Impact of Intrauterine Infusion vs. Subcutaneous G-CSF Injection on Endometrial Immunomodulation and Angiogenesis in Infertile Women Undergoing IUI-Scilight

Trends in Immunotherapy

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Impact of Intrauterine Infusion vs. Subcutaneous G-CSF Injection on Endometrial Immunomodulation and Angiogenesis in Infertile Women Undergoing IUI

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https://doi.org/10.54963/ti.v9i3.1324
Mahmood, Z. A. Q., Al‑Anbari, L. A., & Al‑Obaidi, M. T. (2025). Impact of Intrauterine Infusion vs. Subcutaneous G-CSF Injection on Endometrial Immunomodulation and Angiogenesis in Infertile Women Undergoing IUI. Trends in Immunotherapy, 9(3), 93–109. https://doi.org/10.54963/ti.v9i3.1324
Volume 9 Issue 3 (September 2025) (in progress)
Copyright (c) 2025 Zainab Abdul Qader Mahmood, Lubna Amer Al‑Anbari, Manal Taha Al‑Obaidi
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Authors

  • Zainab Abdul Qader Mahmood

    Department of Physiology, High Institute for Infertility Diagnosis and Assisted Reproductive Technologies (ART), Al‑Nahrain University Al‑Kadhimiya, Baghdad +964, Iraq
  • Lubna Amer Al‑Anbari

    Department of Physiology, High Institute for Infertility Diagnosis and Assisted Reproductive Technologies (ART), Al‑Nahrain University Al‑Kadhimiya, Baghdad +964, Iraq
  • Manal Taha Al‑Obaidi

    Department of Physiology, High Institute for Infertility Diagnosis and Assisted Reproductive Technologies (ART), Al‑Nahrain University Al‑Kadhimiya, Baghdad +964, Iraq

Received: 20 June 2025; Revised: 30 June 2025; Accepted: 14 July 2025; Published: 30 July 2025

Infertility remains a significant global health concern, with endometrial receptivity recognized as a critical factor influencing successful implantation. Granulocyte‑Colony Stimulating Factor (G‑CSF), a hematopoietic cytokine, has recently emerged as a potential therapeutic agent for enhancing endometrial function and modulating immune responses during assisted reproductive procedures. This study aims to investigate the effect of intrauterine infusion versus subcutaneous injection of G‑CSF on immunological and angiogenic markers related to endometrial receptivity in infertile women undergoing intrauterine insemination (IUI). A total of 75 infertile females were enlisted in this prospective interventional comparative trial and were equally divided into three groups: the intrauterine infusion group, the subcutaneous injection group, and the control group (no G‑CSF administration). Baseline demographic and hormonal characteristics, as well as ultrasound and immunological parameters, were recorded before and after G‑CSF administration. Statistical analysis showed no significant differences in demographic and baseline clinical, hormonal, and biochemical characteristics across the groups. Post‑intervention, both G‑CSF groups demonstrated significant improvements in endometrial vascularity indices (pulsatility index, resistance index, and V1/V2 ratio) compared to the control group, despite the endometrial thickness not differing significantly. Serum levels of TNF‑α significantly decreased, while VEGF levels increased significantly post‑G‑CSF in all groups; IL‑10 levels increased but reached significance only in the subcutaneous and control groups. These outcomes indicate that G‑CSF may enhance endometrial receptivity via improved vascular and immunological parameters, although the effect remains inconclusive and requires further validation.

Keywords:

Endometrial Immunomodulation Granulocyte Colony‑Stimulating Factor Intrauterine Insemination Interleukin‑10 Tumor Necrosis Factor‑Alpha Vascular Endothelial Growth Factor

References

  1. Ali, A.A.; Al-Hilli, N.; Jawad, M.A. Effect of Obesity on ICSI Outcome in Iraqi Infertile Females. Biochem. Cell. Arch. 2020, 20, 2.
  2. Al-Anbari, L.; Abunaila, R.S.H.; Mufeda, A.A.; et al. Oral Intake of Salvia officinalis Improves Intrauterine Insemination Outcomes in Women With Polycystic Ovary Syndrome. Ginekol. Poloznictwo 2025, 1, 001–005.
  3. Kadhim, B.; Salman, M.; Jwad, M. Comparison Between the Effect of Atosiban and Piroxicam Administration Before Embryo Transfer on In Vitro Fertilization Outcome. PhOL. 2021, 1, 511–516.
