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Filgrastim is a Granulocyte-Colony Stimulating factor (G-CSF). It is an FDA approved drug. Very small embryonic-like stem cells (VSELs) are found in the ovary. Animal studies showed that these cells are able to regenerate the affected ovary. Studies on mice have shown that Filgrastim result in recovery of oogenesis after chemotherapy-induced gonadal failure (in 2013, 2014, and 2015).
Premature ovarian insufficiency (POI) has no curative treatment until now. Filgrastim is an FDA approved Granulocyte-Colony Stimulating factor (G-CSF). Very small embryonic-like stem cells (VSELs) are found in the testis and ovary. VSELs are stem cells that have noticed to survive chemotherapy induced gonadal failure. Data from animal studies showed that stimulation of these stem cells result in generation of the affected gonads. Studies on mice have shown a promising stimulating effect of Filgrastim on recovery of spermatogenesis and oogenesis after chemotherapy-induced gonadal failure (in 2013, 2014, and 2015).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Filgrastim arm | Active Comparator | Intervention: Filgrastim vial (30 million IU/ml) SC injection twice daily for five consecutive days |
|
| Placebo arm | Placebo Comparator | Intervention: Injection of saline SC injection twice daily for five consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Filgrastim | Biological | Each case will have two intervention phases done blindly at random with a wash-out period of 6 months: Phase A: Filgrastim vial (30 million IU/ml) SC injection twice daily for five consecutive days. Phase B: Injection of saline SC injection twice daily for five consecutive days. |
| Measure | Description | Time Frame |
|---|---|---|
| Return of menses | Return of menses in patients with amenorrhea of at least 4 months | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pregnancy | Occurrence of pregnancy as diagnosed by positive serum B-hCG and/or ultrasound | 6 months |
| serum Estradiol | Normalization of serum Estradiol as tested bi-weekly |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mohammad AM Ahmed, MD | Egypt, Qena, South Valley University, faculty of Medicine | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23453120 | Background | Skaznik-Wikiel ME, McGuire MM, Sukhwani M, Donohue J, Chu T, Krivak TC, Rajkovic A, Orwig KE. Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy. Fertil Steril. 2013 Jun;99(7):2045-54.e3. doi: 10.1016/j.fertnstert.2013.01.135. Epub 2013 Feb 26. | |
| 25142624 |
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| ID | Term |
|---|---|
| D016649 | Primary Ovarian Insufficiency |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
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|
|
| Saline | Drug | Injection of saline SC injection twice daily for five consecutive days |
|
|
| 6 months |
| serum Anti-mullarian Hormone (AMH) | Normalization of serum AMH in patients with AMH level less than 0.9 ng/mL | 6 months |
| serum FSH | Normalization of serum FSH in patients with FSH level above 25 IU/L | 6 months |
| Follicular growth | Growth of follicle to size at least 18 mm as monitored by transvaginal ultrasound | 6 months |
| endometrial thickness | increase of endometrial thickness in women with thin endometrium (less then 8 mm) | 6 months |
| Akdemir A, Zeybek B, Akman L, Ergenoglu AM, Yeniel AO, Erbas O, Yavasoglu A, Terek MC, Taskiran D. Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model. J Gynecol Oncol. 2014 Oct;25(4):328-33. doi: 10.3802/jgo.2014.25.4.328. Epub 2014 Jun 18. |
| 25439845 | Background | Benavides-Garcia R, Joachim R, Pina NA, Mutoji KN, Reilly MA, Hermann BP. Granulocyte colony-stimulating factor prevents loss of spermatogenesis after sterilizing busulfan chemotherapy. Fertil Steril. 2015 Jan;103(1):270-80.e8. doi: 10.1016/j.fertnstert.2014.09.023. Epub 2014 Nov 5. |
| 26576728 | Background | Bhartiya D, Anand S, Parte S. VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation. J Ovarian Res. 2015 Nov 17;8:75. doi: 10.1186/s13048-015-0199-2. |
| 24833728 | Background | Roness H, Kalich-Philosoph L, Meirow D. Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents. Hum Reprod Update. 2014 Sep-Oct;20(5):759-74. doi: 10.1093/humupd/dmu019. Epub 2014 May 15. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D016298 |
| Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |