| Eligibility |
Inclusion Criteria:
- Able to understand and communicate in English language
- Female of age 18-43 years
- Diagnosis of premature ovarian insufficiency based on ESHRE Guidelines (i)
oligo/amenorrhea for at least 4 months, and (ii) an elevated FSH level >25 IU/L on two
occasions >4 weeks apart, or diagnosis of low ovarian reserve defined as: Basal FSH
value >10 IU/L or failure of prior attempts of assisted reproductive techniques due to
limited ovarian response (poor responders)
- Normal karyotype 46, XX, and no known history FMR1 premutation (fragile X syndrome)
- Baseline AMH levels = 1.0 ng/mL
- Presence of at least one ovary
- Normal uterine anatomy (by any clinically and/or imaging acceptable methods)
- Normal thyroid function as evident by normal serum Thyroid Stimulating Hormone (TSH)
levels
- For subjects who had contraception before, the duration of amenorrhea should be more
than 3 months after discontinuation of the oral contraception pill (OCP) or more than
6 months after discontinuation of Depo Provera (or similar) therapies
- Agree to report any pregnancy to the research staff immediately
- Willing and able to comply with study requirements and follow up instructions
- Patient with known history of endometriosis or polycystic ovarian syndrome
- If subject is planning to pursue pregnancy: presence of at least unilateral tubal
patency (with any clinically acceptable methods)
Exclusion Criteria:
- Currently pregnant or breast-feeding
- Has a history of, or evidence of current gynecologic malignancy, breast cancer or
other estrogen responsive cancer or any other malignancy within the past five years
- Subjects with FMR1 premutation (fragile X syndrome), a BMP15 mutation or family
history of a first degree relative with POI
- Presence of adnexal masses indicating the need for further evaluation
- Major mental health disorder that precludes participation in the study
- Active substance abuse or dependence
- Current or recent (within the past 2 weeks) use of the following medications: Oral or
systemic corticosteroids, Hormones (estrogen, progestin, oral contraceptives),
Danazol, anticoagulants, herbal or botanical supplements with possible hormonal
effects. Washout will be allowed (2 weeks from screening)
- Subjects under hormonal treatments including hormone replacement therapy (HRT) for
osteoporosis, cardiovascular disease, or recalcitrant vasomotor symptomatology within
3 months from screening
- Subjects with a history of breast cancer or other estrogen responsive cancer within 5
years from screening
- Subjects with existing malignant neoplasm, under active management for malignant
neoplasm or under active surveillance for malignant neoplasm within 5 years from
screening
- Subjects with history of thromboembolic events such as pulmonary embolism, stroke, or
ischemic heart disease
- Subjects with uncontrolled hypertension, kidney disease, liver disease, or polycystic
ovary syndrome (PCOS) as defined below:
- Uncontrolled hypertension: Systolic BP = 140 and/or Diastolic BP =90 in patients
taking anti-hypertensive treatment
- Kidney Disease: an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73
m^2 (Incase the result is above/below acceptable range, one repeat test is
acceptable)
- Liver Disease: Serum aminotransferase (ALT or AST) levels > 2x ULN
- PCOS criteria: Oligo-anovulation (Irregular periods), antral follicle count (AFC)
>12 measuring 2-9mm, hyperandrogenism (elevated testosterone and DHEA levels),
clinical hirsutism
- Subjects with untreated endocrinopathies including Cushing's disease, thyroid disease,
congenital adrenal hyperplasia and hyperprolactinemia
- Subjects with intra-uterine devices (IUDs)
- Subjects who are allergic to low-molecular-weight heparin sodium or human albumin
- Medical conditions that are contraindicated in pregnancy
- Type I or Type II diabetes mellitus, or if receiving antidiabetic medications within 3
months from screening
- Known anemia (Hemoglobin < 11 g/dL)
- History of deep venous thrombosis, and/or pulmonary embolus
- History of cerebrovascular disease
- History of contrast media allergy
- Known heart disease (New York Heart Association Class II or higher)
- Known Liver disease (defined as Aspartate Aminotransferase (AST) or Alanine
Aminotransferase (ALT) >2 times normal, or total bilirubin >2.5mg/dL)
- Known Renal disease (defined as Blood urea nitrogen (BUN) >30 mg/dL or serum
creatinine > 1.6 mg/dL)
|
