Granulocyte Colony Stimulating Factor-GCSF For Endometrial growth-Dr Pavithra.E

CAUSES OF THIN ENDOMETRIUM

  • Endometrial resistance to circulating estrogen
  • Reduced blood flow to the endometrium
  • Over exposure to testosterone
  • Permanent damage to the basal endometrium
  • Infection like MTB
  • Asherman syndrome

PERSISTANT THIN ENDOMETRIUM

  • Evaluate for STB-incidence of genital tuberculosis is very high in India.
  • For all practical purposes, completely damaged basal endometrium cannot be regenerated
  • Permanent damage to basal endometrium may occur due to severe endometritis or due to vigorous curettage following abortion.

ENDOMETRIAL EVAULATION

  • Assessment by USG(TVS)
  • Hysteroscopy
  • Histology
  • MRI

TVS

  • Rapid noninvasive means of assessing the endometrium
  • Thickest part of the endometrium should be measured
  • Endometrium of 6mm or less is associated with 100% negative predicitive value for conception
  • ET 8-14mm is best endometrium on day of HCG trigger
  • ET >16mm or <7mm is not associated with good prognosis.

MODALITIES TO INCREASE ENDOMETRIUM

  • Oral estradiol 2mg TDS
  • High dose of Vitamin E
  • Oral L-arginine supplementation
  • Sildenafil Citrate 25mg TDS
  • Pentoxifylline
  • Low dose Aspirin
  • Nitroglycerine patch
  • G CSF

G-CSF

  • Gylcoprotein, growth factor and cytokine
  • Sources- endothelial cells, monocytes, macrophages and fibroblasts
  • Reproductive tract- follicular, granulosa cells, endometrial cells, and cells from decidual, placental and various fetal tissues
  • Promotes neutrophil proliferation and maturation
  • Produced by recombinant DNA technology from Ecoli into which the human G-CSF gene has been inserted.
  • G-CSF involved in a wide variety of reproductive functions:
    • Maintaining healthy endometrium
    • Useful biomarker of oocyte competence before fertilization

Improve implantation rate and successful pregnancy outcome in infertility, IUI and IVF procedures

PHARMOCOKINETICS

  • Absorption: not absorbed orally. Rapidly absorbed following C injection/infusion  into uterine cavity and peak serum concentrations are generally attained within 4-5 hours.
  • Distribution: Rapidly distubuted, highest concentration in bone marrow, adrenal glands, kidney and liver.
  • Half-life: is approx 3.5 hours, both SC or IV infusion.

Effect Of G-CSF on Endometrium

  • In endometrium G-CSF is secreted apically in polarized epithelial cells
  • G-CSF has been proposed as a treatment for implantation failure and repeated miscarriages.
  • A growth support in endometrial thickness can be observed within 48 hours of G-CSF administration.

Protocols Used:

1.Ovulation indication , trigger  with hcg 10,000 IU :>=1 Follicle >=19mm

2.Diagnosis of unresponsive thin endometrium :<7mm by ultrasound on the day of Hcg  administration.

3.G-CSF Endometrial Infusion: 300mcg/1ml (Filgastrim) approximately 6-12 hrs before Hcg administration and Repeated G-CSF infusion if endometrium <7mm on day of ovum pickup

Usage in IUI:

  1. Ovulation induction with CC or Gonadotropins
  2. Hcg 10,000 IU >=1 Follicle >=20mm
  3. Diagnosis of unresponsive thin endometrium <7mm by ultrasound on the day of hcg administration.
  4. G-CSF endometrial infusion:300mcg/1ml approximately6-12hrs before hcg administration
  5. Endometrium has been documented to grow between 1-4mm after the infusion

GCSF:

  1. Can be given both intrauterine and subcutaneously and also Intravenously[if being used iv to be diluted only in 5% dextrose and never in saline]
  2. Is given with 1ml insulin syringe 6-12 hrs before Hcg administration.
  3. Comes as 300mcg/ml

`Growth spurt in endometrial thickness can be observed within 48 hrs of GCSFadministration.

Evaluation of GCSF in thin endometrium:

Other Indications:

  1. For the treatment of thin endometrium
  2. Treatment option in patients with recurrent miscarriage.
  3. In Repeated embryo implantation failures in IVF.

Conclusion:

  1. G-CSF plays an important role in reproductive functions like ovulation and embryo implantation
  2. Infertile women with persistently thin endometrium may benefit from G-CSF
  3. Effective in Treatment of Unexplained RM and RIF.

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