  4. Ali, H.F.; Abbood, M.S. Correlation Study Between Level of Zinc and Lead in Serum and Seminal Plasma in Infertile Patients. Ann. Trop. Med. Public Health 2020, 23, 16.
  5. Abdulhussain, A.F.; Ghazi, H.F.; Abood, M.S. Measurement of Seminal Plasma MYD88 Protein and Bacterial Lipopolysaccharide in Infertile Male as an Indicator for Leukocytospermia and Bad Seminal Fluid Analysis. Ann. Trop. Med. Public Health 2020, 23, 16.
  6. Thaker, A.Z.; Al-Anbari, L.A.; Al-Essawe, E.M. Dual Trigger Strategy After Controlled Stimulation Intrauterine Insemination Cycle Did Not Influence the Pregnancy Outcome Compared With Standard HCG Trigger Only Protocol. Wiad. Lek. 2022, 75, 1268–1273.
  7. Ali, Z.H.; Mossa, H.A.L.; Abood, M.S. Evaluation of Endometrial Receptivity and Pregnancy Outcome in View of Assessment of Serum and Follicular Fluid Level of CD44 Following Administration of Hyaluronic Acid to Infertile Women. Pharmacologyonline 2021, 3, 536–544.
  8. Shihab, E.M.; Ahmed, H.N.; Ahmed, I.T.; et al. The Story of Oral Contraceptive Users and Bacterial Vaginosis… Is It Real? Int. J. Pharm. Res. 2020, 12, 1809–1818.
  9. Tawfeeq, A.T.; Abbood, M.S.; Mufeda, A.-A. The Comparison Between the Effect of Different Medical Drugs Used to Improve Endometrial Receptivity in Patients With Thin Poorly Vascularized Endometrium. Iraqi J. Embryos Infertil. Res. 2023, 13, 99–115.
  10. Jawad, H.H.; Al-Anbari, L.; Abbood, M. Assessment of the Relationship of Basal Serum Anti Mullerian Hormone Levels and Maternal Age With Pregnancy Outcome in Patients Undergoing ICSI. Ann. Trop. Med. Public Health 2020, 23, 4.
  11. Abunaila, R.s.H.; Al-Anbari, L.A.; Abbood, M.S. The Effects of Adding Gonadotropin-Releasing Hormone Antagonist on Cycle Characteristics and Pregnancy Rate in Stimulated Intrauterine Insemination (IUI) Cycle. Int. J. Res. Pharm. Sci. 2020, 11, 3053–3060.
  12. Abbood, M.S.; Hassan, M.F.; Nashtar, S.B. Effectiveness and Safety of Highly Purified Human Menopausal Gonadotropin in Hyper Responder Iraqi Females Undergoing Intracytoplasmic Sperm Injection. Al-Kindy Coll. Med. J. 2025, 21, 53–57.
  13. Mohammed, Z.A.; Jawad, H.H.; Al-Anbari, L.; et al. Comparison Between the Effect of GnRH Agonist and HCG Injection on the Luteal Phase Support in Patient Undergoing IUI. J. Int. Dent. Med. Res. 2020, 13, 1504–1509.
  14. Aubead, N.M.; Al Ghazali, B.S.; Abbood, M.S. A Comparison Between Luteal Phase Treatment With Estradiol and GnRH Antagonist for Ovarian Follicular Synchronization in ICSI Cycle. Indian J. Public Health Res. Dev. 2019, 10, 1229–1235.
  15. Jaafar, F.R.; Attarbashee, R.K.; Abu-Raghif, A.R.; et al. Gemifloxacin Ameliorates Acetic Acid-Induced Ulcerative Colitis via Modulation of Inflammatory, Oxidative, and Adhesive Biomarkers and Histopathological Changes in Rats. J. Mol. Histol. 2025, 56, 250.
  16. Rasool, G.S.; Al-Anbari, L.; Habbas, A.H.; et al. Enhanced Endometrial Receptivity via Epigallocatechin Gallate (EGCG)-Loaded Menstrual Blood-Derived Exosomes. J. Pharm. Sci. 2025, 114, 7.
  17. Dawood, S.A.; Hussaini, H.A.; Ali, M. Effect of Oral Estradiol Valerate Versus Vaginal Sildenafil on Endometrial Receptivity Evaluated by Ultrasound and Pregnancy Rate in Iraqi Infertile Females. Syst. Rev. Pharm. 2020, 11, 627–632.
