The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency

Study Overview
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Brief Summary
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The goal of this pilot study is to improve ovarian reserve markers in patients with premature ovarian insufficiency. The main question it aims to answer is: - Will treatment with G-CSF allow improvement in markers of ovarian reserve?

Detailed Description
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We hypothesize that treatment of premature ovarian insufficiency patients with G-CSF to mobilize bone marrow hematopoietic stem cells will allow for improved ovarian reserve markers including antral follicle count, anti-Mullerian hormone (AMH) levels and gonadotropin (FSH) levels. We anticipate these outcomes: Primary outcome: Decreased serum FSH and increased AMH levels and u/s measurement of increased antral follicle count (AFC) Secondary outcome: Improved ovarian response in IVF cycles if BAFs develop, and spontaneous or IVF pregnancy.

Official Title
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Does Subcutaneous Granulocyte Colony Stimulating Factor (G-CSF) Improve Ovarian Reserve in Women With Premature Ovarian Insufficiency?

Conditions
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Primary Ovarian Insufficiency, Premature Ovarian Failure

Intervention / Treatment
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* Drug: Neupogen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ages 25-40 Woman who meet criteria for POI defined as AFC < 5, AMH < 3 pmol/L and FSH >30 IU/L. There may also be associated symptoms of the menopause such as hot flushes, night sweats, insomnia and vaginal dryness. Women who are not taking any other medical or fertility treatments except natural estrogen to stop hot flushes. Those who are provided with informed consent. Exclusion Criteria: Women with age > 40 Women with history of autoimmune disorders Women with a history of hematopoietic cell malignancies Women with sickle cell disease Women with any other comorbidities that would preclude infertility treatment and pregnancy such as HIV/AIDS, hepatitis B or C, breast cancer or body mass index (BMI) >40.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with POI receiving G-CSF injections<br>Patients will receive 0.5 ml SC injections of G-CSF (Neupogen, Amgen, USA) at 300 micrograms/day for 4 consecutive days. The first injection will be administered in our office with a 60-minute observation period. Subsequent injections can be self-administered at home for three days, with a return to our clinic for monitoring the following day. This 4-day Neupogen regimen will be repeated in one month. Patients may undergo two rounds of G-CSF treatment one month apart. If no improvement is observed in gonadotropin, anti-Mullerian levels, and antral follicle count, a third treatment may be offered a month later. Follow-up includes blood assessment of AMH and FSH, as well as ultrasound measurement of basal antral follicle count for three months after the last G-CSF infusion. | Drug: Neupogen<br>* Subcutaneous injection of 0.5 ml of Neupogen at a concentration of 300 micrograms/day for 4 consecutive days<br>* Other names: Filgrastim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improving ovarian reserve markers | Success of the treatment will be assessed by a reduction in serum FSH, an increase in AMH (measure of ovarian reserve) and u/s measurement of an increased number of antral follicles (AFC). | It is anticipated within three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful Pregnancy | If an increased number of basal antral follicles is seen in association with an FSH level below 20 IU/L, the subjects will be offered a cycle of IVF to see if oocytes and subsequently embryos can be obtained. | It is anticipated within three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Filgrastim, Granulocyte colony stimulating factor, Premature Ovarian Insufficiency, Neupogen