Granulocyte colony-stimulating factor priming improves egg and embryo quality in patients with poor ovarian reserve: a retrospective case study

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We retrospectively investigated whether G-CSF priming on superovulation initiation day with assisted reproductive technology (ART) improved egg maturation and embryonic development in patients with poor ovarian reserve. Methods In this retrospective clinical case study, 174 patients aged 20 to 45 years were divided into a test group(40 patients each) and a control group (134 patients each) based on whether or not they used G-CSF. All patients in the priming group but not the control group received subcutaneous G-CSF priming injection on superovulation initiation day. Then, each group underwent 1 cycle of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), because all groups adopted PPOS protocol, which required freezing of all transferable embryos, and thawing embryos for transfer. Results Before propensity score matching, there were statistically significant differences in number of 2PN(6.4 ± 3.74 vs4.3 ± 2.44, P = 0.001), number of eggs retrievals(8.3 ± 4.16 vs 6.0 ± 3.26, P = 0.003), number of total fertilization(7.1 ± 3.69 vs 4.8 ± 2.54, P = 0), number of transferable embryos(6.6 ± 3.74 vs 4.3 ± 2.39, P = 0) and number of cleavage(7.1 ± 3.75 vs 4.6 ± 2.44, P = 0) were significantly improved by priming. After the propensity score matching(1:1),There were statistically significant differences in number of MII (4.9 ± 5.15 vs 6.4 ± 2.77 P = 0).The number of 2PN (5.9 ± 3.55 vs 4.6 ± 2.22, P = 0.1), number of eggs retrievals(7.9 ± 4.17 vs 6.6 ± 2.77, P = 0.3), number of total fertilization(6.9 ± 3.57 vs 5.3 ± 2.39, P = 0.1), number of transferable embryos(6.3 ± 3.58 vs 4.8 ± 1.92,P = 0.1) and number of cleavage(6.8 ± 3.64 vs 5.1 ± 2.24, P = 0.1) tended to be higher in 33 G-CSF patients than in 33 controls, although statistical significance was not attained respectively. After matching propensity scores(1:2),there were statistically significant differences in number of transferable embryos(6.4 ± 3.62 vs 4.8 ± 2.49, P = 0.045), were significantly improved by priming. The number of 2PN (5.9 ± 3.60 vs 4.8 ± 2.77, P = 0.17), number of eggs retrievals (8.0 ± 4.30 vs 6.9 ± 3.64, P = 0.285), number of total fertilization (6.9 ± 3.64 vs 5.5 ± 2.84, P = 0.087), and number of cleavage (6.8 ± 3.71 vs 5.3 ± 2.73, P = 0.08) tended to be higher in 31 G-CSF patients than in 52 controls, although statistical significance was not attained respectively. In addition, the G-CSF patients achieved more cryopreservation of transplantable embryos than the control group. Conclusion The administration of G-CSF during Superovulation day of ART cycle can improve embryonic development potential of patients with poor ovarian reserve, with a view to improving future clinical pregnancy rates and live birth rates. Biological sciences/Drug discovery Health sciences/Medical research Granulocyte colony-stimulating factor poor ovarian response number of transferable embryos number of eggs retrievals propensity score matching Figures Figure 1 Introduction In diabetic rats, G-CSF consistently reduced ovarian follicular degeneration and ovarian stromal degeneration and rupture, while increasing the number of presinus follicles [ 1 ] G-CSF also significantly increased periluminal follicles and serum AMH in rats with cisplatin induced ovarian reserve decline [ 2 ] Considering the role of G-CSF in animal models, in 2022 we gave G-CSF to patients with poor ovarian reserve simultaneously during superovulation. We observed that in patients with ART(who were not given G-CSF)during hyperovulation serum G-CSF concentrations were lowest at the follicular stage ,highest on trigger day ,decreased after egg retrieval ,ang were higher in follicular fluid than in serum .In the future, we can compare the experimental group with the control group to observe congenital abnormalities and weight difference between all the infants treated with G-CSF and the control group. In the normal menstrual cycle, serum G-CSF concentrations are lowest in the follicular phase, higher in the luteal phase, and highest in the middle of ovulation A retrospective case study was conducted to investigate whether the administration of G-CSF during the superovulation initiation day of ART cycle improved the number of eggs obtained and embryonic development in patients with poor ovarian reserve, with a view to improving future clinical pregnancy rates and live birth rates. We also conducted a retrospective propensity score for the test group (G-CSF group) and the control group (non-G-CSF group), and conducted a statistical analysis of the two groups again. During the period from January 1, 2022 to December 31, 2022, patients receiving ART treatment in the Second Hospital of Lanzhou University; The cases met the inclusion criteria. They were divided into test group(40 patients )and control group (134 patients ) according to whether G-CSF was given on ART superovulation initiation day. The test group and control group were matched according to female age, AMH, bFSH, infertility years, ART, BMI, bLH, PRL, E2, T, TSH, FT3, FT4, fasting blood glucose, fasting islet and whether to use growth hormone .We conducted a statistical analysis after pairing(1:1/1:2)(33 patients:33 patients /31patients:52 patients), to determine whether the treatment of the test group can improve the number of eggs obtained and the high-quality embryo of patients with low ovarian reserve after excluding confounding and non-random factors༈Fig. 1 shows༉. To more clearly identify improvements in ovarian reserve associated with G-CSF, we limited our study to patients with decreased ovarian reserve. We chose serum AMH concentrations below 2 ng/mL as the inclusion criteria for our study because 93% of infertile women in their 40s had serum AMH concentrations below 2 ng/mL [ 3 ]A median serum AMH concentration of 1.9 ng/mL has been studied in 38-year-old Japanese women without children, a population that is on the verge of a dramatic decline in fertility [ 4 ] Participants Inclusion criteria Participants satisfying the following inclusion criteria will be enrolled: Age between 20 and 45 years; No more than 1 prior oocyte retrieval attempt; Serum AMH concentration was lower than 2 ng/mL; Basal serum FSH concentration is greater than or equal to 10 IU/L, All enrolled patients were treated with hyper progesterone hyperovulation (PPOS) regimen; No history of severe allergic disease, severe liver, kidney, or heart disease. All enrolled patients received routine ART assisted pregnancy therapy. willingness to participate in the study and provide written informed consent. On the initiation day of the IVF/ICSI cycle, the test group was given subcutaneous injection of G-CSF (125ug Telzin, Tebao Biological Engineering, Fujian, China) every other day until the day of egg retrieval. Placebo was not used in the control group. Exclusion criteria If one or more of the following criteria is met, patients will be excluded from the study: contraindications to IVF/ICSI treatment (① Either male or female has a severe mental illness, acute infection of the genitourinary system, sexually transmitted diseases ; ② Patients with genetic diseases that are not suitable for fertility under the ' Maternal and Child Health Law ' and are currently unable to carry out pre-implantation genetic diagnosis ; ③ Any party has serious bad habits such as drug abuse ; ④ Any party is exposed to a teratogenic dose of radiation, poisons, or drugs and is in a period of action ; ⑤ The woman's uterus does not have pregnancy function or physical severe disease and can not bear pregnancy. ) contraindications to G-CSF (sickle cell anemia, upper respiratory tract infection, pneumonia, chronic neutropenia, autoimmune thrombocytopenic purpura) and dydrogesterone; inability to fully comply with the study protocol due to other medical conditions. In the past three months, G-CSF has been used for treatment Both groups of patients were treated with IVF/ICSI. Fresh embryo transfer could not be performed due to PPOS protocol, and transplantable embryos were cryopreserved. The number of eggs retrievals and the number of transplantable embryos in one IVF/ICSI cycle were compared as the main outcome measures between the two groups. The number of 2PN, number of optimal embryos, total fertilization and cleavage numbers between the groups were compared as secondary indicates. We can then confirm the number of eggs retrievals, the number of 2PN and the number of D3 transferable embryos from the embryo laboratory records. All the participants who will be assigned to the control group will receive only conventional clinical treatments. With the exception of G-CSF, the intervention and control groups will undergo the same procedures throughout the study. This study analyzed the patients with low ovarian response who underwent ART in the second Hospital of LAN University from January to December 2022, and divided them into test group and control group according to whether G-CSF was given on the initiation day. All patients had informed consent. The study was approved by the Ethics Committee of the Second Hospital of Lanzhou University(2022A-249). Serum concentrations of AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (E2), prolactin (PRL), testosterone (T), thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured by enzyme chemiluminescence immunoassay before study entry. The sensitivity of AMH was 0.01 ng/mL (1.4%, 0.8%), FSH was 0.06 IU/L (2.3%, 1.0%), LH was 0.11 IU/L (6.6%, 3.4%), and E2 was 5.0 pg/mL (0.7%). The PRL sensitivity was 0.10 ng/mL (1.2%, 1.4%), and the T sensitivity was 0.03 ng/mL (2.5%, 3.9%). Assisted reproductive technology Oocytes were collected vaginally 35.5–36 hours after hCG was administered and fertilized as described earlier ,When the male partner is severely infertile (sperm count < 5 × 106 / mL and/or exercise < 20%). The oocyte is considered fertilized when 2 prokaryotes are observed 17 to 19 hours after fertilization or ICSI. Since fresh embryo transfer is not possible with PPOS, transplantable embryos are frozen 3 days after egg retrieval. After IVF/ICSI, the embryos were cultured for 3 days to the D3 embryos stage and cryopreserved by vitrification. All participants will then undergo IVF treatment per local protocols, with agreed on standards. Both groups were treated with IVF/ICSI, followed by PPOS superovulation regimen. Since fresh embryos cannot be transferred by PPOS, transferable embryos need to be cryopreserved. Test group: G-CSF was given during superovulation until the day of egg retrieval. Control group: No placebo was given. Controlled ovarian stimulation will be performed based on female serum hormone levels, age, and body mass index (BMI). Gonadotrophin stimulation with recombinant human follicle stimulating hormone and menotropin (supplying75 IU FSH and 75 IU LH activity per vial) will be started at a daily dose depending on patient characteristics including age, early follicular phase FSH, AMH, antral follicle count and BMI. Dydrogesterone will be administered orally two pills daily from days 1–3 of menstruation to 10 days after ovum retrieval. Transvaginal ultrasonography to assess follicle growth and detect serum estradiol, Progesterone Prog (P), luteinizing hormone, and follicle-stimulating hormone (FSH) levels will be performed throughout the controlled ovarian stimulation cycle. When at least two leading follicles