The impact of changes in LH levels in flexible antagonist protocols on the clinical outcomes of fresh IVF/ICSI cycles in populations of POSEIDON groups 1 and 2: a retrospective cohort study

The impact of changes in LH levels in flexible antagonist protocols on the clinical outcomes of fresh IVF/ICSI cycles in populations of POSEIDON groups 1 and 2: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The impact of changes in LH levels in flexible antagonist protocols on the clinical outcomes of fresh IVF/ICSI cycles in populations of POSEIDON groups 1 and 2: a retrospective cohort study Yuan Zhou, Yanying Lin, Lili Chen, Lisheng Huang, Yizhen Yang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4405209/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To investigate the impact of changes in luteinizing hormone (LH) levels during ovulation induction using flexible gonadotropin-releasing hormone antagonist (GnRH-A) regimens in POSEIDON groups 1 and 2 on the clinical outcomes of fresh in-vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) cycles. Method: A retrospective analysis was conducted on the clinical data of females in POSEIDON groups 1 and 2 who underwent the IVF/ICSI used flexible GnRH-A regimen at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital from January 2017 to December 2022. According to the values of change in LH [(LH level on the trigger day − baseline LH)/baseline LH], the study subjects were divided into 7 groups. The general information, laboratory indicators, and clinical outcomes of each group were compared. Results: Significant difference was observed in terms of the number of retrieved eggs, mature eggs, fertilization number (2PN number), cleavage, and excellent embryos among all groups (all P values < 0.05). The number of eggs retrieved in group A was significantly lower than that in groups E, F, and G (P = 0.042, 0.011, and 0.000, respectively). The number of eggs retrieved in group B was significantly lower than that in group G (P = 0.013). The number of mature eggs in group A was significantly lower than that in groups E, F, and G (P = 0.017, 0.023, and 0.000, respectively). Group B exhibited significantly lower number of mature eggs than group G (P = 0.005). The 2PN number in group A was significantly lower than that in groups E, F, and G (P = 0.033, 0.016, and 0.000, respectively). The cleavage count of group A was significantly lower than that of groups E and G (P = 0.035 and 0.000, respectively). Conclusion: The use of a flexible GnRH-A regimen to induce ovulation in the POSEIDON groups 1 and 2 can lead to better clinical outcomes. This involves adjusting the dosage of gonadotropin(Gn) and antagonists during the controlled ovarian stimulation(COS) process, to control the LH level on trigger day and allow it to decrease within the range of 0%–100% from baseline (with optimal range being ≥ −100% to −50%). POSEIDON groups 1 and 2 flexible GnRH-A regimen changes in LH levels Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Introduction During the decades of flourishing advances in assisted reproductive technology, many ovulation induction regimens have been developed. However, currently, the most commonly used and prevalent regimens in clinical practice are the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-A regimens. Compared with the GnRH-a regimen, the GnRH-A regimen exhibits advantages such as short treatment time, low Gn dosage, flexible medication, rapid inhibition of LH peak, and low incidence of ovarian hyper-stimulation syndrome (OHSS). It is the most commonly used controlled ovulation induction regimen for high ovarian response (HOR) and poor ovarian response (POR). Although experts from China have reached a consensus on the standardized application of GnRH-A regimens[ 1 ], clinicians still need to continuously explore and improve the control and optimization of key nodes in the use of GnRH-A regimens in practice. In the process of antagonist therapy in COS, reasonably controlling the serum LH value is challenging. Early onset and sudden LH peaks can lead to premature luteinization of follicles, affecting the rate of egg retrieval and endometrial receptivity. However, LH itself is a substrate for estrogen synthesis and is essential in the middle and late stages of follicular development and final maturation. Excessive suppression of LH may lead to a high proportion of immature eggs and insufficient luteal function [ 2 ]. Recent studies have reported that baseline LH and LH fluctuations during the antagonist COS process do not affect the clinical outcomes of patients. Even if LH temporarily increases, timely addition of antagonists and rapid decrease in LH levels will not have adverse effects on the clinical outcomes of IVF [ 3 – 5 ]. However, previous studies have mostly focused on the HOR or entire population, and only few reports have focused on the regulation of antagonist regimens in the POR population. In clinical practice, it is difficult to precisely regulate the level of LH in individuals. Therefore, in this study, we focused on elucidating a more convenient observation method to control the nodes and optimize the clinical outcomes of patients. Previously, the Bologna criteria were often used to define POR. In 2016, the POSEIDON group shifted its focus from “low responsiveness” to “low prognosis” and proposed a POSEIDON stratification approach, dividing the POR population into four subgroups. Among them, groups 1 and 2 had normal ovarian reserve function (AFC ≥ 5 and AMH ≥ 1.2 ng/mL); however, unexpected POR or suboptimal response occurred [ 6 ]. Regulating the COS regimen in this population can achieve the same live birth rate as the population with normal ovarian response [ 7 ]. In this study, we retrospectively analyzed the population of POSEIDON groups 1 and 2 who underwent IVF/ICSI with flexible antagonist regimen. Furthermore, the correlation between changes in LH level during the COS process and clinical outcomes of fresh cycle were investigated. This study can help clinicians to assess the COS process with antagonist protocol, optimize the ovulation promotion plan, and improve clinical outcomes of patients. Materials and Methods 1.1 Research subjects and grouping Retrospective analysis was performed using clinical data of POSEIDON groups 1 and 2 treated with the flexible IVF/ICSI regimen of GnRH-A at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital from January 2017 to December 2022. The inclusion criteria were as follows: 1) POSEIDON group 1 population [age < 35 years, normal ovarian reserve function (AFC ≥ 5 and AMH ≥ 1.2 ng/mL)] with unexpected ovarian low response or suboptimal response (number of retrieved eggs ≤ 9) or POSEIDON group 2 population [age ≥ 35 years and normal ovarian reserve function (AFC ≥ 5 and AMH ≥ 1.2 ng/mL)] with unexpected ovarian low response or suboptimal response (number of retrieved eggs ≤ 9); 2) Flexible COS using antagonists. Exclusion criteria: 1) polycystic ovary syndrome; 2) multiple uterine fibroids (or single fibroid ≥ 5 cm); 3) history of intrauterine adhesions; 4) ovarian tumors; 5) uterine adenomyosis; 6) endometriosis uterine malformation; and 7) chromosomal abnormalities in either spouse causing recurrent implantation failure (RIF) or recurrent miscarriage (RSA). According to the value of LH change [(LH level on the trigger day − baseline LH)/baseline LH], the study subjects were divided into 7 groups: groups A, B, C, D, E, F, and G with the value of LH change ≥ 100%, ≥ 50% to < 100%, ≥ 25% to < 50%, ≥ 0% to < 25%, ≥ −25–0%, ≥ −50% to − 25%, and ≥ − 100% to − 50%, respectively. 1.2 Flexible GnRH-A regimens Starting from the days 2–5 of menstruation, Gn [Recombinant Human Follitropin Alfa Solution for Injection (Merck, Germany; Procon, Merck, USA) or Urofollitropin for Injection (Zhuhai Lizhu Pharmaceutical Company)] was administered with an initial dose of 100–600 IU after considering the patient’s age, body mass index(BMI), AMH, basal follicle stimulating hormone (FSH), and antral follicle count (AFC) levels. After Gn activation, serum FSH, LH, estradiol (E2), and progesterone (Prog) levels were checked every 3–5 days. Antagonist was added when the diameter of the dominant follicle reached 14 mm or approximately 15 mm or when the diameter of the dominant follicle was > 12 mm and E2 > 300 ng/L (1 ng/L = 3.672 pmol/L). The dosage was adjusted till trigger day based on the follicle size and hormone levels. When the diameter of 3 dominant follicles was ≥ 17 mm, that of 2 dominant follicles was ≥ 18 mm, or that of 1 dominant follicle was ≥ 20 mm, trigger was induced by administering recombinant human chorionic gonadotropin(hCG) (Aize, Merck, Switzerland) 250 µg or hCG (Zhuhai Lizhu Group Lizhu Pharmaceutical Factory) 6000–10,000 IU. Egg retrieval was performed after 36 h. 1.3 Laboratory indicators The cleavage stage embryos and blastocysts were evaluated based on the consensus of Chinese experts on morphological evaluation of human cleavage-stage embryos and blastocysts [ 8 ]. The laboratory indicators included number of retrieved eggs, rate of egg retrieval, number of fertilization (2PN), fertilization rate, number of cleavage, cleavage rate, number of excellent embryos, rate of excellent embryos, number of blastocysts, and rate of blastocyst formation. The relevant indicators were assessed via referring to the consensus of experts on quality control of clinical key indicators of assisted reproductive technology, which included egg retrieval rate = (the number of eggs retrieved/number of follicles penetrated) × 100% fertilization rate (2PN fertilization rate) = (number of double pronuclear fertilizations/number of retrieved eggs) × 100% cleavage rate = (number of cleavage/number of double pronuclear fertilization) × 100% excellent embryo rate = (number of excellent embryos/number of cleavage) × 100% blastocyst formation rate = (number of blastocysts/number of blastocyst cultures) × 100%. 1.4 Clinical indicators Clinical indicators included fresh cycle clinical pregnancy rate and live birth rate, which were calculated as follows: clinical pregnancy rate (per fresh transplant cycle) = (number of clinical pregnancy cycles/number of fresh transplant cycles) × 100% live birth rate (per fresh transfer cycle) = (number of live births/number of fresh embryo transfer cycles) × 100%. 