  18. Alhussien, Z.A.; Mossa, H.A.L.; Abood, M.S. The Effect of L-Carnitine on Apoptotic Markers (Annexin V and Clusterin) in Polycystic Ovarian Syndrome Women Undergoing ICSI. Int. J. Drug Deliv. Technol. 2022, 12, 1682–1686.
  19. Adamczak, R.; Al-Anbari, L.; Mossa, H.A.L.; et al. Function of Follicular Cytokines: Roles Played During Maturation, Development and Implantation of Embryo. Medicina 2021, 57, 1251.
  20. Hussein, Z.A.; Abu-Raghif, A.R.; Tahseen, N.J.; et al. Vinpocetine Alleviated Alveolar Epithelial Cells Injury in Experimental Pulmonary Fibrosis by Targeting PPAR-γ/NLRP3/NF-κB and TGF-β1/Smad2/3 Pathways. Sci. Rep. 2024, 14, 11131.
  21. Hussein, Z.A.; Abu-Raghif, A.R.; Fawzi, H.A. The Mitigating Effect of Para-Hydroxycinnamic Acid in Bleomycin-Induced Pulmonary Fibrosis in Mice Through Targeting Oxidative, Inflammatory and Fibrotic Pathways. Basic Clin. Pharmacol. Toxicol. 2024, 135, 23–42.
  22. Naji, M.E.; Mossa, H.A.L.; Ali, Z.H.; et al. Effect of Convolvulus arvensis Ethanolic Extract on Testosterone-Induced Alopecia in Mice. Int. J. Drug Deliv. Technol. 2022, 12, 1070–1075.
  23. Abbas, A.H.; Abbood, M.S.; Ridha-Salman, H.; et al. Suppressive Effect of Topical Moxifloxacin on Imiquimod-Induced Model of Psoriasis in Mice. Naunyn-Schmiedeberg's Arch. Pharmacol. 2025, 1–20.
  24. Habbas, A.H.; Abu-Raghif, A.R.; Ridha-Salman, H.; et al. Therapeutic Effect of Bosentan on 2,4-Dinitrochlorobenzene (DNCB)-Induced Atopic Dermatitis Mouse Model. Arch. Dermatol. Res. 2025, 317, 436.
  25. Jaafar, F.R.; Abu-Raghif, A. Comparative Treatment of Sulfasalazine + Ezetimibe Combination and Sulfasalazine in a Rat Model With Induced Colitis. J. Med. Life 2023, 16, 1165.
  26. Luty, R.S.; Al-Zubaidy, A.A.; Malik, A.S.; et al. Protective Effect of Orientin on Diabetic Nephropathy in Rat Models of High-Fat Diet and Streptozotocin-Induced Diabetes. Naunyn-Schmiedeberg's Arch. Pharmacol. 2025, 1–16.
  27. Raheem, A.K.K.; Abu-Raghif, A.R.; Zigam, Q.A. Cilostazol Protects Against Sepsis-Induced Kidney Impairment in a Mice Model. J. Med. Chem. Sci. 2023, 6, 1193–1203.
  28. Attarbashee, R.K.; Hamodat, H.F.; Mammdoh, J.K.; et al. The Possible Effect of Bosentan on the Methotrexate-Induced Salivary Gland Changes in Male Rats: Histological and Immunohistochemical Study. Toxicol. Res. 2025, 14, 1.
  29. Luty, R.S.; Abbas, S.F.; Haji, S.A.; et al. Hepatoprotective Effect of Catechin on Rat Model of Acetaminophen-Induced Liver Injury. Comp. Clin. Pathol. 2025, 1–14.
  30. Ali, B.F.; Abu-Raghif, A.R.; Ridha-Salman, H.; et al. Vildagliptin Topical Ointment: An Effective Treatment for Imiquimod-Induced Psoriasis in Mice. J. Mol. Histol. 2025, 56, 143.
  31. Aal-Aaboda, M.; Abu Raghif, A.; Hadi, N. Renoprotective Potential of the Ultra-Pure Lipopolysaccharide from Rhodobacter Sphaeroides on Acutely Injured Kidneys in an Animal Model. Arch. Razi Inst. 2021, 76, 1755–1764.
  32. Raheem, A.K.; Abu-Raghif, A.R.; Abbas, A.H.; et al. Quercetin Mitigates Sepsis-Induced Renal Injury via Inhibiting Inflammatory and Oxidative Pathways in Mice. J. Mol. Histol. 2025, 56, 184.
  33. Khalaf, O.I.; Hussaini, H.A.; Al-Obaidi, M.T. Effects of Intrauterine Human Chorionic Gonadotropin on Endometrial Receptivity in Intracytoplasmic Sperm Injection Cycle. Al-Anbar Med. J. 2025, 21, 1.
  34. Guzeloglu-Kayisli, O.; Kayisli, U.A.; Taylor, H.S. The Role of Growth Factors and Cytokines During Implantation: Endocrine and Paracrine Interactions. Semin. Reprod. Med. 2009, 27, 62–79.
  35. Thammer, M.R.; Sahib, H.B.; Ridha-Salman, H. Skin Healing Potential of Bioactive Components from Lycoperdon lividum Mushroom Versus β-Sitosterol in Rat Model of Burn Wounds. Microsc. Res. Tech. 2025, 88, 1–53.
  36. Khorsheed, S.M.; Abu-Raghif, A.; Ridha-Salman, H. Alleviative Effects of Combined Topical Melatonin and Rutin on Imiquimod-Induced Psoriasis Mouse Model. Pharmacia 2024, 71, 1–13.
  37. Khaleel, B.J.; Ridha-Salman, H.; Kadhim, H.M.; et al. Inhibitory Effects of Carbohydrazide Indole Derivative on Micro-Blood Vessel Growth Using Ex Vivo, In Vivo, and In Vitro Assays. In Vitro Cell. Dev. Biol. Anim. 2025, 1–15.
  38. Ferrara, N.; Gerber, H.P.; LeCouter, J. The Biology of VEGF and Its Receptors. Nat. Med. 2003, 9, 669–676.
  39. Khaleel, B.J.; Ridha-Salman, H.; Kadhim, H.M.; et al. Anti-Angiogenic and Anti-Oxidant Effects of 2-NTI Indole Derivative vs. Suramin in Ex Vivo, In Vivo, and In Vitro Studies. Cytotechnology 2025, 77, 38.
  40. Abu-Raghif, A.R.; Sahib, H.B.; Hanoon, M.M. Anti-Angiogenic Activity of Zizyphus Spina-Christi Leaves Extracts. Int. J. Pharm. Sci. Rev. Res. 2015, 35, 32.
  41. Abaid, W.A.; Al-Obaidi, M.T.; Abood, M.S. Intrauterine Infusion of Autologous Platelet-Rich Plasma Affects the Endometrial Thickness, Epidermal Growth Factor and Pregnancy Outcome in Patients Undergoing IUI. Iraqi J. Embryos Infertil. Res. 2020, 9, 18–38.
  42. Guo, X.; Zhao, Y.; Chen, T.; et al. Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications. Biomolecules 2021, 11, 253.
  43. Hannan, N.; Paiva, P.; Dimitriadis, E.; et al. Analysis of Fertility-Related Soluble Mediators in Human Uterine Fluid Identifies VEGF as a Key Regulator of Embryo Implantation. Endocrinology 2011, 152, 4948–4956.
  44. Abdulhameed, O.A.; Kadhim, H.M. Exploring the Role of Pleurotus Ostreatus as an Ointment Formulation in Inducing Wound Healing in Mice Skin. J. Pharm. Bioall. Sci. 2024, 16, S243–S246.
  45. Alteef, L.W.A.; Al-Awadi, S.J.; Al-Obaidi, M.T. Genetic Polymorphism and Serum Level of Vascular Endothelial Growth Factor Associated with First Trimester Pregnancy Outcome in ICSI Program. World. J. Pharm. Res. 2017, 6, 67–76.
  46. Benkhalifa, M.; Guillemin, C.; Soumeya, T.; et al. Circulating MMP-7 and VEGF as Potential Predictive Biomarkers for Recurrent Implantation Failures. Zygote 2021, 29, 365–371.
  47. ALfil, A.; Al-Anbari, L.A. Single Dose of Granulocyte-Colony Stimulating Factor Use to Improve Intracytoplasmic Sperm Injection Outcomes. Iraqi J. Embryos Infertil. Res. 2023, 13, 60–72.
  48. Al-Jubouri, W.M.; Al-Obaidi, M.T.; Hussaini, H.A. Endometrial Perfusion with Granulocyte Colony-Stimulating Factor in Infertile Women. Pharmacol. Online 2021, 417–425.
  49. He, Y.; Li, Y.; Zhang, Y.; et al. Subcutaneous Injection Granulocyte Colony-Stimulating Factor (G-CSF) Is Superior to Intrauterine Infusion on Patients with Recurrent Implantation Failure: A Systematic Review and Network Meta-Analysis. J. Reprod. Immunol. 2024, 163, 104250.