reach 18 mm in diameter, 6,500–10,000 IU of recombinant human chorionic growth factor and (or) triptorelin 0.2mg will be injected, followed by transvaginal ultrasound–guided ovum pick-up 35.5–36 hours later. After 3 days of in vitro culture, we will be able to determine the number of D3 high-quality embryos and freeze all transferable embryos. Embryo cord (Istanbul embryo scoring criteria, 2011) [ 5 ] Embryo quality will be evaluated according to blastomere homogeneity, morphology, cytoplasm uniformity, granulation, vacuolation, and the amount of debris in the embryo. The third day embryos will be divided into four grades. Grade I: blastomeres of equal size, regular morphology, uniform and clear cytoplasm, no granular phenomenon, no fragmentation, or less than 10%. Grade II: blastomeres are slightly different, the morphology is not regular, the cytoplasm may have granular phenomenon, and debris 10–20%. Grade III: The blastomeres are uneven in size and irregular in shape, and the cytoplasm may have an obvious granular phenomenon, with fragments of 20–50%. Grade IV: The size of blastomeres is seriously uneven, and the cytoplasm may have a serious particle phenomenon; fragmentation is > 50%. Normal fertilized embryos on day 3 were divided into 6–9 cells, Grade I and Grade II were good quality embryos. Embryos with a cell count of less than 6 cells or grades III and IV were considered as non-high-quality embryos. Statistical analysis Statistical analysis was performed using Statistics Analysis System(SAS)Version 9.4(NORTH CAROLINA,USA).The normality is tested by the Schapiro-Wilk test and Levene’s test. If the data are subject to normal analysis and the variance is homogeneous, independent sample t tests are performed as appropriate. If the data follow the normal distribution but do not satisfy the homogeneity of variance, the Mann-Whitney U test or the T ' test are performed; If the normal distribution is not followed, the Mann-Whitney U test is performed. P -value below 0.05 is considered significant. Where appropriate, results are expressed as mean ± standard deviation (SD) and median (Q1, Q3). The test group and control group were matched according to female age, AMH, bFSH, infertility years, ART, BMI, bLH, PRL, E2, T, TSH, FT3, FT4, fasting blood glucose, fasting islet and Whether to use growth hormone. After calculating propensity scores, the nearest neighbor technique was used to match women with similar scores in the treatment group (G-CSF group) and the control group (the non-medication group). After estimating propensity scores, patients could be included and matched 1:1/1:2 for a total of 33:33/31:52 pairs. To assess whether the administration of G-CSF improved egg retrievals and embryo quality, the greedy and nearest neighbor matching algorithm was used on the logarithm of the propensity score, and the greedy and nearest neighbor matching algorithm with a caliper distance equal to 0.35 /0.25was used for 1:1/1:2 non-replacement matching between the G-CSF and non-G-CSF patients. To assess matching effect: 1. Based on the 1:1 matching of all variables, the standard deviation of other indicators except TSH is no more than 0.2; 2. The standard deviation of all indicators does not more than 0.25; 3. Based on all variables of 1:2, all indicators of the standard deviation are not more than 0.25. Therefore, the matching effect is considered acceptable by statistics. Results No biased score matching was performed Baseline characteristics of patients Prior to propensity matching, there was no significant difference between the two groups in the baseline characteristics of completed studies, except for AMH and PRL (Table 1 shows). Table 1 Unmatched baseline characteristic sand end-outcome characteristic test group(N = 40) control group(N = 113) total(N = 153) p value Age(years) 31.1 ± 4.69 32.3 ± 5.21 32.0 ± 5.09 0.15 AMH (ng/ml) 2.115 ± 2.0996 1.253 ± 0.5596 1.480 ± 1.2304 0* FSH(IU/L) 7.039 ± 2.0448 8.266 ± 4.4540 7.943 ± 3.9946 0.079 Infertility years 3.86 ± 2.367 3.77 ± 2.651 3.79 ± 2.572 0.612 ART frequency a 1.1 ± 0.38 1.0 ± 0.16 1.0 ± 0.22 0.438 BMI (kg/m2) b 22.910 ± 2.5417 22.250 ± 2.4385 22.422 ± 2.4746 0.146 LH (mIU/ml) 5.256 ± 3.3552 4.325 ± 2.3609 4.570 ± 2.6784 0.2 PRL (ng/ml) 19.475 ± 8.4940 15.770 ± 8.3671 16.747 ± 8.5304 0.008* E2(pg/ml) 52.431 ± 37.724 48.671 ± 30.1345 49.654 ± 32.2026 0.917 T(ng/dl) 28.654 ± 49.5403 24.860 ± 16.1523 25.853 ± 28.7244 0.215 P(ng/ml) 0.763 ± 2.9401 1.006 ± 2.9713 0.943 ± 2.9555 0.06 TSH 2.9226 ± 1.4293 2.8499 ± 1.5024 2.8689 ± 1.4806 0.797 FT3 5.089 ± 0.5737 5.168 ± 0.5974 5.147 ± 0.5904 0.753 FT4 16.091 ± 1.9005 15.655 ± 2.8522 15.770 ± 2.6363 0.288 FBG 5.128 ± 0.5254 4.988 ± 0.4246 5.024 ± 0.4551 0.099 FINS 11.366 ± 5.8391 10.552 ± 4.6031 10.774 ± 4.9604 0.934 Use of growth hormone 9 ± 22.5 18 ± 15.9 27 ± 17.6 0.349 End outcome MII c 5.3 ± 5.07 5.9 ± 3.22 5.8 ± 3.77 0.129 2PN d 6.4 ± 3.74 4.3 ± 2.44 4.8 ± 2.95 0.001* Number of eggs retrieved 8.3 ± 4.16 6.0 ± 3.26 6.6 ± 3.64 0.003* Total fertilization e 7.1 ± 3.69 4.8 ± 2.54 5.4 ± 3.05 0* Optimal embryo number 2.2 ± 2.16 2.1 ± 1.77 2.1 ± 1.87 0.986 Number of transferable embryos 6.6 ± 3.74 4.3 ± 2.39 4.9 ± 2.97 0* Cleavage number f 7.1 ± 3.75 4.6 ± 2.44 5.2 ± 3.02 0* LH, PRL, E2, T, P, TSH, FT3, FT4 were the basic hormone levels of menstrual period *: P <0.05 indicates a statistical difference a: Only patients with one ART were selected b: BMI, the body mass index, is calculated by dividing weight in kilograms by the square of height in meters c: MII Egg, mature egg d: 2PN, embryo with 2 pronucleus e: A sequence of biological processes initiated by entry of a spermatozoon into a mature oocyte followed by formation of the pronuclei. f: Embryos beginning with the 2-cell stage and up to, but not including, the morula stage. Propensity score matching (1:1/1:2) After the propensity score matching (1:1/1:2), the matching indicators were: female age, AMH, bFSH, infertility years, ART, BMI, bLH, PRL, E2, T, TSH, FT3, FT4, fasting blood glucose, fasting islet, and whether or not growth hormone was used. There were no significant differences in female age, bFSH, infertility years, ART number, BMI, bLH, E2, T, P, TSH, FT3, FT4, fasting blood glucose, fasting islets and Whether to use growth hormone between 33/31 G-CSF patients vs 33/52 control patients (Chi-square test or Fisher precision test) (Table 2 shows). Table 2 The 1:1/1:2 propensity score matched of all baseline characteristics 1:1 match of all baseline metrics 1:2match of all baseline metrics characteristics test group (N = 33) control group (N = 33) Total (N = 66) p value Test group (N = 31) control group (N = 52) Total (N = 83) p value Age(years) 31.3 ± 4.88 31.4 ± 4.51 31.3 ± 4.67 0.979 31.5 ± 5.06 31.5 ± 5.13 31.5 ± 5.07 0.989 AMH (ng/ml) 1.629 ± 0.7134 1.550 ± 0.6026 1.590 ± 0.6564 0.43 1.642 ± 0.7040 1.492 ± 0.5608 1.548 ± 0.6182 0.212 FSH(IU/L) 7.145 ± 2.1693 7.412 ± 2.0780 7.278 ± 2.1120 0.599 7.327 ± 2.2206 7.220 ± 2.3713 7.260 ± 2.3030 0.891 Infertility years 3.83 ± 2.515 3.61 ± 2.594 3.72 ± 2.538 0.605 3.95 ± 2.511 3.72 ± 2.531 3.81 ± 2.511 0.625 ART frequency 1.1 ± 0.41 1.0 ± 0.00 1.0 ± 0.27 0.263 1.1 ± 0.42 1.0 ± 0.14 1.0 ± 0.26 0.571 BMI (kg/m2) 22.982 ± 2.4248 22.870 ± 2.4854 22.926 ± 2.4369 0.854 22.373 ± 2.0729 22.715 ± 2.7345 22.587 ± 2.5001 0.756 LH (mIU/ml) 4.855 ± 3.2933 4.504 ± 2.1560 4.679 ± 2.7675 0.878 4.925 ± 3.1648 4.194 ± 1.9618 4.467 ± 2.4869 0.559 PRL (ng/ml) 19.106 ± 7.5848 19.302 ± 9.6153 19.204 ± 8.593 0.654 19.905 ± 8.3682 18.012 ± 9.1877 18.719 ± 8.8864 0.2 E2(pg/ml) 53.835 ± 41.3772 46.144 ± 25.3173 49.990 ± 34.2554 0.964 50.405 ± 33.4409 46.728 ± 28.8381 48.102 ± 30.4889 0.992 T(ng/dl) 27.876 ± 53.7805 20.656 ± 14.2491 24.266 ± 39.2060 0.908 19.032 ± 11.8128 23.846 ± 15.9576 22.048 ± 14.6601 0.165 P(ng/ml) 0.855 ± 3.2374 0.990 ± 3.4314 0.922 ± 3.3107 0.501 0.875 ± 3.3419 0.779 ± 2.7394 0.815 ± 2.9590 0.307 TSH 2.9008 ± 1.5300 3.2528 ± 1.6168 3.0768 ± 1.5719 0.276 2.9881 ± 1.5285 2.8917 ± 1.5666 2.9277 ± 1.5438 0.906 FT3 5.137 ± 0.5618 5.032 ± 0.4622 5.084 ± 0.5132 0.409 5.094 ± 0.5722 5.204 ± 0.6621 5.163 ± 0.6287 0.686 FT4 16.093 ± 2.0120 16.262 ± 2.4928 16.178 ± 2.2493 0.763 15.914 ± 2.0046 16.149 ± 2.6982 16.061 ± 2.4518 0.675 FBG 5.122 ± 0.5463 5.020 ± 0.4506 5.071 ± 0.4995 0.32 5.064 ± 0.4769 5.029 ± 0.5324 5.042 ± 0.4470 0.734 FINS 11.359 ± 5.5139 10.456 ± 3.9340 10.900 ± 4.7582 0.897 10.856 ± 4.9691 11.034 ± 4.7394 10.968 ± 4.7930 0.706 Use of growth hormone 6 ± 18.2 3 ± 9.1 9 ± 13.6 0.282 6 ± 19.4 6 ± 11.5 12 ± 14.5 0.327 Follicular growth, fertilization and embryonic development(End outcomes) No biased score matching was performed 174 ART patients were included and divided into G-CSF group (40 patients) or control group (134 patients) according to whether G-CSF was used during hyperovulation. All G-CSF patients completed one cycle of IVF/ICSI. No adverse reactions were observed during the administration of G-CSF. There were statistically significant differences in number of 2PN(6.4 ± 3.74 vs 4.3 ± 2.44, P = 0.001), number of eggs retrievals(8.3 ± 4.16 vs 6.0 ± 3.26, P = 0.003), number of total fertilization(7.1 ± 3.69 vs 4.8 ± 2.54, P = 0), number of transferable embryos(6.6 ± 3.74 vs 4.3 ± 2.39, P = 0) and number of cleavage(7.1 ± 3.75 vs 4.6 ± 2.44, P = 0) were significantly improved by priming (Table 1 shows). Propensity score matching (1:1/1:2) After the propensity score matching(1:1),There were statistically significant differences in number of MII (4.9 ± 5.15 vs 6.4 ± 2.77 P = 0).The number of 2PN (5.9 ± 3.55 vs 6 ± 2.22, P = 0.1), number of eggs retrievals(7.9 ± 4.17 vs 6.6 ± 2.77, P = 0.3), number of total fertilization(6.9 ± 3.57 vs 5.3 ± 2.39, P = 0.1), number of transferable embryos(6.3 ± 3.58 vs 4.8 ± 1.92, P = 0.1) and number of cleavage(6.8 ± 3.64 vs 5.1 ± 2.24, P = 0.1) tended to be higher in 33 G-CSF patients than in 33 controls, although statistical significance was not attained respectively(Table 3 shows). Table 3 The 1:1/1:2 propensity score matched the end point outcome 1:1 match of all end point efficacy index 1:2 match of all end point efficacy index characteristics test group (N = 33) control group (N = 33) Total (N = 66) p value test group (N = 31) control group (N = 52) Total (N = 83) p value MII 4.9 ± 5.15 6.4 ± 2.77 5.6 ± 4.15 0* 5.3 ± 5.23 6.7 ± 3.67 6.2 ± 4.33 0.055 2PN 5.9 ± 3.55 4.6 ± 2.22 5.3 ± 3.00 0.1 5.9 ± 3.60 4.8 ± 2.77 5.2 ± 3.12 0.17 Number of eggs retrievals 7.9 ± 4.17 6.6 ± 2.77 7.2 ± 3.57 0.3 8.0 ± 4.30 6.9 ± 3.64 7.3 ± 3.91 0.285 Total fertilization 6.9 ± 3.57 5.3 ± 2.39 6.1 ± 3.11 0.1 6.9 ± 3.64 5.5 ± 2.84 6.0 ± 3.20 0.087 Optimal embryo number 2.1 ± 1.77 2.3 ± 1.53 2.2 ± 1.64 0.5 2.0 ± 1.74 2.3 ± 2.03 2.2 ± 1.92 0.577 Number of transferable embryos 6.3 ± 3.58 4.8 ± 1.92 5.5 ± 2.95 0.1 6.4 ± 3.62 4.8 ± 2.49 5.4 ± 3.03 0.045* Cleavage number 6.8 ± 3.64 5.1 ± 2.24 5.9 ± 3.11 0.1 6.8 ± 3.71 5.3 ± 2.73 5.8 ± 3.19 0.08 *: P <0.05 indicates a statistical difference After matching propensity scores(1:2), there were statistically significant differences in number of transferable embryos(6.4 ± 3.62 vs 4.8 ± 2.49, P = 0.045), were significantly improved by priming. The number of 2PN (5.9 ± 3.60 vs 4.8 ± 2.77, P = .17), number of eggs retrievals(8.0 ± 4.30 vs 6.9 ± 3.64, P = 0.285), number of total fertilization(6.9 ± 3.64 vs 5.5 ± 2.84, P = 0.087), and number of cleavage(6.8 ± 3.71 vs 5.3 ± 2.73, P = 0.08) tended to be higher in 31 G-CSF patients than in 52 controls, although statistical significance was not attained respectively(Table 3 shows). In addition, the