1.5 Statistical analysis SPSS23.0 was used for statistical analysis. Quantitative data that conform to normal distribution were expressed as mean ± standard deviation. Further, homogeneity of variance testing was performed. Data with homogeneity of variance were analyzed using two independent sample t-tests. Non-normally distributed data were represented by median and interquartile intervals. Kruskal Wallis H-test (KW test) was used for intergroup comparisons, and Bonferroni method was used for pairwise comparisons between groups. Data were subjected to χ2 test. P < 0.05 was considered significant. Result Data from 733 eligible patients were included, with 25, 33, 31, 53, 78, 148, and 365 cases in groups A, B, C, D, E, F, and G, respectively. Moreover, there were 467 fresh transplant cycles, 173 clinical pregnancies, and 130 live births. 2.1 Comparison of general information of patients in each group No significant differences were observed in terms of the types of infertility, years of infertility, total Gn, baseline FSH, and Prog level and endometrial thickness on the trigger day among the groups (P values ≥ 0.05). The differences were significant among groups in terms of age, BMI, time to antagonist addition, initial Gn dose, Gn days, baseline LH, baseline AMH, LH and E2 levels on the trigger day (all P values < 0.05; Table 1 ). Table 1 Comparison of general information A B C D E F G P Age 34.24 ± 5.60 35.40 ± 5.53 33.10 ± 5.22 36.00(10.00) 36.00(8.00) 34.00(7.00) 33.00(6.00) 0.000 BMI 23.29 ± 2.75 21.72(3.31) 23.08 ± 3.14 22.03(3.00) 21.77(3.79) 22.29(4.05) 21.23(4.03) 0.002 primary infertility 11/25 10/33 15/31 19/53 27/78 60/148 151/365 0.237 secondary infertility 14/25 23/33 16/31 34/53 51/78 88/148 214/365 years of infertility 3.00(5.00) 3.00(4.50) 2.00(3.00) 3.00(5.00) 3.00(3.00) 3.00(3.75) 3.00(3.00) 0.435 time to antagonist addition 7.00(2.50) 6.00(1.00) 6.00(2.00) 7.00(2.00) 6.00(3.00) 6.00(2.00) 7.00(1.00) 0.024 initial Gn dose 225.00(25.00) 225.00(75.00) 225.00(25.00) 225.00(0.00) 225.00(0.00) 225.00(25.00) 225.00(50.00) 0.001 total Gn 2555.00 ± 767.20 2400.00(1387.50) 2125.00(600.00) 2400.00(1012.50) 2250.00(743.75) 2250.00(900.00) 2250.00(875.00) 0.158 Gn days 10.56 ± 2.12 9.00(3.00) 10.00(2.00) 10.00(2.00) 10.00(2.00) 10.00(2.00) 10.00(2.00) 0.008 baseline FSH 6.17 ± 2.35 6.42(3.50) 6.70 ± 2.12 6.67(2.87) 7.03(2.55) 6.54(2.52) 6.77(2.43) 0.290 baseline LH 1.74(1.12) 2.20(1.60) 2.48 ± 1.43 2.30(1.70) 2.60(1.42) 3.00(1.74) 3.70(1.90) 0.000 AMH 1.86(1.21) 1.72(0.95) 2.09(1.57) 1.87(1.89) 1.96(1.72) 2.23(1.50) 2.47(2.16) 0.000 LH on the trigger day 4.60(4.45) 3.69(2.55) 3.41 ± 1.96 2.30(1.95) 2.22(1.44) 1.90(1.10) 1.00(0.70) 0.000 E2 on the trigger day 1045.00(1551.50) 1227.00(1412.00) 1454.00(1248.00) 1535.00(994.50) 1361.00(1260.00) 1482.50(1559.25) 1912.00(1599.00) 0.000 Prog on the trigger day 0.50(0.59) 0.60(0.46) 0.70(0.57) 0.56(0.41) 0.60(0.40) 0.54(0.50) 0.60(0.60) 0.734 endometrial thickness on the trigger day 11.20 ± 2.09 10.71 ± 1.92 10.85 ± 1.84 11.00(1.95) 10.87 ± 1.78 11.00(2.15) 10.80(2.60) 0.817 Note Quantitative data that conform to normal distribution were expressed as mean ± standard deviation.Non-normally distributed data were represented by median and interquartile intervals. BMI: body mass index; Gn: gonadotropin; FSH: follicle stimulating hormone; LH: luteinizing hormone; E2: estradiol Further grouping comparison indicated that in terms of age, only group E patients were significantly older than group G patients (P = 0.000). The other components exhibited no significant differences (all P values ≥ 0.05; Fig. 1 ). In terms of BMI, time for antagonist addition, and Gn days, the differences were not significant among groups (all P values ≥ 0.05; Figs. 2 – 4 ). In terms of initial Gn dose, the median for each group was 225 IU. However, significant difference was observed between groups G and D (P = 0.028), as well as between group G and E (P = 0.036; Fig. 5 ). In terms of baseline LH, groups F and G exhibited significantly higher baseline LH values than other groups (all P values < 0.05; Fig. 6 ). In terms of basic AMH, group G exhibited higher level, which was significantly different compared with that in groups B and E (P = 0.003 and 0.036, respectively; Fig. 7 ). In terms of daily LH in hCG, significant differences were observed among the groups (all P values < 0.05; Fig. 8 ). In terms of E2 on hCG day, only group E exhibited significantly lower value than group G (P = 0.042; Fig. 9 ). 2.2 Comparison of laboratory indicators and clinical outcomes among various groups No significant difference (P ≥ 0.05) was observed among the groups in terms of egg retrieval rate, fertilization rate, cleavage rate, excellent embryo rate, blastocyst number, and blastocyst formation rate. However, significant difference (P value < 0.05) was observed in terms of number of retrieved eggs, mature egg number, fertilization number (2PN number), number of cleavage, and excellent embryo number (P < 0.05; Table 2 ). In addition, although no significant difference was observed among the groups in terms of the number of blastocysts, the groups with reducing in LH level (D, E, F, and G) generally had higher blastocyst numbers than those with increasing LH level (A, B, and C). Table 2 Comparison of laboratory indicators A B C D E F G P the number of eggs retrieved 3.80 ± 2.81 4.76 ± 2.56 5.65 ± 2.14 5.58 ± 2.37 5.82 ± 2.24 5.85 ± 2.44 6.29 ± 2.14 0.000 egg retrieval rate (%) 75.35 ± 33.70 90.82 ± 15.87 88.23 ± 18.27 88.79 ± 18.62 89.64 ± 16.14 89.36 ± 18.41 89.46 ± 16.39 0.575 mature egg number 3.44 ± 2.57 4.42 ± 2.41 4.84 ± 2.07 4.94 ± 2.40 5.44 ± 2.32 5.34 ± 2.39 5.98 ± 2.18 0.00 number of double pronuclear fertilizations (2PN) 2.84 ± 2.11 3.88 ± 2.37 4.19 ± 2.10 4.40 ± 2.28 4.69 ± 2.19 4.47 ± 2.33 5.07 ± 2.17 0.00 fertilization rate (%) 73.95 ± 35.06 83.15 ± 26.95 75.67 ± 25.69 80.19 ± 26.45 82.19 ± 20.64 77༎71 ± 26.05 82.00 ± 21.88 0.565 number of cleavage 2.76 ± 2.07 3.64 ± 2.33 3.97 ± 2.12 4.13 ± 2.43 4.45 ± 2.11 4.28 ± 2.36 4.79 ± 2.20 0.000 cleavage rate (%) 86.00 ± 33.22 88.08 ± 28.02 91.61 ± 20.38 86.20 ± 27.42 95.23 ± 9.62 91.00 ± 23.88 92.28 ± 18.68 0.907 cleavage rate 1.92 ± 1.66 2.18 ± 1.79 2.35 ± 1.84 2.70 ± 2.02 2.97 ± 1.94 2.75 ± 1.91 2.94 ± 1.91 0.027 excellent embryo rate 61.22 ± 37.73 54.61 ± 37.85 56.68 ± 32.86 63.84 ± 33.19 64.03 ± 32.17 59.31 ± 32.10 59.82 ± 30.06 0.635 number of blastocysts 0.52 ± 0.96 0.52 ± 0.80 0.77 ± 1.36 1.04 ± 1.29 0.91 ± 1.05 1.01 ± 1.30 1.05 ± 1.34 0.082 blastocyst formation rate 25.40 ± 42.38 26.77 ± 39.73 27.42 ± 41.57 37.86 ± 42.40 33.17 ± 36.45 38.50 ± 42.96 39.14 ± 41.44 0.246 Note Quantitative data that conform to normal distribution were expressed as mean ± standard deviation. In terms of the number of eggs retrieved, group A exhibited significantly lower number than groups E, F, and G (P = 0.042, 0.011, and 0.0000, respectively) and group B exhibited significantly lower number than group G (P = 0.013; Fig. 10 ). In terms of the number of mature eggs, group A exhibited significantly lower number than groups E, F, and G (P = 0.023, 0.017, and 0.0000, respectively) and group B exhibited significantly lower number than group G (P = 0.005; Fig. 11 ). In terms of fertilization number (2PN number), group A exhibited significantly lower number than groups E, F, and G (P = 0.016, 0.033, and 0.000, respectively; Fig. 12 ). In terms of cleavage count, group A exhibited significantly lower value than groups E and G (P = 0.035 and 0.0000, respectively; Fig. 13 ). No significant difference was observed in terms of clinical pregnancy rate and live birth rate among the groups (P ≥ 0. 05; Table 3 ). Table 3 Comparison of clinical outcomes 组别 ≥ 100% ≥ 50 ~ < 100% ≥ 25%~<50% ≥ 0 ~ < 25% ≥-25%~0 ≥-50%~-25% ≥-100%~-50% χ2 P A B C D E F G clinical pregnancy rate 4/13 7/25 6/19 13/35 17/55 35/89 91/231 2.973 0.151 live birth rate 2/4 6/7 6/6 10/13 10/17 29/35 67/91 5.036 0.284 Note clinical pregnancy rate = number of clinical pregnancy cycles/number of fresh transplant cycles;live birth rate = number of live births/number of fresh embryo transfer cycles. Discussion LH is crucial for the development of follicles. In the middle and late stages of follicular development, granulosa cells also have LH receptors that can promote follicle maturation and induce ovulation. Particularly for patients with POR, adding LH appropriately can achieve better clinical outcomes [ 9 – 11 ]. Previous studies have proposed the concept of “LH treatment window,” believing that LH levels above or below the threshold level will lead to insufficient E2 levels, thereby affecting follicular development [ 12 ]. Some studies suggested that the rate and direction of LH changes determine follicular development, and basline LH values and LH fluctuations before the addition of antagonists do not affect patient outcomes [ 3 , 13 – 15 ]. However, Zhang believed that although the application of antagonists can inhibit LH surge, it will have adverse effects on embryonic development and pregnancy outcomes in fresh transfer cycles [ 16 ]. Therefore, the control of LH levels during the process of ovulation promotion is debatable. The key to the flexible use of antagonists lies in how to regulate LH levels during the COS process through timely and appropriate addition of antagonists, thereby improving patient egg retrieval, embryo retrieval, and clinical outcomes [ 1 ]. In clinical practice, medication dosage is generally adjusted every few days based on the patient’s follicular development and hormonal changes. It is difficult to accurately control the LH changes at each time node, and the global view of LH fluctuations can only be reflected on the trigger day. If unexpected LH fluctuations occur, timely remedies may not be possible. Therefore, it is necessary to explore a more convenient and intuitive way to describe LH fluctuations and guide clinicians to regulate serum LH values based on outcomes. In this study, the patients were divided based on overall changes in LH during the COS process (LH level on the trigger day − baseline LH), and the laboratory and clinical outcomes of each group were compared. Compared with the patients with an increase in LH levels by ≥ 100%, those with a decrease in LH levels exhibited more number of retrieved eggs, mature eggs, 2PN, cleavage, and blastocysts. Among them, group G exhibited superior performance (LH change ≥ − 100% to − 50%); however, no significant difference was observed in terms of the number of superior embryos, clinical pregnancy, and live birth outcomes among the groups. This is similar to the research findings of Wang and Ji, who believed that LH levels on trigger day are negatively correlated with the number of retrieved eggs but have no significant impact on the clinical pregnancy outcomes of patients [ 17 – 18 ]. This suggested that during the COS process, maintaining the LH level within the range of 0–100% lower than the baseline (with ≥ − 100% to − 50% being optimal) can lead to better egg and embryo outcomes. Patients with low ovarian response have poorer pregnancy outcomes via assisted reproductive technology (ART) and higher treatment costs compared with those with normal ovarian response. However, if the COS regimen can be reasonably grasped, they can achieve the same clinical outcomes as the normal population [ 8 ]. This study targeted the population of POSEIDON groups 1 and 2, as their ovarian reserve function is still acceptable but they exhibit unexpected low responses resulting in suboptimal egg retrieval. Previous studies have suggested that this may be related to mutations in Gn receptor genes or single nucleotide polymorphisms (SNPs) [ 19 – 20 ]. Some scholars also believe that this may be related to the low initial dose of Gn [ 7 , 21 ]. In the early stages of COS, the application of exogenous Gn can stimulate the secretion of gonadotropin large inhibitory factor (GnSAF) in the ovaries. Studies have reported that during the ART cycle, GnSAF is secreted by follicles smaller than 11 mm; its biological activity is the highest in the early and middle stages of follicular development, gradually decreasing in the late stage. It can reduce the pituitary gland’s responsiveness to Gn by inhibiting the positive feedback effect of estrogen, thereby regulating LH secretion. Therefore, for POR, a sufficient amount of Gn activation can ensure the secretion of GnSAF and prevent premature LH peak [ 22 – 23 ]. In this study, the median initial Gn dose for each group was 225 IU; however, the difference was significant as revealed by K-W test. Specifically, group G exhibited a lower initial Gn dose than groups D and E (the average initial Gn dose for groups D, E, and G was 230.90 (221.18–240.61), 233.17 (221.88–244.46), and 210.79 (205.75–215.83), respectively]. Due to the minimum fine-tuning unit of Gn being 12.5–25 IU, the precise control range is limited in practical operation. Therefore, we suggest that the Gn activation amount can be based on 225 IU, combined with patient age, BMI, basic AMH, AFC, and comprehensive control of previous COS process. In summary, our study suggested that using a flexible antagonist regimen to induce ovulation in the POSEIDON groups 1 and 2 can lead to better clinical outcomes by adjusting the dosage of Gn and antagonists during the COS process, to control the LH level on trigger day and allow it to decrease within the range of 0–100% from baseline (with ≥ − 100% to − 50% being optimal). The limitations of this study are detailed grouping and small sample size in some groups. Moreover, this was a single-center retrospective study. In future, we will conduct multicenter studies, increase sample size, and explore the key node control of flexible antagonist strategies in detail. Declarations Acknowledgements We would like to express our thanks to Bullet Edits Limited for their assistance in the linguistic editing and proofreading of this manuscript. Author contributions ZBH contributed to the research design. ZY collected the patient data. ZY, LYY, CLL, HLS and YYZ analyzed and interpreted the patient data. ZY and ZBH were involved in the manuscript development. All authors have read and approved the final manuscript. Funding This study was supported by grants from the Natural Science Foundation of Fujian Province (No. 2023J011229). Data Availability The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request. Ethics approval and consent to participate This study was performed in accordance with the Declaration of Helsinki and was approved by the Medical Research Ethics Committee of Fujian Maternity and Child Health Hospital (Ethics approval number: 2024KY057). All patients are exempt from informed consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References Expert Consensus Compilation Group of Reproductive Medicine Committee of China Medical Women's Association. Expert consensus on standardized application of antagonist protocol in assisted reproductive technology[J]. Chin J Reprod Contracep, 2022 , 42 (2): 109 -116. DOI: 10 .3760/ cma.j.cn101441-20211108-00495. Wang M, Xi Q, Yang Q, et al.The relationship between a novel evaluation parameter of premature luteinization and IVF outcomes[J/OL]. Reprod Biomed Online, 2021 , 42(2): 323-331. DOI: 10.1016/j.rbmo.2020.20.009. Liu Z , Wang K H .Effect of basal luteinizing hormone (bLH) level on in vitro fertilization/intra-cytoplasmic injections (IVF/ICSI) outcomes in polycystic ovarian syndrome (PCOS) patients[J].BMC Pregnancy and Childbirth, 2023, 23(1).DOI:10.1186/s12884-023-05944-4. Huang JD, Yang RX, Dong XZ, et al. The Effect of Early Elevation of LH in GnRH Antagonist Protocol on Clinical Outcomes of IVF/ICSI Fresh Embryo Transfer: A Propensity Score Matching Study [J]. Chinese Journal of Reproduction and Contraception, 2023, 43(12): 1244-1248. DOI: 10.3760/cma.j.cn101441-20221116-00511. Xiao S, Mo ML, Liu S, et al. Impact of early onset LH elevation in antagonist regimens on clinical outcomes of IVF-ET in patients with polycystic ovary syndrome[J]. J Repord Med, 2022, 31(1): 6-12. DOI: 10.3969/j.issn.10043845.2022.01.002. Alviggi C , Andersen C Y , Buehler K ,et al. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept[J].Fertility & Sterility, 2016:1452-1453.DOI:10.1016/j.fertnstert.2016.02.005. Parimala C , Belavendra A , Mangalaraj A M ,et al. POSEIDON classification and the proposed treatment options for groups 1 and 2: time to revisit? A retrospective analysis of 1425 ART cycles[J].Human Reproduction Open(1):1[2024-02-06].DOI:10.1093/hropen/hoaa070. Chinese Association of Reproductive Medicine. Expert consensus on human embryo morphological assessment: cleavage-stage embryos and blastocysts grading criteria[J]. Chin J Reprod Contracep, 2022 , 42 (12): 1218 -1225. DOI: 10.3760/cma.j.cn101441-20220619-00266. Conforti A , Esteves S C , Di Rella F ,et al.The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: A systematic review and meta-analysis[J].Reproductive Biology and Endocrinology, 2019, 17(1).DOI:10.1186/s12958-019-0460-4. Wang L, Wang J, Gao Y, et al. Effects of different exogenous LH activity drugs on pregnancy outcomes in patients with suboptimal ovarian response: a retrospective cohort study,Chinese Journal of Reproduction and Contraception.2023,43(08)：769-776.DOI:10.3760/cma.j.cn101441-20220406-00144. Fischer R, Nakano FY, Roque M, et al. A quality management approach to controlled ovarian stimulation in assisted reproductive technology: the "Fischer protocol"[J]. Panminerva Med, 2019, 61(1): 11-23. DOI: 10.23736/ S0031-0808.18.03549-8. Shoham Z .The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation[J].Fertility and Sterility, 2002.DOI:10.1016/S0015-0282(02)03157-6. Orvieto R , Venetis C A , Fatemi H M ,et al.Optimising Follicular Development, Pituitary Suppression, Triggering and Luteal Phase Support During Assisted Reproductive Technology: A Delphi Consensus[J].Frontiers in endocrinology, 2021, 12:675670.DOI:10.3389/fendo.2021.675670. Huirne J A F , Van L A C D , Roel S ,et al.Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy[J].Human Reproduction(2):359-67[2024-02-08].DOI:10.1093/humrep/deh601. Zhou J S , Chen J H , Tang F F ,et al.The effect of luteinizing hormone changes in GnRH antagonist protocol on the outcome of controlled ovarian hyperstimulation and embryo transfer[J].BMC Pregnancy and Childbirth, 2023, 23(1).DOI:10.1186/s12884-023-05916-8. Zhang D , Zhang D , Sun Z ,et al.The effect of a transient premature luteinizing hormone surge without elevated serum progesterone on invitro fertilization outcomes in a gonadotropin-releasing hormone antagonist flexible protocol[J].Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2019:1-4.DOI:10.1080/09513590.2019.1683730. Wang AC, Wang Y, Wu FX, et al. Assessing predictors for the success of GnRH antagonist protocol in reproductive women in IVF/ICSI - in fresh cycles. Biomed Rep. 2017;7(5):482–6. DOI:10.3892/br.2017.984. Ji Hui C, Meng-xi Z, Chun, et al. Effect of LH level on pregnancy outcome of IVF during controlled ovarian hyperstimulation with antagonist protocol. J Reprod Med. 2017;26(10):972–7. Alviggi C，Conforti A，Santi D，et a1．Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation：a systematic review and meta analysis[J]．Hum Reprod Update，2018，24：599—614．DOI：10.1093/humupd/dmy019. König TE, van der Lee J, Schats R, et al. The relationship between FSH receptor polymorphism status and IVF cycle outcome: a retrospective observational study. Reprod Biomed Online. 2019 Aug;39(2):231-240. DOI: 10.1016/j.rbmo.2019.05.018. Drakopoulos P, Santos-Ribeiro S, Bosch E, et al. The Effect of Dose Adjustments in a Subsequent Cycle of Women With Suboptimal Response Following Conventional Ovarian Stimulation. Front Endocrinol (Lausanne). 2018 Jul 23;9:361. DOI: 10.3389/fendo.2018.00361. Messinis IE, Messini CI, Anifandis G, et al. Gonadotropin Surge-Attenuating factor: a nonsteroidal ovarian hormone Controlling GnRH-Induced LH Secretion in the normal menstrual cycle. Vitam Horm. 2018;107:263–86. DOI:10.1016/bs.vh.2018.01.002. Liu XH, Wu XH. Research progress of gonadotropin inhibitory hormone in female reproduction [J]. Chinese Journal of Birth Health & Heredity, 2018, 26(2):3. DOI: CNKI:SUN:ZYYA.0.2018-02-048. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4405209","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":304020347,"identity":"5e8ad7c7-d4f4-4701-9d84-ae8d4e3d225d","order_by":0,"name":"Yuan Zhou","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Zhou","suffix":""},{"id":304020348,"identity":"641d2bf2-950c-4e43-9684-d861ab1f7850","order_by":1,"name":"Yanying Lin","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yanying","middleName":"","lastName":"Lin","suffix":""},{"id":304020349,"identity":"44c5fc15-4ea6-4b09-bcc7-7d429dbab9bd","order_by":2,"name":"Lili Chen","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Chen","suffix":""},{"id":304020350,"identity":"00563237-977c-43f7-8e6e-a2debb893b7e","order_by":3,"name":"Lisheng Huang","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lisheng","middleName":"","lastName":"Huang","suffix":""},{"id":304020351,"identity":"267a2750-a826-4752-ad8d-aa07fe650703","order_by":4,"name":"Yizhen Yang","email":"","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yizhen","middleName":"","lastName":"Yang","suffix":""},{"id":304020352,"identity":"9b509470-19da-4f1a-aa5d-de03ba5157ee","order_by":5,"name":"Beihong Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYDACCSBmbGDgMQBxPhhI8PAzMx9+QLQWxhkVFnKS7WxpBsRoYQCpYuY5U2FscJ5HQQKfDvnZzcceft1hI2PO3nv4BW+bROLmwzxA/TU20bi0MM45lm4seyaNx7LnXJqFJFDLtsO8Bx4wHEvLbcChhVkix0xasu0wj8GNHDMDQ7AWvgQDxobDOLWwSeR/A2r5D9GSCHJYM4+BBD4tPBI5bJIf2w6AtBg/OHBGwtiAmYAWCYk0M2nGM8k8BmfOmDE2VEjISRwGBnICHr/Iz0h+Jvlzh529wfEe489/DOp4+PsPH37wocYGpxZwEPDA/AUXSsCjHAQYf0C1fiCgcBSMglEwCkYoAACDCVnBfA+IggAAAABJRU5ErkJggg==","orcid":"","institution":"Fujian Maternity and Child Health Hospital, Fujian Medical University","correspondingAuthor":true,"prefix":"","firstName":"Beihong","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2024-05-11 11:39:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4405209/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4405209/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57310182,"identity":"0ebee3eb-c997-4d58-a0f3-eadd5343961d","added_by":"auto","created_at":"2024-05-29 02:51:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46704,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of age\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/1dc081cca45d605e3005a9ba.png"},{"id":57309446,"identity":"b38b0733-f9fb-4ca7-8b7a-ff1e79cd1fec","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":61444,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of BMI\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/875c87bc96ce6a676ea63e56.jpeg"},{"id":57309440,"identity":"4db37ace-6ddc-43e1-a5b9-40ed3707672d","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":62782,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of time to antagonist addition\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/cca906027f53621637ecf730.jpeg"},{"id":57310951,"identity":"2f0f051d-edda-401f-8a7f-83deb1a74f0d","added_by":"auto","created_at":"2024-05-29 02:59:19","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":58386,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Gn days\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/3fd5fc99f0cc3a3c693eb94c.jpeg"},{"id":57310186,"identity":"6ae12056-d4d1-4129-be8f-b8fc8a3e42ca","added_by":"auto","created_at":"2024-05-29 02:51:19","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":63749,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of initial Gn dose\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/788a7df71121854eebc9798f.jpeg"},{"id":57309441,"identity":"1b041d67-57bb-4fc9-afb9-9e7d77820deb","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":84918,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of baseline LH\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/0751cc739e7a50f20ecc5252.jpeg"},{"id":57309442,"identity":"a928faea-09dc-4629-b7e6-90b993abc970","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":59420,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of AMH\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/5c423062b50a13a38d15cf73.jpeg"},{"id":57309449,"identity":"f23e1c8a-8dcd-424c-b834-38876a719856","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"jpeg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":80964,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of LH on the trigger day\u003c/p\u003e","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/e5fa91c3c119aef71bc96a2e.jpeg"},{"id":57309445,"identity":"048e4393-571e-4073-9252-2bd20697a64e","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":43942,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of E2 on the trigger day\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/bd2dfc757ec1a09a1bd45261.png"},{"id":57310183,"identity":"1916f160-9424-4b57-9425-71bf0116d237","added_by":"auto","created_at":"2024-05-29 02:51:19","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":64686,"visible":true,"origin":"","legend":"\u003cp\u003eThe number of eggs retrieved comparison\u003c/p\u003e","description":"","filename":"floatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/5f6cda9e8b4f69af429f114f.png"},{"id":57309451,"identity":"9c41c1a5-580b-4785-979d-f04c4a3bb815","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":52648,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the number of mature eggs\u003c/p\u003e","description":"","filename":"floatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/373c889ec994992c6237efba.png"},{"id":57309450,"identity":"ba42b468-0a14-4ee4-b55a-456c5a780028","added_by":"auto","created_at":"2024-05-29 02:43:19","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":63525,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the number of double pronuclear fertilizations\u003c/p\u003e","description":"","filename":"floatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/c5f77a0ddc9ff4193d2cb024.png"},{"id":57310187,"identity":"3d947065-4490-49ba-b51e-c74f002da4c6","added_by":"auto","created_at":"2024-05-29 02:51:20","extension":"jpeg","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":82365,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the number of cleavage\u003c/p\u003e","description":"","filename":"floatimage13.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/7c65daaf19bd6ce9a9549cea.jpeg"},{"id":74265315,"identity":"add7fc13-ef56-449f-a8e7-a3d69ecf2ab3","added_by":"auto","created_at":"2025-01-20 12:54:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1444857,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4405209/v1/17041bfd-974e-4c2f-9e67-eddd0ee3afaa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The impact of changes in LH levels in flexible antagonist protocols on the clinical outcomes of fresh IVF/ICSI cycles in populations of POSEIDON groups 1 and 2: a retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDuring the decades of flourishing advances in assisted reproductive technology, many ovulation induction regimens have been developed. However, currently, the most commonly used and prevalent regimens in clinical practice are the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-A regimens. Compared with the GnRH-a regimen, the GnRH-A regimen exhibits advantages such as short treatment time, low Gn dosage, flexible medication, rapid inhibition of LH peak, and low incidence of ovarian hyper-stimulation syndrome (OHSS). It is the most commonly used controlled ovulation induction regimen for high ovarian response (HOR) and poor ovarian response (POR). Although experts from China have reached a consensus on the standardized application of GnRH-A regimens[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], clinicians still need to continuously explore and improve the control and optimization of key nodes in the use of GnRH-A regimens in practice. In the process of antagonist therapy in COS, reasonably controlling the serum LH value is challenging. Early onset and sudden LH peaks can lead to premature luteinization of follicles, affecting the rate of egg retrieval and endometrial receptivity. However, LH itself is a substrate for estrogen synthesis and is essential in the middle and late stages of follicular development and final maturation. Excessive suppression of LH may lead to a high proportion of immature eggs and insufficient luteal function [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Recent studies have reported that baseline LH and LH fluctuations during the antagonist COS process do not affect the clinical outcomes of patients. Even if LH temporarily increases, timely addition of antagonists and rapid decrease in LH levels will not have adverse effects on the clinical outcomes of IVF [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, previous studies have mostly focused on the HOR or entire population, and only few reports have focused on the regulation of antagonist regimens in the POR population. In clinical practice, it is difficult to precisely regulate the level of LH in individuals. Therefore, in this study, we focused on elucidating a more convenient observation method to control the nodes and optimize the clinical outcomes of patients.\u003c/p\u003e \u003cp\u003ePreviously, the Bologna criteria were often used to define POR. In 2016, the POSEIDON group shifted its focus from \u0026ldquo;low responsiveness\u0026rdquo; to \u0026ldquo;low prognosis\u0026rdquo; and proposed a POSEIDON stratification approach, dividing the POR population into four subgroups. Among them, groups 1 and 2 had normal ovarian reserve function (AFC\u0026thinsp;\u0026ge;\u0026thinsp;5 and AMH\u0026thinsp;\u0026ge;\u0026thinsp;1.2 ng/mL); however, unexpected POR or suboptimal response occurred [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Regulating the COS regimen in this population can achieve the same live birth rate as the population with normal ovarian response [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In this study, we retrospectively analyzed the population of POSEIDON groups 1 and 2 who underwent IVF/ICSI with flexible antagonist regimen. Furthermore, the correlation between changes in LH level during the COS process and clinical outcomes of fresh cycle were investigated. This study can help clinicians to assess the COS process with antagonist protocol, optimize the ovulation promotion plan, and improve clinical outcomes of patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e1.1 Research subjects and grouping\u003c/p\u003e \u003cp\u003eRetrospective analysis was performed using clinical data of POSEIDON groups 1 and 2 treated with the flexible IVF/ICSI regimen of GnRH-A at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital from January 2017 to December 2022. The inclusion criteria were as follows: 1) POSEIDON group 1 population [age\u0026thinsp;\u0026lt;\u0026thinsp;35 years, normal ovarian reserve function (AFC\u0026thinsp;\u0026ge;\u0026thinsp;5 and AMH\u0026thinsp;\u0026ge;\u0026thinsp;1.2 ng/mL)] with unexpected ovarian low response or suboptimal response (number of retrieved eggs\u0026thinsp;\u0026le;\u0026thinsp;9) or POSEIDON group 2 population [age\u0026thinsp;\u0026ge;\u0026thinsp;35 years and normal ovarian reserve function (AFC\u0026thinsp;\u0026ge;\u0026thinsp;5 and AMH\u0026thinsp;\u0026ge;\u0026thinsp;1.2 ng/mL)] with unexpected ovarian low response or suboptimal response (number of retrieved eggs\u0026thinsp;\u0026le;\u0026thinsp;9); 2) Flexible COS using antagonists. Exclusion criteria: 1) polycystic ovary syndrome; 2) multiple uterine fibroids (or single fibroid\u0026thinsp;\u0026ge;\u0026thinsp;5 cm); 3) history of intrauterine adhesions; 4) ovarian tumors; 5) uterine adenomyosis; 6) endometriosis uterine malformation; and 7) chromosomal abnormalities in either spouse causing recurrent implantation failure (RIF) or recurrent miscarriage (RSA).