GnRH-ant cycle followed by PPOS, found that total and mature oocytes retrieved were significantly fewer after the GnRH-ant cycle.\u003csup\u003e37\u003c/sup\u003e \u003c/p\u003e\n\u003cp\u003eWhile many studies report total and mature oocyte counts after ovarian stimulation, mature oocyte rates are not consistently documented. In studies that did report total or mature oocyte numbers, mature oocyte rates were often comparable. One study found a significantly higher yield of total or mature oocytes in the PPOS group, while the maturation rate remained comparable. \u003csup\u003e29\u003c/sup\u003e Although outside the scope of our study, multiple factors, including patient demographics, AMH levels, type of gonadotropin, trigger method, and timing of oocyte retrieval, may contribute to ovarian response outcomes.\u003csup\u003e19\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e38\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e39\u003c/sup\u003e PPOS has been reported to prolong time to oocyte maturation, provide milder pituitary suppression, and better prevention for premature LH surges.\u003csup\u003e12\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e29\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e31\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e35\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e40\u003c/sup\u003e How these translate into clinical practice is debated, but the prevailing view is that ovarian response, oocyte competency, and retrieval time between GnRH-ant and PPOS protocols are largely similar, with no clinically significant differences.\u003csup\u003e36\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e41\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e42\u003c/sup\u003e \u003c/p\u003e\n\u003cp\u003eFew studies have directly compared the real-world costs of GnRH-ant versus PPOS in achieving live births. Some evidence suggests that PPOS may be less costly per ovarian stimulation cycle in donor and fertility preservation cases.\u003csup\u003e16-20\u003c/sup\u003e A simulation study estimated that the cost per live birth with one fresh embryo transfer following GnRH-ant was significantly lower than that of one FET following PPOS, by approximately $4,447–12,797, with the cost advantage persisting when accounting for subsequent FET cycles.\u003csup\u003e15\u003c/sup\u003e In our study, CLBR in the GnRH-ant protocol was 1.98% higher than in the PPOS group, with a cost difference of $40.53, resulting in an ICER of $2,067 per additional live birth. Furthermore, the probability of GnRH-ant being more cost-effective exceeded 50% at WTP thresholds of US$5,000 and above. As of this manuscript's completion, no published cost-effectiveness analyses directly comparing the two COS protocols exists, regardless of the clinical endpoint used. A systematic review of economic evaluations of ART in high-income countries noted that while COS was the most frequently analyzed ART intervention, only one study specifically compared GnRH-ant and PPOS.\u003csup\u003e43\u003c/sup\u003e \u003c/p\u003e\n\u003cp\u003eHowever, global fertility treatment costs vary widely, with the cost per live birth after one fresh ET ranging from $4,245 in South Korea to $12,314 in Australia.\u003csup\u003e44\u003c/sup\u003e While no consensus exists on WTP thresholds for fertility treatments, ICER remains the most commonly used cost-effectiveness measure.\u003csup\u003e45\u003c/sup\u003e Published WTP thresholds range from €2,945 for a 5% increase in live birth rates in the UK to €98,533 for one guaranteed live birth via ART in the US.\u003csup\u003e45\u003c/sup\u003e Our findings of costs per live birth slightly above $9,000 and per patient around $5,000 for both protocols align with these global estimates. Furthermore, the WTP thresholds used in our analysis not only encompass our ICER estimates but also align with those reported in the literature. Given similar CLBRs and modest cost differences found in our study, clinicians should consider both the economic metrics and clinical outcomes when formulating ART treatment strategies through shared decision-making. \u003c/p\u003e\n\u003cp\u003eThe current study has limitations that warrant discussion. Firstly, its retrospective design potentially introduces selection bias and confounding factors that may influence both efficacy and economic outcomes. The lack of prospective observation and randomization further limits causal interpretation. Additionally, as a single-center study conducted within one country, variations in clinical practice and healthcare costs may affect the generalizability of our findings. Lastly, patient preferences and quality of life, which are critical in treatment decision-making, were not assessed. Future multinational randomized trials addressing patient-centered factors are needed to validate and extend our findings.\u003c/p\u003e\n\n"},{"header":"Conclusion","content":"\u003cp\u003eThis study compared the efficacy of GnRH-ant and PPOS protocols and is a first to evaluate their cost-effectiveness in CLBRs. Both protocols achieved similar pregnancy and live birth rates with comparable medical costs, though GnRH-ant was potentially more cost-effective at higher WTP thresholds. Additionally, GnRH-ant significantly shortened the time from ovarian stimulation to live birth. These findings suggest that GnRH-ant is a clinically and economically viable COS option, particularly for patients prioritizing a shorter time to live birth under a more flexible financial setting.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eant, antagonist (as in GnRH-ant)\u003c/p\u003e\n\u003cp\u003eAMH, anti-M\u0026uuml;llerian hormone\u003c/p\u003e\n\u003cp\u003eART, assisted reproductive technology\u003c/p\u003e\n\u003cp\u003eBMI, body mass index\u003c/p\u003e\n\u003cp\u003eCEAC, cost-effectiveness acceptability curve\u003c/p\u003e\n\u003cp\u003eCLBR\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003ecumulative live birth rate\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCOS, controlled ovarian stimulation\u003c/p\u003e\n\u003cp\u003eET, embryo transfer\u003c/p\u003e\n\u003cp\u003eFET, frozen embryo transfer\u003c/p\u003e\n\u003cp\u003eFSH, follicle-stimulating hormone\u003c/p\u003e\n\u003cp\u003eGnRH-ant, gonadotropin-releasing hormone antagonist\u003c/p\u003e\n\u003cp\u003eICER, incremental cost-effectiveness ratio\u003c/p\u003e\n\u003cp\u003eICSI, intracytoplasmic sperm injection\u003c/p\u003e\n\u003cp\u003eIVF, in vitro fertilization\u003c/p\u003e\n\u003cp\u003eLB, live birth\u003c/p\u003e\n\u003cp\u003eLH, luteinizing hormone\u003c/p\u003e\n\u003cp\u003eN/A, not applicable\u003c/p\u003e\n\u003cp\u003eOHSS, ovarian hyperstimulation syndrome\u003c/p\u003e\n\u003cp\u003eOPU, ovum pick-up\u003c/p\u003e\n\u003cp\u003eOS, ovarian stimulation\u003c/p\u003e\n\u003cp\u003ePPOS, progestin-primed ovarian stimulation\u003c/p\u003e\n\u003cp\u003ePSA, probabilistic sensitivity analysis\u003c/p\u003e\n\u003cp\u003eUSD, United States dollar\u003c/p\u003e\n\u003cp\u003eWTP, willingness-to-pay\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJui-Chun Chang: Investigation, Formal analysis, Writing - Original Draft, Writing - Review \u0026amp; Editing, Methodology, Project administration, Resources, Validation, Visualization\u003c/p\u003e\n\u003cp\u003eYu-Chiao Yi: Investigation, Writing - Original Draft, Project administration, Resources\u003c/p\u003e\n\u003cp\u003eHwa-Fen Guu: Investigation, Writing - Original Draft, Project administration, Resources\u003c/p\u003e\n\u003cp\u003eYa-Fang Chen: Investigation, Formal analysis, Writing - Original Draft, Methodology, Project administration, Resources, Visualization\u003c/p\u003e\n\u003cp\u003eLi-Yu Chen: Investigation, Writing - Original Draft, Project administration, Resources\u003c/p\u003e\n\u003cp\u003eHsiao-Fan Kung: Investigation, Writing - Original Draft, Project administration, Resources\u003c/p\u003e\n\u003cp\u003eYu-Mei Chang: Formal analysis, Writing - Original Draft, Writing - Review \u0026amp; Editing, Methodology, Software, Visualization\u003c/p\u003e\n\u003cp\u003eMing-Jer Chen: Conceptualization, Investigation, Writing - Original Draft, Writing - Review \u0026amp; Editing, Methodology, Project administration, Resources, Supervision, Validation, Visualization\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was reviewed and approved by the Institutional Review Board of Taichung Veterans General Hospital (IRB: CE24607A), which waived the requirement for informed consent due to the retrospective nature of the study. This study was performed in adherence with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganization, W. 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A prospective study with repeated ovarian stimulation cycles. \u003cem\u003eHuman reproduction\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 1098-1104. https://doi.org/10.1093/humrep/deae047 (2024).\u003c/li\u003e\n\u003cli\u003eMeyer, L.\u003cem\u003e et al.\u003c/em\u003e Risk factors for a suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles. \u003cem\u003eFertility and sterility\u003c/em\u003e \u003cstrong\u003e104\u003c/strong\u003e, 637-642. https://doi.org/10.1016/j.fertnstert.2015.06.011 (2015).\u003c/li\u003e\n\u003cli\u003eBosch, E.\u003cem\u003e et al.\u003c/em\u003e Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists--a randomized study. \u003cem\u003eHuman reproduction\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 2346-2351. https://doi.org/10.1093/humrep/den220 (2008).\u003c/li\u003e\n\u003cli\u003eXie, Y.\u003cem\u003e et al.\u003c/em\u003e A delayed ovulation of progestin-primed ovarian stimulation (PPOS) by downregulating the LHCGR/PGR pathway. \u003cem\u003eiScience\u003c/em\u003e \u003cstrong\u003e26\u003c/strong\u003e, 107357. https://doi.org/10.1016/j.isci.2023.107357 (2023).\u003c/li\u003e\n\u003cli\u003eAta, B.\u003cem\u003e et al.