G-CSF patients achieved more cryopreservation of transplantable embryos than the control group. Oocytes and embryos in the G-CSF group had greater developmental potential. The G-CSF group was able to obtain more oocytes than the control group, and they were more likely to develop into fertilized egg cells or day 3 embryos. In summary, before pairing without preference score and after pairing (1:1/1:2), number of eggs retrievals, number of 2PN, total fertilization number and number of cleavages were all higher than those in control group, but the differences were not statistically significant. The number of transferable embryos in G-CSF group were all higher than those in control group, and the differences were statistically significant. Because the increase in the number of transplantable embryos will increase the number of frozen embryos in patients, thereby increasing the number of poor ovarian reserve patients to thaw the embryo transfer, increasing the pregnancy rate and live birth rate of patients. Discussion This study provides a novel, simple and safe treatment for patients with decreased ovarian reserve. In these patients, the administration of G-CSF on superovulation initiation day significantly improved egg, fertilization, and embryo development obtained by IVF/ICSI, increased the number of transplantable embryos, and thus improved clinical pregnancy and live birth rates after FET in the future. G-CSF administration on initiation day also significantly improved follicular development. This mechanism is significantly different from the previously proposed mechanism by which G-CSF improves implantation and thickens the endometrium. The reproductive clinical effects of G-CSF have been reported. G-CSF has been found to increase implantation rates and clinical pregnancy in ART patients with repeated implantation failure or thinning of the endometrium [ 6 – 10 ]. Previous studies have shown that G-CSF reduces the rate of miscarriage and increases the rate of live birth in women with unexplained recurrent miscarriage [ 11 ], G-CSF has shown high effectiveness in overcoming repeated implantation failures [ 12 ], In women with thinning endometrium, intrauterine administration of G-CSF was found to increase endometrial thickness [ 13 – 15 ]. G-CSF also helps treat some forms of ovarian dysfunction. During the treatment of infertility patients with luteal unruptured follicle syndrome with hCG, administration of G-CSF at the late stage of the follicle was found to aid ovulation and prevent the occurrence of unruptured follicle syndrome (LUFS) [ 16 ] In summary, G-CSF (subcutaneous injection/ uterine perfusion) may improve endometrial receptivity through immune interaction and promoting endometrial growth. It has been reported that G-CSF action occurs rapidly and affects the administration cycle of G-CSF. We found that G-CSF administration on superovulation initiation day showed novel effects on egg and embryo development during the ART cycle. Improved egg and embryonic development in the G-CSF group is a potential mechanism. In animal studies, G-CSF mitigated ovarian follicular degeneration in experimental diabetic rats [ 1 ], G-CSF also increased the number of primary, primary, secondary, and tertiary ovarian follicles in cisplatin treated female rats [ 2 ], In male mice with acute myeloid leukemia treated with chemotherapy drugs, G-CSF restored impaired spermatogenesis and fertility [ 17 ] In other experiments, administration of G-CSF counterbalanced apoptosis [ 18 – 20 ] inflammatory states [ 12 , 17 , 20 ], vascular damage [ 20 , 21 ], growth failure [ 20 , 22 ], and oxidative stress [ 12 , 20 ]. The restoration of this physiological state may suggest a mechanism applicable to enhancing precaval follicle growth in patients with poor ovarian reserve. The autocrine or paracrine role of G-CSF in follicle formation may be involved, as embryos produced by eggs in follicles with higher levels of G-CSF have been reported to be more prone to embryos’ implantation [ 23 ] G-CSF has been shown to promote the export of bone marrow stem cells (BMSC) to peripheral blood and may aid in tissue regeneration[ 24 ] Ovarian transplantation with autologous bone marrow mesenchymal stem cells after 5 days of daily administration of G-CSF improved follicle and oocyte counts, resulting in pregnancy in patients with poor response to antiretroviral therapy[ 25 ] A different but related approach was used in an animal study where human plasma derived from plasma enriched with bone marrow mesenchymal stem cell (PRP) secretory factor after daily administration of G-CSF for 5 days improved follicular development and fertility in a mouse model of chemotherapy-induced ovarian injury[ 26 ]. Similarly, human umbilical cord mesenchymal stem cell-derived conditioned medium (hUCMSC-CM) was found to reduce apoptosis of granulosa cells and depletion of primordium follicles in cisplatin treated mice [ 27 ]. These effects are mediated by G-CSF in a paracrine manner, including increased production of G-CSF by granulosa cells and inhibition of apoptosis via the G-CSF/PI3K/Akt pathway [ 27 ] The clinical safety and tolerability of G-CSF therapy has been demonstrated in the use of healthy bone marrow donors for 3–5 days [ 22 ] patients with severe chronic neutropenia treated daily or every other day for up to 12 years [ 28 ] and patients with ischemic stroke [ 20 ] In healthy bone marrow donors and unexplained repeated miscarriages, patients with repeated implantation failures, chemotherapy, or severe chronic neutropenia, G-CSF administration during pregnancy (daily to every 3 days during 1 to 3 months of gestation) did not result in major maternal or fetal/neonatal adverse events, including teratogenicity [ 10 , 11 , 22 , 28 , 29 ] In our study, there were no adverse events in our subjects. In the future, we will continue to observe the clinical pregnancy rate and live birth rate of patients in the trial group after FET, as well as the safety of babies born. In the future, we can compare the experimental group with the control group to observe congenital abnormalities and weight differences between all the infants treated with G-CSF and the control group. In the normal menstrual cycle, serum G-CSF concentrations are lowest in the follicular phase, higher in the luteal phase, and highest in the middle of ovulation [ 30 ]. The mode and optimal timing of G-CSF administration in the ovarian cycle remain to be determined by further studies. Conclusion In patients with poor ovarian reserve, administration of G-CSF on ART initiation day significantly improved egg, fertilization, and embryonic development on ART. Therefore, the implantation rate, clinical pregnancy rate and live birth rate of FET will increase significantly. G-CSF administration on initiation day enhances egg growth and embryonic development by a different mechanism than the one previously proposed for G-CSF to improve implantation. G-CSF initiation showed no adverse events in our subjects. In the future, we will continue to observe that all infants treated with G-CSF have no congenital abnormalities, their weight, number of weeks of birth, and Apgar score. This study proposes a novel, simple and safe treatment method for poor ovarian reserve. However, since this study is a retrospective clinical study, there will be many confounding factors, and a large-scale, multicenter randomized, double-blind clinical study is needed for further proof. Abbreviations AMH anti-Müllerian hormone ART assisted reproductive technology BMSC bone marrow stem cells CI confidence interval ET embryo transfer E2 17b-estradiol GnRH gonadotropin-releasing hormone FSH follicle-stimulating hormone FT3 free thyronine FT4 free thyroxine G-CSF granulocyte colony-stimulating factor hCG human chorionic gonadotropin hMG human menopausal gonadotropin ICSI intracytoplasmic sperm injection IVF in vitro fertilization LH luteinizing hormone OPU oocyte pick-up OS ovarian stimulation PRP platelet-rich plasma PRL prolactin RR relative risk SD standard deviation T testosterone TSH thyroid-stimulating hormone. Declarations Ethics approval and consent to participate Assisted reproductive technology patients will be screened according to the standard pregnancy. The purpose, procedures, and risks and benefits of the study will be explained to potential participants. After consultation with these potential participants and screening of their clinical information, the reproductive doctor in these hospitals will inform patients whether they are eligible for the study. Written informed consent will be acquired immediately after screening by the investigators. The study protocol and informed consent form have been approved by Lanzhou University Second Hospital, Lanzhou, China and registered at www.clinicaltrials.gov (ChiCTR2200062412). Consent for publication Not applicable Availability of data and materials All data generated or analysed during this study are included in this published article (and its supplementary information files) Competing interests The authors declare that they have no competing interests Funding The trial whose analysis plan was described herein and the authors’ time spent preparing this manuscript have been funded by Lanzhou (Gansu, China) via Support Fund, which receives funds from "A real world study of repeated pregnancy loss in China". The funders played no role in preparing this manuscript. Authors’ contributions ZENG is the first author. ZENG contributed to the analytical plan, and wrote the first draft. and LIANG and ZENG are contributed equally. WANG is the corresponding author. WANG involved in the study design, and led the analytical plan. WANG and LIANG contributed to the critical revision of the manuscript for important intellectual content. All authors have read and approved the final manuscript. and received a donation for the trial. The funders played no role in preparing this manuscript. Acknowledgements Not applicable References Pala HG, Pala EE, Ulkumen BA, Aktug H, Yavasoglu A, Korkmaz HA, et al. The protective effect of granulocyte colony-stimulating factor on endometrium and ovary in a rat model of diabetes mellitus. Page 18/22 Gynecol Obstet Invest. 2014; 78:94–100. doi: 10.1159/000363239 . Akdemir A, Zeybek B, Akman L, Ergenoglu AM, Yeniel AO, Erbas O, et al. Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model. J Gynecol Oncol. 2014; 25:328–33. http://dx.doi.org/10.3802/jgo.2014.25.4.328. . Seifer DB, Baker VL, Leader B. Age-specific serum anti-Müllerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril. 2011; 95:747–50. Doi: 10.1016/j.fertnstert.2010.10. 011. . Segawa T, Omi K, Watanabe Y, Sone Y, Handa M, Kuroda M, et al. Age-specic values of access anti-Müllerian hormone immunoassay carried out on Japanese patients with infertility: a retrospective large-scale study. BMC Women’s Health. 2019; 19:57. https://doi.org/10.1186/s12905-019-0752-z . Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Repro 2011;26(6):1270-83.: Würfel W. Approaches to better implantation. J Ass Reprod Genet. 2000; 17:473. Aleyasin A, Abediasl Z, Nazari A, Sheikh M. Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial. Reproduction. 2016; 151:637–42. Kamath MS, Chittawar PB, Kirubakaran R, Mascarenhas M. Use of granulocyte-colony stimulating factor in assisted reproductive technology: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2017; 214:16–24. http://dx.doi.org/10.1016/j.ejogrb.2017.04.022 . Zhang L, Xu W, Fu X, Huang Q, Guo X, Zhang L, et al. Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta-analysis. Arch Gynecol Obstet. 2018; 298:861–71. https://doi.org/10.1007/s00404-018-4892-4 . Kamath MS, Kirubakaran R, Sunkara SK. Granulocyte-colony stimulating factor administration for subfertile women undergoing assisted reproduction. Cochrane Database Systematic Reviews. 2020;1:CD013226. Doi: 10.1002/14651858.CD013226.pub2 . Scarpellini F, Sbracia M. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. Hum Reprod. 2009; 24:2703–8. Würfel W, Santjohanser C, Hirv K, Bühl M, Meri O, Laubert I, et al. High pregnancy rates with administration of granulocyte colony-stimulating factor in ART-patients with repetitive implantation failure and lacking killer-cell immunoglobulin-like receptors. Hum Reprod. 2010; 25:2151–3. Gleicher N, Vidali A, Barad DH. Successful treatment of unresponsive thin endometrium. Fertil Steril.2011;95: 2123.e13-e17. Gleicher N, Kim A, Michaeli T, Lee H, Shohat-Tal A, Lazzaroni E, et al. A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies. Hum Reprod. 2013; 28:172–7. doi: 10.1093/humrep/des370 . Xie Y, Zhang T, Tian Z, Zhang J, Wang W, Zhang H, et al. Efficacy of intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) for infertile women with thin endometrium: a systematic review and meta-analysis. Am J Reprod Immunol. 2017;78: e12701 .https://doi.org/10.1111/aji.12701 Shibata T, Makinoda S, Waseda T, Tomizawa H, Fujii R, Utsunomiya T. Granulocyte colony stimulating factor as a potential inducer of ovulation in infertile women with luteinized unruptured follicle syndrome. Translational Res. 2016; 171:63–70. Michailov Y, AbuMadighem A, Lunenfeld E, Kapelushnik J, Huleihel M. Granulocyte colony-stimulating factor restored impaired spermatogenesis and fertility in an AML-chemotherapy mice model. Int J Mol Sci. 2021; 22:11157. https://doi.org/10.3390/ijms222011157 . Kojima H, Otani A, Oishi A, Makiyama Y, Nakagawa S, Yoshimura N. Granulocyte colony-stimulating factor attenuates oxidative stress-induced apoptosis in vascular endothelial cells and exhibits functional and morphologic protective effect in oxygen-induced retinopathy. Blood. 2011; 117:1091–100. doi: 10.1182/blood-2010-05-286963 . Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med. 2005; 11:305–11. doi: 10.1038/nm1199 . Patel AMR, Apaijai N, Chattipakorn N, Chattipakorn SC. The protective and reparative role of colony-stimulating factors in the brain with cerebral ischemia/reperfusion injury. Neuroendocrinology.2021;111:1029–65. doi: 10.1159/000512367 . Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Shinn DI, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res. 2005; 1058:120–8. Würfel W. Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and/or recurrent spontaneous abortions. J Reprod Immunol. 2015; 108:123–35. http://dx.doi.org/10.1016/j.jri.2015.01.010 . Lédée N, Gridelet V, Ravet S, Jouan C, Gaspard O, Wenders F, et al. Impact of follicular G-CSF quantication on subsequent embryo transfer decisions: a proof of concept study. Hum Reprod.2013; 28:406–13. doi: 10.1093/humrep/des354 . de Kruijf EFM, Fibbe WE, van Pel M. Cytokine-induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche. Ann N Y Acad Sci.Page 20/222020;1466:24–38. doi: 10.1111/nyas. 14059. . Herraiz S, Romeu M, Buigues A, Martinez S, Diaz-Garcia C, Gómez-SeguiＩ, et al. Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders. Fertil Steril. 2018; 110:496–505. https://doi.org/10.1016/j.fertnstert.2018.04.025 Buigues A, Marchante M, de Miguel-Gómez L, Martinez J, Cervelló I, Pellicer A, et al. Stem cell-secreted factor therapy regenerates the ovarian niche and rescues follicles. Am J Obstet Gynecol 2021; 225:65. e1-14. https://doi.org/10.1016/j.ajog.2021.01.023. Hong L, Yan L, Xin Z, Hao J, Liu W, Wang S, et al. Protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium on ovarian damage. J Mol Cell Biology.2020; 12:372–85. doi: 10.1093/jmcb/mjz105 . Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, et al. Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hemtol. 2003; 72:82–93. Doi: 10.1002/ajh.10255 Cruz M, Alecsandru D, García-Valasco JA, Requena A. Use of granulocyte colony-stimulating factor in ART treatment does not increase the risk of adverse perinatal outcomes. RBMO. 2019; 39:976–80. https://doi.org/10.1016/j.rbmo.2019.09.0081472-6483 . Makinoda S, Mikuni M, Furuta I, Okuyama K, Sagawa T, Fujimoto S. Serum concentration of endogeneous G-CSF in women during the menstrual cycle and pregnancy. Eur J Clin Invest.1995;25:877–9. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3997062","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":279504505,"identity":"dbe8d40f-04b7-413b-8ec5-4adc7938f7fa","order_by":0,"name":"Xianghui Zeng","email":"","orcid":"","institution":"Lanzhou University Second Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xianghui","middleName":"","lastName":"Zeng","suffix":""},{"id":279504506,"identity":"58402223-eba4-4f54-846e-b6a626ddb9f1","order_by":1,"name":"Zhongzhen Liang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Zhongzhen","middleName":"","lastName":"Liang","suffix":""},{"id":279504507,"identity":"dbf5c177-c2fa-4c97-a143-c36e16fe542a","order_by":2,"name":"Fang Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYLCCChDB3twAohgbiNJyBkTwHCRZi0QikVr4pc8YMBxss8uTj3zY/JmHwUZ2wwHmZw/waZHsywFpSS42vJ3YYMzDkGa84QCbuQE+LQZneAyYP25jTtw4O7EhmYfhcOKGAzxsEvi02AO1MBzcVp+4cebBhsM8DP8JazHgAWs5nDhfgrGxmYfhAGEtEmfYChgO/jueuIEnsZlxjkGy8czDbGZ4tfD3MG9gOHCmOnF+++HDH95U2Mn2HW9+hlcLAwOH+Q+wCw+ASSBmxq8eCNgfgCn5BoIqR8EoGAWjYKQCAEL5S08MhUsPAAAAAElFTkSuQmCC","orcid":"","institution":"Centre for Assisted Reproductive of Lanzhou versity Second Hospital","correspondingAuthor":true,"prefix":"","firstName":"Fang","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-02-28 15:21:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3997062/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3997062/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52792383,"identity":"cf37c0a5-73c2-43b5-9f0f-daf190e2975f","added_by":"auto","created_at":"2024-03-15 20:17:49","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":380837,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of inclusion and statistical analysis\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3997062/v1/d998fba4104f92c9b19c59a9.jpeg"},{"id":59707824,"identity":"3d7af3b7-7f85-4c13-a9e1-aaf1e48d17b5","added_by":"auto","created_at":"2024-07-05 06:18:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1144667,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3997062/v1/8b103d9c-43fa-4f6c-baa4-d8d60489aaa0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Granulocyte colony-stimulating factor priming improves egg and embryo quality in patients with poor ovarian reserve: a retrospective case study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn diabetic rats, G-CSF consistently reduced ovarian follicular degeneration and ovarian stromal degeneration and rupture, while increasing the number of presinus follicles [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] G-CSF also significantly increased periluminal follicles and serum AMH in rats with cisplatin induced ovarian reserve decline [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eConsidering the role of G-CSF in animal models, in 2022 we gave G-CSF to patients with poor ovarian reserve simultaneously during superovulation. We observed that in patients with ART(who were not given G-CSF)during hyperovulation serum G-CSF concentrations were lowest at the follicular stage ,highest on trigger day ,decreased after egg retrieval ,ang were higher in follicular fluid than in serum .In the future, we can compare the experimental group with the control group to observe congenital abnormalities and weight difference between all the infants treated with G-CSF and the control group. In the normal menstrual cycle, serum G-CSF concentrations are lowest in the follicular phase, higher in the luteal phase, and highest in the middle of ovulation\u003c/p\u003e \u003cp\u003eA retrospective case study was conducted to investigate whether the administration of G-CSF during the superovulation initiation day of ART cycle improved the number of eggs obtained and embryonic development in patients with poor ovarian reserve, with a view to improving future clinical pregnancy rates and live birth rates. We also conducted a retrospective propensity score for the test group (G-CSF group) and the control group (non-G-CSF group), and conducted a statistical analysis of the two groups again. During the period from January 1, 2022 to December 31, 2022, patients receiving ART treatment in the Second Hospital of Lanzhou University; The cases met the inclusion criteria. They were divided into test group(40 patients )and control group (134 patients ) according to whether G-CSF was given on ART superovulation initiation day.\u003c/p\u003e \u003cp\u003eThe test group and control group were matched according to female age, AMH, bFSH, infertility years, ART, BMI, bLH, PRL, E2, T, TSH, FT3, FT4, fasting blood glucose, fasting islet and whether to use growth hormone .We conducted a statistical analysis after pairing(1:1/1:2)(33 patients:33 patients /31patients:52 patients), to determine whether the treatment of the test group can improve the number of eggs obtained and the high-quality embryo of patients with low ovarian reserve after excluding confounding and non-random factors༈Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows༉.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo more clearly identify improvements in ovarian reserve associated with G-CSF, we limited our study to patients with decreased ovarian reserve. We chose serum AMH concentrations below 2 ng/mL as the inclusion criteria for our study because 93% of infertile women in their 40s had serum AMH concentrations below 2 ng/mL [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]A median serum AMH concentration of 1.9 ng/mL has been studied in 38-year-old Japanese women without children, a population that is on the verge of a dramatic decline in fertility [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e"},{"header":"Participants","content":"\u003cp\u003eInclusion criteria\u003c/p\u003e \u003cp\u003eParticipants satisfying the following inclusion criteria will be enrolled:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAge between 20 and 45 years;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNo more than 1 prior oocyte retrieval attempt;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSerum AMH concentration was lower than 2 ng/mL; Basal serum FSH concentration is greater than or equal to 10 IU/L, All enrolled patients were treated with hyper progesterone hyperovulation (PPOS) regimen;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNo history of severe allergic disease, severe liver, kidney, or heart disease.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAll enrolled patients received routine ART assisted pregnancy therapy. willingness to participate in the study and provide written informed consent. On the initiation day of the IVF/ICSI cycle, the test group was given subcutaneous injection of G-CSF (125ug Telzin, Tebao Biological Engineering, Fujian, China) every other day until the day of egg retrieval. Placebo was not used in the control group.