\u003c/p\u003e \u003cp\u003eAccording to the value of LH change [(LH level on the trigger day\u0026thinsp;\u0026minus;\u0026thinsp;baseline LH)/baseline LH], the study subjects were divided into 7 groups: groups A, B, C, D, E, F, and G with the value of LH change\u0026thinsp;\u0026ge;\u0026thinsp;100%, \u0026ge; 50% to \u0026lt;\u0026thinsp;100%, \u0026ge; 25% to \u0026lt;\u0026thinsp;50%, \u0026ge; 0% to \u0026lt;\u0026thinsp;25%, \u0026ge; \u0026minus;25\u0026ndash;0%, \u0026ge; \u0026minus;50% to \u0026minus;\u0026thinsp;25%, and \u0026ge;\u0026thinsp;\u0026minus;\u0026thinsp;100% to \u0026minus;\u0026thinsp;50%, respectively.\u003c/p\u003e \u003cp\u003e1.2 Flexible GnRH-A regimens\u003c/p\u003e \u003cp\u003eStarting from the days 2\u0026ndash;5 of menstruation, Gn [Recombinant Human Follitropin Alfa Solution for Injection (Merck, Germany; Procon, Merck, USA) or Urofollitropin for Injection (Zhuhai Lizhu Pharmaceutical Company)] was administered with an initial dose of 100\u0026ndash;600 IU after considering the patient\u0026rsquo;s age, body mass index(BMI), AMH, basal follicle stimulating hormone (FSH), and antral follicle count (AFC) levels. After Gn activation, serum FSH, LH, estradiol (E2), and progesterone (Prog) levels were checked every 3\u0026ndash;5 days. Antagonist was added when the diameter of the dominant follicle reached 14 mm or approximately 15 mm or when the diameter of the dominant follicle was \u0026gt;\u0026thinsp;12 mm and E2\u0026thinsp;\u0026gt;\u0026thinsp;300 ng/L (1 ng/L\u0026thinsp;=\u0026thinsp;3.672 pmol/L). The dosage was adjusted till trigger day based on the follicle size and hormone levels. When the diameter of 3 dominant follicles was \u0026ge;\u0026thinsp;17 mm, that of 2 dominant follicles was \u0026ge;\u0026thinsp;18 mm, or that of 1 dominant follicle was \u0026ge;\u0026thinsp;20 mm, trigger was induced by administering recombinant human chorionic gonadotropin(hCG) (Aize, Merck, Switzerland) 250 \u0026micro;g or hCG (Zhuhai Lizhu Group Lizhu Pharmaceutical Factory) 6000\u0026ndash;10,000 IU. Egg retrieval was performed after 36 h.\u003c/p\u003e \u003cp\u003e1.3 Laboratory indicators\u003c/p\u003e \u003cp\u003eThe cleavage stage embryos and blastocysts were evaluated based on the consensus of Chinese experts on morphological evaluation of human cleavage-stage embryos and blastocysts [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The laboratory indicators included number of retrieved eggs, rate of egg retrieval, number of fertilization (2PN), fertilization rate, number of cleavage, cleavage rate, number of excellent embryos, rate of excellent embryos, number of blastocysts, and rate of blastocyst formation. The relevant indicators were assessed via referring to the consensus of experts on quality control of clinical key indicators of assisted reproductive technology, which included\u003c/p\u003e \u003cp\u003eegg retrieval rate = (the number of eggs retrieved/number of follicles penetrated) \u0026times; 100%\u003c/p\u003e \u003cp\u003efertilization rate (2PN fertilization rate) = (number of double pronuclear fertilizations/number of retrieved eggs) \u0026times; 100%\u003c/p\u003e \u003cp\u003ecleavage rate = (number of cleavage/number of double pronuclear fertilization) \u0026times; 100%\u003c/p\u003e \u003cp\u003eexcellent embryo rate = (number of excellent embryos/number of cleavage) \u0026times; 100%\u003c/p\u003e \u003cp\u003eblastocyst formation rate = (number of blastocysts/number of blastocyst cultures) \u0026times; 100%.\u003c/p\u003e \u003cp\u003e1.4 Clinical indicators\u003c/p\u003e \u003cp\u003eClinical indicators included fresh cycle clinical pregnancy rate and live birth rate, which were calculated as follows:\u003c/p\u003e \u003cp\u003eclinical pregnancy rate (per fresh transplant cycle) = (number of clinical pregnancy cycles/number of fresh transplant cycles) \u0026times; 100%\u003c/p\u003e \u003cp\u003elive birth rate (per fresh transfer cycle) = (number of live births/number of fresh embryo transfer cycles) \u0026times; 100%.\u003c/p\u003e \u003cp\u003e1.5 Statistical analysis\u003c/p\u003e \u003cp\u003eSPSS23.0 was used for statistical analysis. Quantitative data that conform to normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Further, homogeneity of variance testing was performed. Data with homogeneity of variance were analyzed using two independent sample t-tests. Non-normally distributed data were represented by median and interquartile intervals. Kruskal Wallis H-test (KW test) was used for intergroup comparisons, and Bonferroni method was used for pairwise comparisons between groups. Data were subjected to χ2 test. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eData from 733 eligible patients were included, with 25, 33, 31, 53, 78, 148, and 365 cases in groups A, B, C, D, E, F, and G, respectively. Moreover, there were 467 fresh transplant cycles, 173 clinical pregnancies, and 130 live births.\u003c/p\u003e\n\u003cp\u003e2.1 Comparison of general information of patients in each group\u003c/p\u003e\n\u003cp\u003eNo significant differences were observed in terms of the types of infertility, years of infertility, total Gn, baseline FSH, and Prog level and endometrial thickness on the trigger day among the groups (P values\u0026thinsp;\u0026ge;\u0026thinsp;0.05). The differences were significant among groups in terms of age, BMI, time to antagonist addition, initial Gn dose, Gn days, baseline LH, baseline AMH, LH and E2 levels on the trigger day (all P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of general information\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eA\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eB\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eF\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eG\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34.24\u0026thinsp;\u0026plusmn;\u0026thinsp;5.60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.40\u0026thinsp;\u0026plusmn;\u0026thinsp;5.53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.10\u0026thinsp;\u0026plusmn;\u0026thinsp;5.22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.00(10.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.00(8.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34.00(7.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.00(6.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.29\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.72(3.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.03(3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.77(3.79)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.29(4.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.23(4.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eprimary infertility\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11/25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10/33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15/31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19/53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27/78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60/148\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e151/365\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.237\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esecondary infertility\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14/25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23/33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16/31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34/53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51/78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e88/148\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e214/365\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eyears of infertility\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(5.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(4.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.00(3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(5.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(3.75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.435\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003etime to antagonist addition\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.00(2.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.00(1.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.00(3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.00(1.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.024\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003einitial Gn dose\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(25.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(75.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(25.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(0.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(0.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(25.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225.00(50.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003etotal Gn\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2555.00\u0026thinsp;\u0026plusmn;\u0026thinsp;767.20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2400.00(1387.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2125.00(600.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2400.00(1012.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2250.00(743.75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2250.00(900.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2250.00(875.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.158\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGn days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.56\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.00(3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.00(2.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.008\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ebaseline FSH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.42(3.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.67(2.87)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.03(2.55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.54(2.52)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.77(2.43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.290\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ebaseline LH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.74(1.12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.20(1.60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.30(1.70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.60(1.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00(1.74)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.70(1.