\u003c/em\u003e Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles? \u003cem\u003eReproductive biomedicine online\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, 103626. https://doi.org/10.1016/j.rbmo.2023.103626 (2024).\u003c/li\u003e\n\u003cli\u003eAta, B. \u0026amp; Kalafat, E. Progestin-primed ovarian stimulation: for whom, when and how? \u003cem\u003eReproductive biomedicine online\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, 103639. https://doi.org/10.1016/j.rbmo.2023.103639 (2024).\u003c/li\u003e\n\u003cli\u003eOlive, E.\u003cem\u003e et al.\u003c/em\u003e Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review. \u003cem\u003eHuman reproduction\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 981-991. https://doi.org/10.1093/humrep/deae039 (2024).\u003c/li\u003e\n\u003cli\u003eMatorras, R.\u003cem\u003e et al.\u003c/em\u003e Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective. \u003cem\u003eBest practice \u0026amp; research. Clinical obstetrics \u0026amp; gynaecology\u003c/em\u003e \u003cstrong\u003e89\u003c/strong\u003e, 102349. https://doi.org/10.1016/j.bpobgyn.2023.102349 (2023).\u003c/li\u003e\n\u003cli\u003eFenwick, E.\u003cem\u003e et al.\u003c/em\u003e The value of treatment for infertility: A systematic literature review of willingness-to-pay thresholds and approaches for determining the cost effectiveness of fertility therapies. \u003cem\u003eBest practice \u0026amp; research. Clinical obstetrics \u0026amp; gynaecology\u003c/em\u003e \u003cstrong\u003e89\u003c/strong\u003e, 102340. https://doi.org/10.1016/j.bpobgyn.2023.102340 (2023).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Progestin-primed ovarian stimulation, gonadotrophin-releasing hormone antagonist, cost-effectiveness, cumulative live birth rate, controlled ovarian stimulation, assisted reproductive technology","lastPublishedDoi":"10.21203/rs.3.rs-6803353/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6803353/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eObjective: \u003c/em\u003eThis study compared the cumulative live birth rates (CLBRs) and cost-effectiveness of the GnRH antagonist (GnRH-ant) versus progestin-primed ovarian stimulation (PPOS) protocols in controlled ovarian stimulation (COS).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMethods: \u003c/em\u003eIn this retrospective study, women who underwent COS with GnRH-ant or PPOS at Taichung Veterans General Hospital, from 2018 through 2022, were analyzed. After applying exclusion criteria, eligible participants were matched in a 3:1 ratio using propensity score matching based on age and anti-Müllerian hormone levels. \u0026nbsp;Clinical outcomes and cost-effectiveness were evaluated, with incremental cost-effectiveness ratio (ICER) and probabilistic sensitivity analysis (PSA) conducted based on various willingness-to-pay (WTP) thresholds.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults: \u003c/em\u003eA total of 225 patients who underwent COS with GnRH-ant and 85 patients with PPOS were included. GnRH-ant required significantly lower gonadotropin doses, a shorter stimulation duration, and yielded a higher MII oocyte rate. Pregnancy and live birth rates after the first embryo transfer were similar between the two protocols, while the GnRH-ant group had a numerically higher CLBR (56.08% vs 54.12%) and a significantly shorter time from stimulation to live birth (351.28 ± 138.59 vs. 394.42 ± 105.90 days, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) per aspirated cycle compared to PPOS. Medical costs by procedure and in total were comparable, with an ICER of $2,067.14 per additional live birth for GnRH-ant. PSA indicated a 40% probability of cost-effectiveness at a $2,000 WTP threshold, with the probability increasing to 58.0% at $10,000 and 61.3% at $30,000.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusion: \u003c/em\u003eBoth protocols yielded similar pregnancy and live birth outcomes, with GnRH-ant being a cost-effective option under more lenient WTP settings. Moreover, GnRH-ant was associated with a shorter time from stimulation to live birth, potentially benefiting women who seek to conceive sooner.\u003c/p\u003e","manuscriptTitle":"Comparison of Cumulative Live Birth Rates and Cost-Effectiveness Between GnRH Antagonist and Progestin-Primed Ovarian Stimulation Protocols Running title: Cost-effectiveness of GnRH-ant vs PPOS","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-10 18:13:11","doi":"10.21203/rs.3.rs-6803353/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"873d7e34-dd3d-4ba2-8b0f-d3bbf67ed1eb","owner":[],"postedDate":"June 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":49566937,"name":"Health sciences/Endocrinology"},{"id":49566938,"name":"Health sciences/Health care"},{"id":49566939,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-07-22T04:23:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-10 18:13:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6803353","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6803353","identity":"rs-6803353","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}