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eExclusion criteria\u003c/p\u003e \u003cp\u003eIf one or more of the following criteria is met, patients will be excluded from the study:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003econtraindications to IVF/ICSI treatment (① Either male or female has a severe mental illness, acute infection of the genitourinary system, sexually transmitted diseases ; ② Patients with genetic diseases that are not suitable for fertility under the ' Maternal and Child Health Law ' and are currently unable to carry out pre-implantation genetic diagnosis ; ③ Any party has serious bad habits such as drug abuse ; ④ Any party is exposed to a teratogenic dose of radiation, poisons, or drugs and is in a period of action ; ⑤ The woman's uterus does not have pregnancy function or physical severe disease and can not bear pregnancy. )\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003econtraindications to G-CSF (sickle cell anemia, upper respiratory tract infection, pneumonia, chronic neutropenia, autoimmune thrombocytopenic purpura) and dydrogesterone;\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003einability to fully comply with the study protocol due to other medical conditions.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIn the past three months, G-CSF has been used for treatment\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eBoth groups of patients were treated with IVF/ICSI. Fresh embryo transfer could not be performed due to PPOS protocol, and transplantable embryos were cryopreserved. The number of eggs retrievals and the number of transplantable embryos in one IVF/ICSI cycle were compared as the main outcome measures between the two groups. The number of 2PN, number of optimal embryos, total fertilization and cleavage numbers between the groups were compared as secondary indicates.\u003c/p\u003e \u003cp\u003eWe can then confirm the number of eggs retrievals, the number of 2PN and the number of D3 transferable embryos from the embryo laboratory records. All the participants who will be assigned to the control group will receive only conventional clinical treatments. With the exception of G-CSF, the intervention and control groups will undergo the same procedures throughout the study.\u003c/p\u003e \u003cp\u003eThis study analyzed the patients with low ovarian response who underwent ART in the second Hospital of LAN University from January to December 2022, and divided them into test group and control group according to whether G-CSF was given on the initiation day. All patients had informed consent. The study was approved by the Ethics Committee of the Second Hospital of Lanzhou University(2022A-249).\u003c/p\u003e \u003cp\u003eSerum concentrations of AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (E2), prolactin (PRL), testosterone (T), thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured by enzyme chemiluminescence immunoassay before study entry. The sensitivity of AMH was 0.01 ng/mL (1.4%, 0.8%), FSH was 0.06 IU/L (2.3%, 1.0%), LH was 0.11 IU/L (6.6%, 3.4%), and E2 was 5.0 pg/mL (0.7%). The PRL sensitivity was 0.10 ng/mL (1.2%, 1.4%), and the T sensitivity was 0.03 ng/mL (2.5%, 3.9%).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAssisted reproductive technology\u003c/h2\u003e \u003cp\u003eOocytes were collected vaginally 35.5\u0026ndash;36 hours after hCG was administered and fertilized as described earlier ,When the male partner is severely infertile (sperm count \u0026lt; 5 \u0026times; 106 / mL and/or exercise \u0026lt; 20%). The oocyte is considered fertilized when 2 prokaryotes are observed 17 to 19 hours after fertilization or ICSI. Since fresh embryo transfer is not possible with PPOS, transplantable embryos are frozen 3 days after egg retrieval. After IVF/ICSI, the embryos were cultured for 3 days to the D3 embryos stage and cryopreserved by vitrification.\u003c/p\u003e \u003cp\u003e All participants will then undergo IVF treatment per local protocols, with agreed on standards.\u003c/p\u003e \u003cp\u003eBoth groups were treated with IVF/ICSI, followed by PPOS superovulation regimen. Since fresh embryos cannot be transferred by PPOS, transferable embryos need to be cryopreserved. Test group: G-CSF was given during superovulation until the day of egg retrieval. Control group: No placebo was given. Controlled ovarian stimulation will be performed based on female serum hormone levels, age, and body mass index (BMI). Gonadotrophin stimulation with recombinant human follicle stimulating hormone and menotropin (supplying75 IU FSH and 75 IU LH activity per vial) will be started at a daily dose depending on patient characteristics including age, early follicular phase FSH, AMH, antral follicle count and BMI. Dydrogesterone will be administered orally two pills daily from days 1\u0026ndash;3 of menstruation to 10 days after ovum retrieval. Transvaginal ultrasonography to assess follicle growth and detect serum estradiol, Progesterone Prog (P), luteinizing hormone, and follicle-stimulating hormone (FSH) levels will be performed throughout the controlled ovarian stimulation cycle. When at least two leading follicles reach 18 mm in diameter, 6,500\u0026ndash;10,000 IU of recombinant human chorionic growth factor and (or) triptorelin 0.2mg will be injected, followed by transvaginal ultrasound\u0026ndash;guided ovum pick-up 35.5\u0026ndash;36 hours later. After 3 days of in vitro culture, we will be able to determine the number of D3 high-quality embryos and freeze all transferable embryos.\u003c/p\u003e \u003cp\u003eEmbryo cord (Istanbul embryo scoring criteria, 2011) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Embryo quality will be evaluated according to blastomere homogeneity, morphology, cytoplasm uniformity, granulation, vacuolation, and the amount of debris in the embryo.\u003c/p\u003e \u003cp\u003eThe third day embryos will be divided into four grades.\u003c/p\u003e \u003cp\u003eGrade I: blastomeres of equal size, regular morphology, uniform and clear cytoplasm, no granular phenomenon, no fragmentation, or less than 10%.\u003c/p\u003e \u003cp\u003eGrade II: blastomeres are slightly different, the morphology is not regular, the cytoplasm may have granular phenomenon, and debris 10\u0026ndash;20%.\u003c/p\u003e \u003cp\u003eGrade III: The blastomeres are uneven in size and irregular in shape, and the cytoplasm may have an obvious granular phenomenon, with fragments of 20\u0026ndash;50%.\u003c/p\u003e \u003cp\u003eGrade IV: The size of blastomeres is seriously uneven, and the cytoplasm may have a serious particle phenomenon; fragmentation is \u0026gt;\u0026thinsp;50%.\u003c/p\u003e \u003cp\u003eNormal fertilized embryos on day 3 were divided into 6\u0026ndash;9 cells, Grade I and Grade II were good quality embryos. Embryos with a cell count of less than 6 cells or grades III and IV were considered as non-high-quality embryos.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using Statistics Analysis System(SAS)Version 9.4(NORTH CAROLINA,USA).The normality is tested by the Schapiro-Wilk test and Levene\u0026rsquo;s test. If the data are subject to normal analysis and the variance is homogeneous, independent sample t tests are performed as appropriate. If the data follow the normal distribution but do not satisfy the homogeneity of variance, the Mann-Whitney U test or the T ' test are performed; If the normal distribution is not followed, the Mann-Whitney U test is performed. \u003cem\u003eP\u003c/em\u003e-value below 0.05 is considered significant. Where appropriate, results are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and median (Q1, Q3).\u003c/p\u003e \u003cp\u003eThe test group and control group were matched according to female age, AMH, bFSH, infertility years, ART, BMI, bLH, PRL, E2, T, TSH, FT3, FT4, fasting blood glucose, fasting islet and Whether to use growth hormone. After calculating propensity scores, the nearest neighbor technique was used to match women with similar scores in the treatment group (G-CSF group) and the control group (the non-medication group). After estimating propensity scores, patients could be included and matched 1:1/1:2 for a total of 33:33/31:52 pairs.\u003c/p\u003e \u003cp\u003eTo assess whether the administration of G-CSF improved egg retrievals and embryo quality, the greedy and nearest neighbor matching algorithm was used on the logarithm of the propensity score, and the greedy and nearest neighbor matching algorithm with a caliper distance equal to 0.35 /0.25was used for 1:1/1:2 non-replacement matching between the G-CSF and non-G-CSF patients. To assess matching effect: 1. Based on the 1:1 matching of all variables, the standard deviation of other indicators except TSH is no more than 0.2; 2. The standard deviation of all indicators does not more than 0.25; 3. Based on all variables of 1:2, all indicators of the standard deviation are not more than 0.25. Therefore, the matching effect is considered acceptable by statistics.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eNo biased score matching was performed\u003c/h2\u003e \u003cp\u003eBaseline characteristics of patients Prior to propensity matching, there was no significant difference between the two groups in the baseline characteristics of completed studies, except for AMH and PRL (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnmatched baseline characteristic sand end-outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003echaracteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003etest group(N\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003econtrol group(N\u0026thinsp;=\u0026thinsp;113)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003etotal(N\u0026thinsp;=\u0026thinsp;153)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e32.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMH (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.115\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.253\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.480\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH(IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.039\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0448\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.266\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4540\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e7.943\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9946\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfertility years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.86\u0026thinsp;\u0026plusmn;\u0026thinsp;2.367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.651\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.79\u0026thinsp;\u0026plusmn;\u0026thinsp;2.572\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eART frequency \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.438\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e22.910\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5417\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e22.250\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e22.422\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.146\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH (mIU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.256\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3552\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.325\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.570\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6784\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRL (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e19.475\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4940\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.770\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3671\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e16.747\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE2(pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e52.431\u0026thinsp;\u0026plusmn;\u0026thinsp;37.724\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e48.671\u0026thinsp;\u0026plusmn;\u0026thinsp;30.1345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e49.654\u0026thinsp;\u0026plusmn;\u0026thinsp;32.2026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT(ng/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e28.654\u0026thinsp;\u0026plusmn;\u0026thinsp;49.5403\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e24.860\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1523\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e25.853\u0026thinsp;\u0026plusmn;\u0026thinsp;28.7244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP(ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.763\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9401\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.006\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9713\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.943\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.9226\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.8499\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.8689\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4806\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.797\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.089\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.168\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.147\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e16.091\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.655\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e15.770\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFBG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.128\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.988\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.024\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFINS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.366\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.552\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10.774\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.934\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of growth hormone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;22.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;17.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnd outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMII \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2PN \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of eggs retrieved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal fertilization \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptimal embryo number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of transferable embryos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCleavage number \u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLH, PRL, E2, T, P, TSH, FT3, FT4 were the basic hormone levels of menstrual period\u003c/p\u003e \u003cp\u003e*:\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 indicates a statistical difference\u003c/p\u003e \u003cp\u003ea: Only patients with one ART were selected\u003c/p\u003e \u003cp\u003eb: BMI, the body mass index, is calculated by dividing weight in kilograms by the square of height in meters\u003c/p\u003e \u003cp\u003ec: MII Egg, mature egg\u003c/p\u003e \u003cp\u003ed: 2PN, embryo with 2 pronucleus\u003c/p\u003e \u003cp\u003ee: A sequence of biological processes initiated by entry of a spermatozoon into a mature oocyte followed by formation of the pronuclei.\u003c/p\u003e \u003cp\u003ef: Embryos beginning with the 2-cell stage and up to, but not including, the morula stage.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePropensity score matching (1:1/1:2)\u003c/h2\u003e \u003cp\u003eAfter the propensity score matching (1:1/1:2), the matching indicators were: female age, AMH, bFSH, infertility years, ART, BMI, bLH, PRL, E2, T, TSH, FT3, FT4, fasting blood glucose, fasting islet, and whether or not growth hormone was used. There were no significant differences in female age, bFSH, infertility years, ART number, BMI, bLH, E2, T, P, TSH, FT3, FT4, fasting blood glucose, fasting islets and Whether to use growth hormone between 33/31 G-CSF patients vs 33/52 control patients (Chi-square test or Fisher precision test) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe 1:1/1:2 propensity score matched of all baseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e1:1 match of all baseline metrics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003e1:2match of all baseline metrics\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003echaracteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003etest group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003econtrol group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTest group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003econtrol group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMH (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.629\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.550\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.590\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.642\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.492\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5608\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.548\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH(IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.145\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1693\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.412\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.278\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.599\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e 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colname=\"c3\"\u003e \u003cp\u003e46.144\u0026thinsp;\u0026plusmn;\u0026thinsp;25.3173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.990\u0026thinsp;\u0026plusmn;\u0026thinsp;34.2554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50.405\u0026thinsp;\u0026plusmn;\u0026thinsp;33.4409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46.728\u0026thinsp;\u0026plusmn;\u0026thinsp;28.8381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e48.102\u0026thinsp;\u0026plusmn;\u0026thinsp;30.4889\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.992\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT(ng/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.876\u0026thinsp;\u0026plusmn;\u0026thinsp;53.7805\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.656\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2491\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.266\u0026thinsp;\u0026plusmn;\u0026thinsp;39.2060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.908\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19.032\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.846\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e 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colname=\"c3\"\u003e \u003cp\u003e5.032\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4622\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.084\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.094\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5722\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.204\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.163\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6287\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.686\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.093\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.262\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4928\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.178\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.763\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.914\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16.149\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e16.061\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.675\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFBG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.122\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5463\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.020\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.071\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4995\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.064\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4769\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.029\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5324\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.042\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4470\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.734\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFINS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.359\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.456\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9340\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.900\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.856\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.034\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7394\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10.968\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.706\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of growth hormone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;18.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.327\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFollicular growth, fertilization and embryonic development(End outcomes)\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eNo biased score matching was performed\u003c/h2\u003e \u003cp\u003e174 ART patients were included and divided into G-CSF group (40 patients) or control group (134 patients) according to whether G-CSF was used during hyperovulation. All G-CSF patients completed one cycle of IVF/ICSI. No adverse reactions were observed during the administration of G-CSF. There were statistically significant differences in number of 2PN(6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74 vs 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), number of eggs retrievals(8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16 vs 6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), number of total fertilization(7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.69 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0), number of transferable embryos(6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74 vs 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0) and number of cleavage(7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75 vs 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0) were significantly improved by priming (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePropensity score matching (1:1/1:2)\u003c/h2\u003e \u003cp\u003eAfter the propensity score matching(1:1),There were statistically significant differences in number of MII (4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15 vs 6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77 \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0).The number of 2PN (5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.55 vs 6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1), number of eggs retrievals(7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.17 vs 6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.3), number of total fertilization(6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57 vs 5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1), number of transferable embryos(6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.58 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1) and number of cleavage(6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64 vs 5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1) tended to be higher in 33 G-CSF patients than in 33 controls, although statistical significance was not attained respectively(Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe 1:1/1:2 propensity score matched the end point outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e1:1 match of all end point efficacy index\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003e1:2 match of all end point efficacy index\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003echaracteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003etest group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003econtrol group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003etest group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003econtrol group\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2PN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of eggs retrievals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal fertilization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptimal embryo number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.577\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of transferable embryos\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.045*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCleavage number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e*:\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 indicates a statistical difference\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter matching propensity scores(1:2), there were statistically significant differences in number of transferable embryos(6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.62 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045), were significantly improved by priming. The number of 2PN (5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.60 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.17), number of eggs retrievals(8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30 vs 6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.285), number of total fertilization(6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64 vs 5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.087), and number of cleavage(6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71 vs 5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.73,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08) tended to be higher in 31 G-CSF patients than in 52 controls, although statistical significance was not attained respectively(Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows).\u003c/p\u003e \u003cp\u003eIn addition, the G-CSF patients achieved more cryopreservation of transplantable embryos than the control group. Oocytes and embryos in the G-CSF group had greater developmental potential. The G-CSF group was able to obtain more oocytes than the control group, and they were more likely to develop into fertilized egg cells or day 3 embryos.\u003c/p\u003e \u003cp\u003eIn summary, before pairing without preference score and after pairing (1:1/1:2), number of eggs retrievals, number of 2PN, total fertilization number and number of cleavages were all higher than those in control group, but the differences were not statistically significant. The number of transferable embryos in G-CSF group were all higher than those in control group, and the differences were statistically significant. Because the increase in the number of transplantable embryos will increase the number of frozen embryos in patients, thereby increasing the number of poor ovarian reserve patients to thaw the embryo transfer, increasing the pregnancy rate and live birth rate of patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides a novel, simple and safe treatment for patients with decreased ovarian reserve. In these patients, the administration of G-CSF on superovulation initiation day significantly improved egg, fertilization, and embryo development obtained by IVF/ICSI, increased the number of transplantable embryos, and thus improved clinical pregnancy and live birth rates after FET in the future. G-CSF administration on initiation day also significantly improved follicular development. This mechanism is significantly different from the previously proposed mechanism by which G-CSF improves implantation and thickens the endometrium.\u003c/p\u003e \u003cp\u003eThe reproductive clinical effects of G-CSF have been reported. G-CSF has been found to increase implantation rates and clinical pregnancy in ART patients with repeated implantation failure or thinning of the endometrium [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Previous studies have shown that G-CSF reduces the rate of miscarriage and increases the rate of live birth in women with unexplained recurrent miscarriage [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], G-CSF has shown high effectiveness in overcoming repeated implantation failures [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], In women with thinning endometrium, intrauterine administration of G-CSF was found to increase endometrial thickness [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. G-CSF also helps treat some forms of ovarian dysfunction. During the treatment of infertility patients with luteal unruptured follicle syndrome with hCG, administration of G-CSF at the late stage of the follicle was found to aid ovulation and prevent the occurrence of unruptured follicle syndrome (LUFS) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn summary, G-CSF (subcutaneous injection/ uterine perfusion) may improve endometrial receptivity through immune interaction and promoting endometrial growth. It has been reported that G-CSF action occurs rapidly and affects the administration cycle of G-CSF. We found that G-CSF administration on superovulation initiation day showed novel effects on egg and embryo development during the ART cycle. Improved egg and embryonic development in the G-CSF group is a potential mechanism.\u003c/p\u003e \u003cp\u003eIn animal studies, G-CSF mitigated ovarian follicular degeneration in experimental diabetic rats [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], G-CSF also increased the number of primary, primary, secondary, and tertiary ovarian follicles in cisplatin treated female rats [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], In male mice with acute myeloid leukemia treated with chemotherapy drugs, G-CSF restored impaired spermatogenesis and fertility [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn other experiments, administration of G-CSF counterbalanced apoptosis [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] inflammatory states [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], vascular damage [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], growth failure [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and oxidative stress [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The restoration of this physiological state may suggest a mechanism applicable to enhancing precaval follicle growth in patients with poor ovarian reserve. The autocrine or paracrine role of G-CSF in follicle formation may be involved, as embryos produced by eggs in follicles with higher levels of G-CSF have been reported to be more prone to embryos\u0026rsquo; implantation [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eG-CSF has been shown to promote the export of bone marrow stem cells (BMSC) to peripheral blood and may aid in tissue regeneration[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Ovarian transplantation with autologous bone marrow mesenchymal stem cells after 5 days of daily administration of G-CSF improved follicle and oocyte counts, resulting in pregnancy in patients with poor response to antiretroviral therapy[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] A different but related approach was used in an animal study where human plasma derived from plasma enriched with bone marrow mesenchymal stem cell (PRP) secretory factor after daily administration of G-CSF for 5 days improved follicular development and fertility in a mouse model of chemotherapy-induced ovarian injury[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Similarly, human umbilical cord mesenchymal stem cell-derived conditioned medium (hUCMSC-CM) was found to reduce apoptosis of granulosa cells and depletion of primordium follicles in cisplatin treated mice [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. These effects are mediated by G-CSF in a paracrine manner, including increased production of G-CSF by granulosa cells and inhibition of apoptosis via the G-CSF/PI3K/Akt pathway [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe clinical safety and tolerability of G-CSF therapy has been demonstrated in the use of healthy bone marrow donors for 3\u0026ndash;5 days [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] patients with severe chronic neutropenia treated daily or every other day for up to 12 years [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and patients with ischemic stroke [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn healthy bone marrow donors and unexplained repeated miscarriages, patients with repeated implantation failures, chemotherapy, or severe chronic neutropenia, G-CSF administration during pregnancy (daily to every 3 days during 1 to 3 months of gestation) did not result in major maternal or fetal/neonatal adverse events, including teratogenicity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e29\u003c/span\u003e] In our study, there were no adverse events in our subjects. In the future, we will continue to observe the clinical pregnancy rate and live birth rate of patients in the trial group after FET, as well as the safety of babies born. In the future, we can compare the experimental group with the control group to observe congenital abnormalities and weight differences between all the infants treated with G-CSF and the control group. In the normal menstrual cycle, serum G-CSF concentrations are lowest in the follicular phase, higher in the luteal phase, and highest in the middle of ovulation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The mode and optimal timing of G-CSF administration in the ovarian cycle remain to be determined by further studies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn patients with poor ovarian reserve, administration of G-CSF on ART initiation day significantly improved egg, fertilization, and embryonic development on ART. Therefore, the implantation rate, clinical pregnancy rate and live birth rate of FET will increase significantly. G-CSF administration on initiation day enhances egg growth and embryonic development by a different mechanism than the one previously proposed for G-CSF to improve implantation. G-CSF initiation showed no adverse events in our subjects. In the future, we will continue to observe that all infants treated with G-CSF have no congenital abnormalities, their weight, number of weeks of birth, and Apgar score. This study proposes a novel, simple and safe treatment method for poor ovarian reserve. However, since this study is a retrospective clinical study, there will be many confounding factors, and a large-scale, multicenter randomized, double-blind clinical study is needed for further proof.