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAMH\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.86(1.21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.72(0.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.09(1.57)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.87(1.89)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.96(1.72)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.23(1.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.47(2.16)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLH on the trigger day\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.60(4.45)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.69(2.55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.30(1.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.22(1.44)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.90(1.10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.00(0.70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eE2 on the trigger day\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1045.00(1551.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1227.00(1412.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1454.00(1248.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1535.00(994.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1361.00(1260.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1482.50(1559.25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1912.00(1599.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProg on the trigger day\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.50(0.59)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.60(0.46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.70(0.57)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.56(0.41)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.60(0.40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.54(0.50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.60(0.60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.734\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eendometrial thickness on the trigger day\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.00(1.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.00(2.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.80(2.60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.817\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003e\u003cem\u003eNote\u003c/em\u003e Quantitative data that conform to normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.Non-normally distributed data were represented by median and interquartile intervals. BMI: body mass index; Gn: gonadotropin; FSH: follicle stimulating hormone; LH: luteinizing hormone; E2: estradiol\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eFurther grouping comparison indicated that in terms of age, only group E patients were significantly older than group G patients (P\u0026thinsp;=\u0026thinsp;0.000). The other components exhibited no significant differences (all P values\u0026thinsp;\u0026ge;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). In terms of BMI, time for antagonist addition, and Gn days, the differences were not significant among groups (all P values\u0026thinsp;\u0026ge;\u0026thinsp;0.05; Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). In terms of initial Gn dose, the median for each group was 225 IU. However, significant difference was observed between groups G and D (P\u0026thinsp;=\u0026thinsp;0.028), as well as between group G and E (P\u0026thinsp;=\u0026thinsp;0.036; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). In terms of baseline LH, groups F and G exhibited significantly higher baseline LH values than other groups (all P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). In terms of basic AMH, group G exhibited higher level, which was significantly different compared with that in groups B and E (P\u0026thinsp;=\u0026thinsp;0.003 and 0.036, respectively; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e). In terms of daily LH in hCG, significant differences were observed among the groups (all P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e). In terms of E2 on hCG day, only group E exhibited significantly lower value than group G (P\u0026thinsp;=\u0026thinsp;0.042; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e2.2 Comparison of laboratory indicators and clinical outcomes among various groups\u003c/p\u003e\n\u003cp\u003eNo significant difference (P\u0026thinsp;\u0026ge;\u0026thinsp;0.05) was observed among the groups in terms of egg retrieval rate, fertilization rate, cleavage rate, excellent embryo rate, blastocyst number, and blastocyst formation rate. However, significant difference (P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was observed in terms of number of retrieved eggs, mature egg number, fertilization number (2PN number), number of cleavage, and excellent embryo number (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, although no significant difference was observed among the groups in terms of the number of blastocysts, the groups with reducing in LH level (D, E, F, and G) generally had higher blastocyst numbers than those with increasing LH level (A, B, and C).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of laboratory indicators\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eA\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eB\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eF\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eG\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ethe number of eggs retrieved\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.76\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.58\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.82\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.29\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eegg retrieval rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e75.35\u0026thinsp;\u0026plusmn;\u0026thinsp;33.70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e90.82\u0026thinsp;\u0026plusmn;\u0026thinsp;15.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e88.23\u0026thinsp;\u0026plusmn;\u0026thinsp;18.27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e88.79\u0026thinsp;\u0026plusmn;\u0026thinsp;18.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e89.64\u0026thinsp;\u0026plusmn;\u0026thinsp;16.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e89.36\u0026thinsp;\u0026plusmn;\u0026thinsp;18.41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e89.46\u0026thinsp;\u0026plusmn;\u0026thinsp;16.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.575\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003emature egg number\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;2.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.42\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.84\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.94\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.44\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.98\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enumber of double pronuclear fertilizations (2PN)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.84\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.07\u0026thinsp;\u0026plusmn;\u0026thinsp;2.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003efertilization rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e73.95\u0026thinsp;\u0026plusmn;\u0026thinsp;35.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e83.15\u0026thinsp;\u0026plusmn;\u0026thinsp;26.95\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e75.67\u0026thinsp;\u0026plusmn;\u0026thinsp;25.69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e80.19\u0026thinsp;\u0026plusmn;\u0026thinsp;26.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e82.19\u0026thinsp;\u0026plusmn;\u0026thinsp;20.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e77༎71\u0026thinsp;\u0026plusmn;\u0026thinsp;26.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e82.00\u0026thinsp;\u0026plusmn;\u0026thinsp;21.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.565\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enumber of cleavage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.64\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.28\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.79\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ecleavage rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e86.00\u0026thinsp;\u0026plusmn;\u0026thinsp;33.22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e88.08\u0026thinsp;\u0026plusmn;\u0026thinsp;28.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e91.61\u0026thinsp;\u0026plusmn;\u0026thinsp;20.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e86.20\u0026thinsp;\u0026plusmn;\u0026thinsp;27.42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e95.23\u0026thinsp;\u0026plusmn;\u0026thinsp;9.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e91.00\u0026thinsp;\u0026plusmn;\u0026thinsp;23.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e92.28\u0026thinsp;\u0026plusmn;\u0026thinsp;18.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.907\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ecleavage rate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e1.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e2.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eexcellent embryo rate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e61.22\u0026thinsp;\u0026plusmn;\u0026thinsp;37.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e54.61\u0026thinsp;\u0026plusmn;\u0026thinsp;37.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e56.68\u0026thinsp;\u0026plusmn;\u0026thinsp;32.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e63.84\u0026thinsp;\u0026plusmn;\u0026thinsp;33.19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e64.03\u0026thinsp;\u0026plusmn;\u0026thinsp;32.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e59.31\u0026thinsp;\u0026plusmn;\u0026thinsp;32.10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e59.82\u0026thinsp;\u0026plusmn;\u0026thinsp;30.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.635\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enumber of blastocysts\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.082\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eblastocyst formation rate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e25.40\u0026thinsp;\u0026plusmn;\u0026thinsp;42.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e26.77\u0026thinsp;\u0026plusmn;\u0026thinsp;39.