  50. Witte, M.; Thomas, M.; Fuchs, P.; et al. Regulation of Angiogenesis. In Regul. Angiogen; Goldberg, I.D., Rosen, E.M., Eds.; Birkhäuser: Basel, Switzerland, 2013; 79, pp. 65–112.
  51. Zurochka, A.; Karpenko, I.; Lezhnev, S.; et al. Immunobiological Properties of Granulocyte-Macrophage Colony-Stimulating Factor and Synthetic Peptides of His Active Center. Med. Immunol. (Russ.) 2021, 23, 1031–1054.
  52. Lu, J.K.; Tang, Y.; Wang, X.; et al. Variability and Implications of Recurrent Implantation Failure Definitions Used in the Scientific Literature: A Systematic Review. Hum. Reprod. Open 2025, hoaf033.
  53. Zhou, L.; Zhou, L. The Mechanisms and Therapeutic Effects of Granulocyte Colony-Stimulating Factor in Reproduction. Reprod. Biol. Endocrinol. 2025, 23, 1–10.
  54. Khalil, R.; Mossa, H.; Jwad, M. Mitofusin 1 as a Marker for Embryo Quality and Development in Relevance to ICSI Outcome in Infertile Females. Georgian Med. News 2023, 345, 58–61.
  55. Narayana, N.; Dasari, M.; Reddy, M.M.; et al. Intrauterine G-CSF in IUI Cycles for Women with Thin Endometrium May Improve Endometrial Thickness and Pregnancy Rates: A Randomized Controlled Study. Med. J. Armed Forces India 2025, 81, 410–415.
  56. Eftekhar, M.; Sayadi, M.; Arabjahvani, F. Transvaginal Perfusion of G-CSF for Infertile Women with Thin Endometrium in Frozen ET Program: A Non-Randomized Clinical Trial. Iran J. Reprod. Med. 2014, 12, 661–666.
  57. Kalem, Z.; Kalem, M.N.; Bakirarar, B.; et al. Intrauterine G-CSF Administration in Recurrent Implantation Failure (RIF): An RCT. Sci. Rep. 2020, 10, 5139.
  58. Aleyasin, A.; Agha-Hosseini, M.; Safdarian, L.; et al. Granulocyte Colony-Stimulating Factor in Repeated IVF Failure: A Randomized Trial. Reproduction 2016, 151, 637–642.
  59. Rahmatullah, W.S.; Zahroh, H.; Lestari, F. Role of Vascular Endothelial Growth Factor (VEGF) and Doppler Sub-Endometrial Parameters as Predictors of Successful Implantation in Intracytoplasmic Sperm Injection (ICSI) Patients. Siriraj Med. J. 2020, 72, 1.
  60. Abbod, M.S.; Hanoon, M.M.; Sahib, H.B.; et al. Antiatherosclerotic Effect of L-Thyroxine and Verapamil Combination on Thoracic Aorta of Hyperlipidemic Rabbits. Int. J. Pharm. Sci. Rev. Res. 2014, 27, 254–260.
  61. Al-Hamadani, I.T.; Shehab, E.M.; Aziz, N.A. Comparative Changes in Sexual Dysfunction of Married Women After Colpoperineorrhaphy Versus Colpoperineorrhaphy with Additional Platelet Rich Plasma Injection. Indian J. Forensic Med. Toxicol. 2019, 13, 314–320.
  62. Madbouly, K.; Heidar, N.F.A.; Elsaid, S.A.; et al. Postwash Total Motile Sperm Count: Should It Be Included as a Standard Male Infertility Work-Up. Can. J. Urol. 2017, 24, 8847–8852.
  63. Aydin, S. A Short History, Principles, and Types of ELISA, and Our Laboratory Experience with Peptide/Protein Analyses Using ELISA. Peptides 2015, 72, 4–15.
  64. Abdulbari, A.S.; Ali, N.M.; Abu-Raghif, A.R.; et al. Impact of Azithromycin on Specific Biochemical Markers and Sebum Composition in Acne Vulgaris Patients. Arch. Dermatol. Res. 2025, 317, 798.
  65. Ali, K.A.; Abu-Raghif, A.R.; Ridha-Salman, H. Evaluation of Common Topical Therapeutic Agents of Plane Warts. Arch. Dermatol. Res. 2025, 317, 246.
  66. Abbas, A.H.; Abbas, Z.H.; Ridha-Salman, H.; et al. The Attenuated Effects of Topical Empagliflozin on Imiquimod-Induced Model of Psoriasis in Mice. J. Trop. Life Sci. 2024, 14, 459–468.