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eanti-M\u0026uuml;llerian hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eassisted reproductive technology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebone marrow stem cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eembryo transfer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eE2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e17b-estradiol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGnRH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egonadotropin-releasing hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efollicle-stimulating hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFT3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efree thyronine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFT4\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efree thyroxine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eG-CSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egranulocyte colony-stimulating factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ehCG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman chorionic gonadotropin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ehMG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman menopausal gonadotropin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICSI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintracytoplasmic sperm injection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ein vitro fertilization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eluteinizing hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOPU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoocyte pick-up\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eovarian stimulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eplatelet-rich plasma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprolactin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erelative risk\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etestosterone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethyroid-stimulating hormone.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAssisted reproductive technology patients will be screened according to the standard pregnancy.\u003c/p\u003e\n\u003cp\u003eThe purpose, procedures, and risks and benefits of the study will be explained to potential participants. After consultation with these potential participants and screening of their clinical information, the reproductive doctor in these hospitals will inform patients whether they are eligible for the study. Written informed consent will be acquired immediately after screening by the investigators.\u003c/p\u003e\n\u003cp\u003eThe study protocol and informed consent form have been approved by Lanzhou University Second Hospital, Lanzhou, China and registered at www.clinicaltrials.gov (ChiCTR2200062412).\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\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article (and its supplementary information files)\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\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;trial whose analysis plan was\u0026nbsp;described herein and the authors\u0026rsquo; time spent preparing\u0026nbsp;this manuscript have been funded by Lanzhou (Gansu, China) via Support Fund, which receives funds from \u0026quot;A real world study of repeated pregnancy loss in China\u0026quot;. The funders played no\u0026nbsp;role in preparing this\u0026nbsp;manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ZENG is the first author. ZENG contributed to the analytical plan, and wrote the first draft. and LIANG and ZENG are contributed equally. WANG is the corresponding author. WANG involved in the study design, and led the analytical plan. WANG and LIANG contributed to the critical revision of the manuscript for important intellectual content. All authors have read and approved the final manuscript. and received a donation for the trial. The funders played no role in preparing this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePala HG, Pala EE, Ulkumen BA, Aktug H, Yavasoglu A, Korkmaz HA, et al. The protective effect of granulocyte colony-stimulating factor on endometrium and ovary in a rat model of diabetes mellitus. Page 18/22 Gynecol Obstet Invest. 2014; 78:94\u0026ndash;100. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000363239\u003c/span\u003e\u003cspan address=\"10.1159/000363239\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkdemir A, Zeybek B, Akman L, Ergenoglu AM, Yeniel AO, Erbas O, et al. 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Use of granulocyte colony-stimulating factor in ART treatment does not increase the risk of adverse perinatal outcomes. RBMO. 2019; 39:976\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.rbmo.2019.09.0081472-6483\u003c/span\u003e\u003cspan address=\"10.1016/j.rbmo.2019.09.0081472-6483\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakinoda S, Mikuni M, Furuta I, Okuyama K, Sagawa T, Fujimoto S. Serum concentration of endogeneous G-CSF in women during the menstrual cycle and pregnancy. Eur J Clin Invest.1995;25:877\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\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":"Granulocyte colony-stimulating factor, poor ovarian response, number of transferable embryos, number of eggs retrievals, propensity score matching","lastPublishedDoi":"10.21203/rs.3.rs-3997062/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3997062/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGranulocyte colony-stimulating factor (G-CSF) administration increased ovarian preantral follicles in animal models with diminished ovarian reserve. We retrospectively investigated whether G-CSF priming on superovulation initiation day with assisted reproductive technology (ART) improved egg maturation and embryonic development in patients with poor ovarian reserve.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this retrospective clinical case study, 174 patients aged 20 to 45 years were divided into a test group(40 patients each) and a control group (134 patients each) based on whether or not they used G-CSF. All patients in the priming group but not the control group received subcutaneous G-CSF priming injection on superovulation initiation day. Then, each group underwent 1 cycle of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), because all groups adopted PPOS protocol, which required freezing of all transferable embryos, and thawing embryos for transfer.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBefore propensity score matching, there were statistically significant differences in number of 2PN(6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74 vs4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), number of eggs retrievals(8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16 vs 6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), number of total fertilization(7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.69 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0), number of transferable embryos(6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74 vs 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0) and number of cleavage(7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75 vs 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0) were significantly improved by priming. After the propensity score matching(1:1),There were statistically significant differences in number of MII (4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15 vs 6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77 \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0).The number of 2PN (5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.55 vs 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1), number of eggs retrievals(7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.17 vs 6.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.3), number of total fertilization(6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57 vs 5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1), number of transferable embryos(6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.58 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92,P\u0026thinsp;=\u0026thinsp;0.1) and number of cleavage(6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64 vs 5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1) tended to be higher in 33 G-CSF patients than in 33 controls, although statistical significance was not attained respectively. After matching propensity scores(1:2),there were statistically significant differences in number of transferable embryos(6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.62 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49,\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045), were significantly improved by priming. The number of 2PN (5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.60 vs 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.17), number of eggs retrievals (8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30 vs 6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.285), number of total fertilization (6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64 vs 5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.087), and number of cleavage (6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71 vs 5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.73, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08) tended to be higher in 31 G-CSF patients than in 52 controls, although statistical significance was not attained respectively. In addition, the G-CSF patients achieved more cryopreservation of transplantable embryos than the control group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe administration of G-CSF during Superovulation day of ART cycle can improve embryonic development potential of patients with poor ovarian reserve, with a view to improving future clinical pregnancy rates and live birth rates.\u003c/p\u003e","manuscriptTitle":"Granulocyte colony-stimulating factor priming improves egg and embryo quality in patients with poor ovarian reserve: a retrospective case study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-15 20:16:08","doi":"10.21203/rs.3.rs-3997062/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":"fe684dc3-094d-4237-a429-0ed0ca2b6d5f","owner":[],"postedDate":"March 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29434639,"name":"Biological sciences/Drug discovery"},{"id":29434640,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2024-07-05T06:10:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-15 20:16:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3997062","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3997062","identity":"rs-3997062","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}