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e27.42\u0026thinsp;\u0026plusmn;\u0026thinsp;41.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e37.86\u0026thinsp;\u0026plusmn;\u0026thinsp;42.40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e33.17\u0026thinsp;\u0026plusmn;\u0026thinsp;36.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e38.50\u0026thinsp;\u0026plusmn;\u0026thinsp;42.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e39.14\u0026thinsp;\u0026plusmn;\u0026thinsp;41.44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.246\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003e\u003cem\u003eNote\u003c/em\u003e Quantitative data that conform to normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn terms of the number of eggs retrieved, group A exhibited significantly lower number than groups E, F, and G (P\u0026thinsp;=\u0026thinsp;0.042, 0.011, and 0.0000, respectively) and group B exhibited significantly lower number than group G (P\u0026thinsp;=\u0026thinsp;0.013; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e10\u003c/span\u003e). In terms of the number of mature eggs, group A exhibited significantly lower number than groups E, F, and G (P\u0026thinsp;=\u0026thinsp;0.023, 0.017, and 0.0000, respectively) and group B exhibited significantly lower number than group G (P\u0026thinsp;=\u0026thinsp;0.005; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e11\u003c/span\u003e). In terms of fertilization number (2PN number), group A exhibited significantly lower number than groups E, F, and G (P\u0026thinsp;=\u0026thinsp;0.016, 0.033, and 0.000, respectively; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e12\u003c/span\u003e). In terms of cleavage count, group A exhibited significantly lower value than groups E and G (P\u0026thinsp;=\u0026thinsp;0.035 and 0.0000, respectively; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e13\u003c/span\u003e). No significant difference was observed in terms of clinical pregnancy rate and live birth rate among the groups (P\u0026thinsp;\u0026ge;\u0026thinsp;0. 05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of clinical outcomes\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e组别\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;100%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;50\u0026thinsp;~\u0026thinsp;\u0026lt;\u0026thinsp;100%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;25%~\u0026lt;50%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;0\u0026thinsp;~\u0026thinsp;\u0026lt;\u0026thinsp;25%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;-25%~0\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;-50%~-25%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026ge;-100%~-50%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026chi;2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eB\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eE\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eF\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eclinical pregnancy rate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4/13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7/25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6/19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13/35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17/55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35/89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e91/231\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.973\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.151\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003elive birth rate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2/4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6/7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6/6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10/13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10/17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29/35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e67/91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.036\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.284\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"10\"\u003e\u003cem\u003eNote\u003c/em\u003e clinical pregnancy rate\u0026thinsp;=\u0026thinsp;number of clinical pregnancy cycles/number of fresh transplant cycles;live birth rate\u0026thinsp;=\u0026thinsp;number of live births/number of fresh embryo transfer cycles.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eLH is crucial for the development of follicles. In the middle and late stages of follicular development, granulosa cells also have LH receptors that can promote follicle maturation and induce ovulation. Particularly for patients with POR, adding LH appropriately can achieve better clinical outcomes [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Previous studies have proposed the concept of \u0026ldquo;LH treatment window,\u0026rdquo; believing that LH levels above or below the threshold level will lead to insufficient E2 levels, thereby affecting follicular development [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Some studies suggested that the rate and direction of LH changes determine follicular development, and basline LH values and LH fluctuations before the addition of antagonists do not affect patient outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, Zhang believed that although the application of antagonists can inhibit LH surge, it will have adverse effects on embryonic development and pregnancy outcomes in fresh transfer cycles [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, the control of LH levels during the process of ovulation promotion is debatable. The key to the flexible use of antagonists lies in how to regulate LH levels during the COS process through timely and appropriate addition of antagonists, thereby improving patient egg retrieval, embryo retrieval, and clinical outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In clinical practice, medication dosage is generally adjusted every few days based on the patient\u0026rsquo;s follicular development and hormonal changes. It is difficult to accurately control the LH changes at each time node, and the global view of LH fluctuations can only be reflected on the trigger day. If unexpected LH fluctuations occur, timely remedies may not be possible. Therefore, it is necessary to explore a more convenient and intuitive way to describe LH fluctuations and guide clinicians to regulate serum LH values based on outcomes. In this study, the patients were divided based on overall changes in LH during the COS process (LH level on the trigger day\u0026thinsp;\u0026minus;\u0026thinsp;baseline LH), and the laboratory and clinical outcomes of each group were compared. Compared with the patients with an increase in LH levels by \u0026ge;\u0026thinsp;100%, those with a decrease in LH levels exhibited more number of retrieved eggs, mature eggs, 2PN, cleavage, and blastocysts. Among them, group G exhibited superior performance (LH change\u0026thinsp;\u0026ge;\u0026thinsp;\u0026minus;\u0026thinsp;100% to \u0026minus;\u0026thinsp;50%); however, no significant difference was observed in terms of the number of superior embryos, clinical pregnancy, and live birth outcomes among the groups. This is similar to the research findings of Wang and Ji, who believed that LH levels on trigger day are negatively correlated with the number of retrieved eggs but have no significant impact on the clinical pregnancy outcomes of patients [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This suggested that during the COS process, maintaining the LH level within the range of 0\u0026ndash;100% lower than the baseline (with \u0026ge;\u0026thinsp;\u0026minus;\u0026thinsp;100% to \u0026minus;\u0026thinsp;50% being optimal) can lead to better egg and embryo outcomes.\u003c/p\u003e \u003cp\u003ePatients with low ovarian response have poorer pregnancy outcomes via assisted reproductive technology (ART) and higher treatment costs compared with those with normal ovarian response. However, if the COS regimen can be reasonably grasped, they can achieve the same clinical outcomes as the normal population [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This study targeted the population of POSEIDON groups 1 and 2, as their ovarian reserve function is still acceptable but they exhibit unexpected low responses resulting in suboptimal egg retrieval. Previous studies have suggested that this may be related to mutations in Gn receptor genes or single nucleotide polymorphisms (SNPs) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Some scholars also believe that this may be related to the low initial dose of Gn [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In the early stages of COS, the application of exogenous Gn can stimulate the secretion of gonadotropin large inhibitory factor (GnSAF) in the ovaries. Studies have reported that during the ART cycle, GnSAF is secreted by follicles smaller than 11 mm; its biological activity is the highest in the early and middle stages of follicular development, gradually decreasing in the late stage. It can reduce the pituitary gland\u0026rsquo;s responsiveness to Gn by inhibiting the positive feedback effect of estrogen, thereby regulating LH secretion. Therefore, for POR, a sufficient amount of Gn activation can ensure the secretion of GnSAF and prevent premature LH peak [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In this study, the median initial Gn dose for each group was 225 IU; however, the difference was significant as revealed by K-W test. Specifically, group G exhibited a lower initial Gn dose than groups D and E (the average initial Gn dose for groups D, E, and G was 230.90 (221.18\u0026ndash;240.61), 233.17 (221.88\u0026ndash;244.46), and 210.79 (205.75\u0026ndash;215.83), respectively]. Due to the minimum fine-tuning unit of Gn being 12.5\u0026ndash;25 IU, the precise control range is limited in practical operation. Therefore, we suggest that the Gn activation amount can be based on 225 IU, combined with patient age, BMI, basic AMH, AFC, and comprehensive control of previous COS process.\u003c/p\u003e \u003cp\u003eIn summary, our study suggested that using a flexible antagonist regimen to induce ovulation in the POSEIDON groups 1 and 2 can lead to better clinical outcomes by adjusting the dosage of Gn and antagonists during the COS process, to control the LH level on trigger day and allow it to decrease within the range of 0\u0026ndash;100% from baseline (with \u0026ge;\u0026thinsp;\u0026minus;\u0026thinsp;100% to \u0026minus;\u0026thinsp;50% being optimal). The limitations of this study are detailed grouping and small sample size in some groups. Moreover, this was a single-center retrospective study. In future, we will conduct multicenter studies, increase sample size, and explore the key node control of flexible antagonist strategies in detail.