  67. Hassan, Z.Y.; Hassan, T.Y.; Abu-Raghif, A.R. Evaluation the Effect of Phytosterol Fraction of Chenopodium Murale in Comparison with Tacrolimus on Mice Induced Atopic Dermatitis. Iraqi J. Pharm. Sci. 2023, 32, 84–91.
  68. AL-Bairmani, R.J.; Kadhim, H.M. Evaluation of Anti-Aging Effects of Gemfibrozil on D-Galactose Induced Aging Mouse Model. Int. J. Drug Deliv. Technol. 2023, 13, 1011–1016.
  69. Mannava, L.L. A Comparative Study on Ovulation Induction with Clomiphene Citrate Versus Letrozole in Women with Infertility: A Prospective Randomized Trial at Infertility Clinic, KVG Medical College and Hospital Sullia.Master Thesis, Rajiv Gandhi University of Health Sciences, India, 15 November 2019.
  70. Balasch, J. Gonadotrophin Ovarian Stimulation and Intrauterine Insemination for Unexplained Infertility. Reprod. Biomed. Online 2004, 9, 664–672.
  71. Indrayan, A.; Malhotra, R.K. Medical Biostatistics, 4th ed.; Chapman & Hall/CRC: New York, NY, USA, 2017; pp. 1–1032.
  72. Mehta, H.M.; Malandra, M.; Corey, S.J. G-CSF and GM-CSF in Neutropenia. J. Immunol. 2015, 195(4), 1341–1349.
  73. Piccinni, M.P.; Beloni, G.; Giudizi, M.G.; et al. Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction. Front. Immunol. 2021, 12, 717808.
  74. Khorsheed, S.M.; Raghif, A.R.A. Anti-Proliferative, Anti-Oxidant and Anti-Inflammatory Effects of Topical Rutin on Imiquimod-Induced Psoriasis in Mice. Pak. J. Life Soc. Sci. 2024, 22, 1962–1976.
  75. Ali, B.F.; Abu-Raghif, A.R.; Ridha-Salman, H. Protective Effect of Cinnarizine on Imiquimod-Induced Mouse Model of Psoriasis. J. Res. Pharm. 2025, 29, 1783–1791.
  76. Yahiya, Y.I.; Naji, M.N.; Nori, R.N.; et al. Protective Effect of IAXO-102 on Renal Ischemia-Reperfusion Injury in Rats. J. Med. Life 2023, 16, 623–630.
  77. Dawood, J.O.; Abu-Raghif, A. Labetalol Ameliorates Experimental Colitis in Rat Possibly Through Its Effect on Proinflammatory Mediators and Oxidative Stress. Clin. Lab. 2024, 70, 353–362.
  78. Dawood, J.O.; Abu-Raghif, A. Moxifloxacin Ameliorates Clinical Disease Activity and Histopathological Changes of Acetic Acid-Induced Colitis Model in Rat Possibly Through Its Effect on Proinflammatory Mediators and Oxidative Stress. Adv. Life Sci. 2023, 10, 106–112.
  79. Abdul-Majeed, Z.M.; Al-Atrakji, M.Q.Y.M.A.; Ridha-Salman, H. Cranberry Extract Attenuates Indomethacin-Induced Gastric Ulcer in Rats via Its Potential Antioxidant and Anti-Inflammatory Effects. J. Mol. Histol. 2025, 56, 206.
  80. Khafaji, A.W.M.; Al-Zubaidy, A.A.K.; Farhood, I.G.; et al. Ameliorative Effects of Topical Ramelteon on Imiquimod-Induced Psoriasiform Inflammation in Mice. Naunyn Schmiedebergs Arch. Pharmacol. 2024, 397, 6231–6248.
  81. Liu, M.; Sun, Y.; Wang, D.; et al. Peri-Implantation Treatment with TNF-α Inhibitor for Endometriosis and/or Adenomyosis Women Undergoing Frozen-Thawed Embryo Transfer: A Retrospective Cohort Study. J. Reprod. Immunol. 2025, 167, 104415.
  82. Ridha-Salman, H.; Shihab, E.M.; Hasan, H.K.; et al. Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis. ACS Pharmacol. Transl. Sci. 2024, 7, 1–16.
  83. Ridha-Salman, H.; Al-Zubaidy, A.A.; Abbas, A.H.; et al. The Alleviative Effects of Canagliflozin on Imiquimod-Induced Mouse Model of Psoriasis-Like Inflammation. Naunyn Schmiedebergs Arch. Pharmacol. 2024, 398, 1–21.