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our thanks to Bullet Edits Limited for their assistance in the linguistic editing and proofreading of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZBH contributed to the research design. ZY collected the patient data. ZY, LYY, CLL, HLS and YYZ analyzed and interpreted the patient data. ZY and ZBH were involved in the manuscript development. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from the Natural Science Foundation of Fujian Province (No. 2023J011229).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in accordance with the Declaration of Helsinki and was approved by the Medical Research Ethics Committee of Fujian Maternity and Child Health Hospital (Ethics approval number: 2024KY057). All patients are exempt from informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eExpert Consensus Compilation Group of Reproductive Medicine Committee of China Medical Women\u0026apos;s Association. Expert consensus on standardized application of antagonist protocol in assisted reproductive technology[J]. Chin J Reprod Contracep, 2022 , 42 (2): 109 -116. DOI: 10 .3760/ cma.j.cn101441-20211108-00495.\u003c/li\u003e\n\u003cli\u003eWang M, Xi Q, Yang Q, et al.The relationship between a novel evaluation parameter of premature luteinization and IVF outcomes[J/OL]. Reprod Biomed Online, 2021 , 42(2): 323-331. DOI: 10.1016/j.rbmo.2020.20.009.\u003c/li\u003e\n\u003cli\u003eLiu Z , Wang K H .Effect of basal luteinizing hormone (bLH) level on in vitro fertilization/intra-cytoplasmic injections (IVF/ICSI) outcomes in polycystic ovarian syndrome (PCOS) patients[J].BMC Pregnancy and Childbirth, 2023, 23(1).DOI:10.1186/s12884-023-05944-4.\u003c/li\u003e\n\u003cli\u003eHuang JD, Yang RX, Dong XZ, et al. The Effect of Early Elevation of LH in GnRH Antagonist Protocol on Clinical Outcomes of IVF/ICSI Fresh Embryo Transfer: A Propensity Score Matching Study [J]. Chinese Journal of Reproduction and Contraception, 2023, 43(12): 1244-1248. DOI: 10.3760/cma.j.cn101441-20221116-00511.\u003c/li\u003e\n\u003cli\u003eXiao S, Mo ML, Liu S, et al. Impact of early onset LH elevation in antagonist regimens on clinical outcomes of IVF-ET in patients with polycystic ovary syndrome[J]. J Repord Med, 2022, 31(1): 6-12. DOI: 10.3969/j.issn.10043845.2022.01.002.\u003c/li\u003e\n\u003cli\u003eAlviggi C , Andersen C Y , Buehler K ,et al. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept[J].Fertility \u0026amp; Sterility, 2016:1452-1453.DOI:10.1016/j.fertnstert.2016.02.005.\u003c/li\u003e\n\u003cli\u003eParimala C , Belavendra A , Mangalaraj A M ,et al. POSEIDON classification and the proposed treatment options for groups 1 and 2: time to revisit? A retrospective analysis of 1425 ART cycles[J].Human Reproduction Open(1):1[2024-02-06].DOI:10.1093/hropen/hoaa070.\u003c/li\u003e\n\u003cli\u003eChinese Association of Reproductive Medicine. Expert consensus on human embryo morphological assessment: cleavage-stage embryos and blastocysts grading criteria[J]. Chin J Reprod Contracep, 2022 , 42 (12): 1218 -1225. DOI: 10.3760/cma.j.cn101441-20220619-00266.\u003c/li\u003e\n\u003cli\u003eConforti A , Esteves S C , Di Rella F ,et al.The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: A systematic review and meta-analysis[J].Reproductive Biology and Endocrinology, 2019, 17(1).DOI:10.1186/s12958-019-0460-4.\u003c/li\u003e\n\u003cli\u003eWang L, Wang J, Gao Y, et al. Effects of different exogenous LH activity drugs on pregnancy outcomes in patients with suboptimal ovarian response: a retrospective cohort study,Chinese Journal of Reproduction and Contraception.2023,43(08)：769-776.DOI:10.3760/cma.j.cn101441-20220406-00144.\u003c/li\u003e\n\u003cli\u003eFischer R, Nakano FY, Roque M, et al. A quality management approach to controlled ovarian stimulation in assisted reproductive technology: the \u0026quot;Fischer protocol\u0026quot;[J]. Panminerva Med, 2019, 61(1): 11-23. DOI: 10.23736/ S0031-0808.18.03549-8.\u003c/li\u003e\n\u003cli\u003eShoham Z .The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation[J].Fertility and Sterility, 2002.DOI:10.1016/S0015-0282(02)03157-6.\u003c/li\u003e\n\u003cli\u003eOrvieto R , Venetis C A , Fatemi H M ,et al.Optimising Follicular Development, Pituitary Suppression, Triggering and Luteal Phase Support During Assisted Reproductive Technology: A Delphi Consensus[J].Frontiers in endocrinology, 2021, 12:675670.DOI:10.3389/fendo.2021.675670.\u003c/li\u003e\n\u003cli\u003eHuirne J A F , Van L A C D , Roel S ,et al.Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy[J].Human Reproduction(2):359-67[2024-02-08].DOI:10.1093/humrep/deh601.\u003c/li\u003e\n\u003cli\u003eZhou J S , Chen J H , Tang F F ,et al.The effect of luteinizing hormone changes in GnRH antagonist protocol on the outcome of controlled ovarian hyperstimulation and embryo transfer[J].BMC Pregnancy and Childbirth, 2023, 23(1).DOI:10.1186/s12884-023-05916-8.\u003c/li\u003e\n\u003cli\u003eZhang D , Zhang D , Sun Z ,et al.The effect of a transient premature luteinizing hormone surge without elevated serum progesterone on invitro fertilization outcomes in a gonadotropin-releasing hormone antagonist flexible protocol[J].Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2019:1-4.DOI:10.1080/09513590.2019.1683730.\u003c/li\u003e\n\u003cli\u003eWang AC, Wang Y, Wu FX, et al. Assessing predictors for the success of GnRH antagonist protocol in reproductive women in IVF/ICSI - in fresh cycles. Biomed Rep. 2017;7(5):482\u0026ndash;6. DOI:10.3892/br.2017.984.\u003c/li\u003e\n\u003cli\u003eJi Hui C, Meng-xi Z, Chun, et al. Effect of LH level on pregnancy outcome of IVF during controlled ovarian hyperstimulation with antagonist protocol. J Reprod Med. 2017;26(10):972\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eAlviggi C，Conforti A，Santi D，et a1．Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation：a systematic review and meta analysis[J]．Hum Reprod Update，2018，24：599\u0026mdash;614．DOI：10.1093/humupd/dmy019.\u003c/li\u003e\n\u003cli\u003eK\u0026ouml;nig TE, van der Lee J, Schats R, et al. The relationship between FSH receptor polymorphism status and IVF cycle outcome: a retrospective observational study. Reprod Biomed Online. 2019 Aug;39(2):231-240. DOI: 10.1016/j.rbmo.2019.05.018.\u003c/li\u003e\n\u003cli\u003eDrakopoulos P, Santos-Ribeiro S, Bosch E, et al. The Effect of Dose Adjustments in a Subsequent Cycle of Women With Suboptimal Response Following Conventional Ovarian Stimulation. Front Endocrinol (Lausanne). 2018 Jul 23;9:361. DOI: 10.3389/fendo.2018.00361.\u003c/li\u003e\n\u003cli\u003eMessinis IE, Messini CI, Anifandis G, et al. Gonadotropin Surge-Attenuating factor: a nonsteroidal ovarian hormone Controlling GnRH-Induced LH Secretion in the normal menstrual cycle. Vitam Horm. 2018;107:263\u0026ndash;86. DOI:10.1016/bs.vh.2018.01.002.\u003c/li\u003e\n\u003cli\u003eLiu XH, Wu XH. Research progress of gonadotropin inhibitory hormone in female reproduction [J]. Chinese Journal of Birth Health \u0026amp; Heredity, 2018, 26(2):3. DOI: CNKI:SUN:ZYYA.0.2018-02-048.\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":"POSEIDON groups 1 and 2, flexible GnRH-A regimen, changes in LH levels","lastPublishedDoi":"10.21203/rs.3.rs-4405209/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4405209/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective: To investigate the impact of changes in luteinizing hormone (LH) levels during ovulation induction using flexible gonadotropin-releasing hormone antagonist (GnRH-A) regimens in POSEIDON groups 1 and 2 on the clinical outcomes of fresh in-vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) cycles.\u003c/p\u003e\n\u003cp\u003eMethod: A retrospective analysis was conducted on the clinical data of females in POSEIDON groups 1 and 2 who underwent the IVF/ICSI used flexible GnRH-A regimen at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital from January 2017 to December 2022. According to the values of change in LH [(LH level on the trigger day − baseline LH)/baseline LH], the study subjects were divided into 7 groups. The general information, laboratory indicators, and clinical outcomes of each group were compared.\u003c/p\u003e\n\u003cp\u003eResults: Significant difference was observed in terms of the number of retrieved eggs, mature eggs, fertilization number (2PN number), cleavage, and excellent embryos among all groups (all P values \u0026lt; 0.05). The number of eggs retrieved in group A was significantly lower than that in groups E, F, and G (P = 0.042, 0.011, and 0.000, respectively). The number of eggs retrieved in group B was significantly lower than that in group G (P = 0.013). The number of mature eggs in group A was significantly lower than that in groups E, F, and G (P = 0.017, 0.023, and 0.000, respectively). Group B exhibited significantly lower number of mature eggs than group G (P = 0.005). The 2PN number in group A was significantly lower than that in groups E, F, and G (P = 0.033, 0.016, and 0.000, respectively). The cleavage count of group A was significantly lower than that of groups E and G (P = 0.035 and 0.000, respectively).\u003c/p\u003e\n\u003cp\u003eConclusion: The use of a flexible GnRH-A regimen to induce ovulation in the POSEIDON groups 1 and 2 can lead to better clinical outcomes. This involves adjusting the dosage of gonadotropin(Gn) and antagonists during the controlled ovarian stimulation(COS) process, to control the LH level on trigger day and allow it to decrease within the range of 0%–100% from baseline (with optimal range being ≥ −100% to −50%).\u003c/p\u003e","manuscriptTitle":"The impact of changes in LH levels in flexible antagonist protocols on the clinical outcomes of fresh IVF/ICSI cycles in populations of POSEIDON groups 1 and 2: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-29 02:43:15","doi":"10.21203/rs.3.rs-4405209/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":"168acc04-fc87-4019-9d50-18b6c6bf9f07","owner":[],"postedDate":"May 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-20T12:53:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-29 02:43:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4405209","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4405209","identity":"rs-4405209","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}