  84. Robertson, S.A.; Chin, P.Y.; Femia, J.G.; et al. Immune Determinants of Endometrial Receptivity: A Biological Perspective. Fertil. Steril. 2022, 117, 1107–1120.
  85. Jawad, M.A.; Al-Jubouri, A.A.; Alwan, N.T.; et al. Effect of Alcohol Extract of Prunus Avium on In Vitro Sperm Activation of Human Semen Samples. Int. J. Pharm. Sci. Rev. Res. 2014, 25, 65–68.
  86. Abdullah, M.A.; Abdulhamed, W.A.; Abood, M.S. Effects of Vaginal Sildenafil Citrate on Ovarian Blood Flow and Endometrial Thickness in Infertile Women Undergoing Intra-Uterine Insemination. Int. J. Drug Deliv. Technol. 2021, 11, 1450–1453.
  87. Dawood, S.A.; Mossa, H.A.L.; Jwad, M.A. Influence of Obesity and Insulin Resistance on the Reproductive Outcome of Iraqi Women Undergoing Intracytoplasmic Sperm Injection. Al-Rafidain J. Med. Sci. 2024, 6, 179–187.
  88. González-Rodríguez, A.; Labad, J.; Navarro, C.; et al. Women Undergoing Hormonal Treatments for Infertility: A Systematic Review on Psychopathology and Newly Diagnosed Mood and Psychotic Disorders. Front. Psychiatry 2020, 11, 479.
  89. Guzeloglu-Kayisli, O.; Kayisli, U.A.; Taylor, H.S. The Role of Growth Factors and Cytokines During Implantation: Endocrine and Paracrine Interactions. Semin. Reprod. Med. 2009.
  90. Salman, H.R.; Alzubaidy, A.A.; Abbas, A.H.; et al. Attenuated Effects of Topical Vinpocetine in an Imiquimod-Induced Mouse Model of Psoriasis. J. Taibah Univ. Med. Sci. 2024, 19, 35–53.
  91. Herez, S.H.; Jawad, M.A.; Abbood, M.S. Effect of Bisphenol A Level in Follicular Fluid on ICSI Outcome. J. Pharm. Negat. Results 2022, 13, 370–376.
  92. Al-Yasiry, R.Z.; Jawad, M.A.; Abbood, M.S. Association of Methylenetetrahydrofolate Reductase Gene Polymorphism C677T with Oocyte Number and Embryo Quality in Iraqi Infertile Women Undergoing Intracytoplasmic Sperm Injection. Al-Rafidain J. Med. Sci. 2024, 6, 39–45.
  93. Alfil, A.; Al Anbari, L. Repeated Subcutaneous Granulocyte Colony Stimulating Factor Effect in Clinical Pregnancy Rate. Adv. Life Sci. 2024, 10, 639–643.
  94. Abu-Raghif, A.R.; Alkazzaz, A.M.; Fadheel, Q.J. A Comparative Study of the Effect of Thyme and Calcium with Vitamin D3 in Treatment of Postmenopausal Women with Osteoporosis. Res. J. Pharm. Biol. Chem. Sci. 2016, 9, 260–268.
  95. Jain, S.; Mahey, R.; Malhotra, N.; et al. Effect of Intrauterine Perfusion of Granulocyte Colony-Stimulating Factor on Endometrial Parameters and In Vitro Fertilization Outcome in Women Undergoing In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Randomized Controlled Trial. J. Hum. Reprod. Sci. 2018, 11, 254–260.
  96. Alfil, A.; Al-Anbari, L.A. Single Dose of Granulocyte-Colony Stimulating Factor Use to Improve Outcomes in Patient Undergoing Intracytoplasmic Sperm Injection. Iraqi J. Embryos Infertil. Res. 2023, 13.
  97. Jiang, Y.; Zhao, Q.; Zhang, Y.; et al. Treatment of G-CSF in Unexplained, Repeated Implantation Failure: A Systematic Review and Meta-Analysis. J. Gynecol. Obstet. Hum. Reprod. 2020, 49, 101866.
  98. Zhang, B.; Xu, J.; Wei, X.; et al. The Role of Granulocyte Colony Stimulating Factor in Mitigating the Risk of Recurrent Miscarriages: A Comprehensive Review and Meta-Analysis. Reprod. Sci. 2024, 1, 1–9.
  99. Fu, L.L.; Xu, Y.; Yan, J.; et al. Efficacy of Granulocyte Colony-Stimulating Factor for Infertility Undergoing IVF: A Systematic Review and Meta-Analysis. Reprod. Biol. Endocrinol. 2023, 21, 34.
  100. Zhang, C.H.; Chen, C.; Wang, J.R.; et al. An Endometrial Receptivity Scoring System Basing on the Endometrial Thickness, Volume, Echo, Peristalsis, and Blood Flow Evaluated by Ultrasonography. Front. Endocrinol. 2022, 13, 907874.
  101. Gleicher, N.; Kim, A.; Michaeli, T.; 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, 172–177.
  102. Narayana, N.; Khurana, A.; Rai, S.; et al. Intrauterine G-CSF in IUI Cycles for Women with Thin Endometrium May Improve Endometrial Thickness and Pregnancy Rates: A Randomized Controlled Study. Med. J. Armed Forces India 2024.
  103. Zhao, J.; Xu, B.; Xie, S.; et al. Whether G-CSF Administration Has Beneficial Effect on the Outcome After Assisted Reproductive Technology? A Systematic Review and Meta-Analysis. Reprod. Biol. Endocrinol. 2016, 14, 1–9.
  104. Sweed, A.; Hamid, A.A.S.A.; Mahmoud, M.S.; et al. Efficacy of Granulocyte Colony Stimulating Factor (G-CSF) for Improving Endometrial Thickness in IVF/ICSI Patients with Thin Endometrium: A Meta-Analysis and Systematic Review. Evid. Based Women’s Health J. 2025, 15, 1–8.
  105. Ferrara, N.; Kerbel, R.S. Angiogenesis as a Therapeutic Target. Nature 2005, 438, 967–974.
  106. Umapathy, A.; Chamley, L.W.; James, J.L. Reconciling the Distinct Roles of Angiogenic/Anti-Angiogenic Factors in the Placenta and Maternal Circulation of Normal and Pathological Pregnancies. Angiogenesis 2020, 23, 105–117.
  107. Mohamed, T. An Evaluation of the Use of G-CSF as an Adjunct to IVF in Women Who Have Previously Failed Attempts at Pregnancy with IVF. Master’s Thesis, University of the Witwatersrand, Johannesburg, South Africa, 14 July 2017.
  108. Al-Tamemi, K.I.A.; Abood, M.S.; Al-Ammar, M.A. Effect of Intrauterine Flushing of HCG on Day of Trigger on IUI Outcome. Pharmacologyonline 2021, 2, 890–903.
  109. Yang, Y.; Ru, H.; Zhang, S.; et al. The Effect of Granulocyte Colony-Stimulating Factor on Endometrial Receptivity of Implantation Failure Mouse. Reprod. Sci. 2024, 1, 1–18.
  110. Dickerson, A.G.; Joseph, C.A.; Kashfi, K. Current Approaches and Innovations in Managing Preeclampsia: Highlighting Maternal Health Disparities. J. Clin. Med. 2025, 14, 1190.
  111. Su, Q.; Pan, Z.; Yin, R.; et al. The Value of G-CSF in Women Experienced at Least One Implantation Failure: A Systematic Review and Meta-Analysis. Front. Endocrinol. 2024, 15, 1370114.
  112. Kou, L.; Jiang, X.; Xiao, S.; et al. Therapeutic Options and Drug Delivery Strategies for the Prevention of Intrauterine Adhesions. J. Control. Release 2020, 318, 25–37.
  113. Tigue, C.; McKoy, J.M.; Evens, A.M.; et al. Granulocyte-Colony Stimulating Factor Administration to Healthy Individuals and Persons with Chronic Neutropenia or Cancer: An Overview of Safety Considerations from the Research on Adverse Drug Events and Reports Project. Bone Marrow Transplant. 2007, 40, 185–192.
  114. Alves, A.R.; Dias, M.F.; Silvestre, M. Endometrial Fluid Biomarkers and Their Potential as Predictors of Successful Embryo Implantation. BioMedicine 2023, 13, 1.
  115. Ruiz-Alonso, M.; Blesa, D.; Díaz-Gimeno, P.; et al. The Endometrial Receptivity Array for Diagnosis and Personalized Embryo Transfer as a Treatment for Patients with Repeated Implantation Failure. Fertil. Steril. 2013, 100, 818–824.
  116. Dakre, S.M.; More, A.; Dutta, S.; et al. Combination Therapy with Platelet-Rich Plasma (PRP) and Granulocyte Colony-Stimulating Factor (G-CSF) for Thin Endometrium: A Case Report. Cureus 2024, 16, e54378.