Autologous Ovarian Tissue Transplantation

This investigation involves patient enrollment, thaw and surgical transplantation of
previously collected cryopreserved ovarian cortical tissue, a series of follow-up assessments
during the first 2 years after transplantation and an annual survey after year 2.

Screening visit (standard fertility consultation):

1. The subject will complete a medical and reproductive history to document menstrual
function and suitability for pregnancy.

2. The subject will have standard fertility testing (including but not limited to serum
Follicle Stimulating Hormone (FSH), Estradiol (E2), and Anti-Mullerian Hormone (AMH),
luteinizing hormone (LH), testosterone and progesterone).

3. Vaginal ultrasound will be performed for measures of ovarian volume and antral follicle
counts.

4. A pregnancy test will be performed to rule out pregnancy.

5. Each potential subject will undergo a comprehensive fertility consult including
counseling regarding the extent to which participation in this study might be of
ultimate benefit. Alternatives to participation include: continuing to try to conceive
on her own, use of donor oocytes or embryos, or adoption.

6. The subject will have to obtain clearance from her oncologist and will be counseled by a
reproductive endocrinologist to determine whether she is healthy enough to consider
pregnancy and to discuss the potential risks and benefits of the study.

Visit #1 - pre-op visit (can be combined with initial screening visit):

Eligible subjects will be consented by the study physician and complete the same infectious
disease testing as was performed at the time of ovarian tissue freezing (including but not
limited to HIV 1&2, HTLV 1&2, Hepatitis B, Hepatitis C, syphilis, chlamydia, gonorrhea, CMV,
West Nile virus). The subjects will also complete Fertility quality of life survey
(FertiQoL). FertiQoL is a validated measure of quality of life in people experiencing
fertility problems.

Only after confirming eligibility, obtaining informed consent and completing baseline
measures, ovarian tissue thawing and transplantation will be performed.

Visit #2 - Ovarian tissue transplantation:

At the time of ovarian tissue thawing, an outpatient laparoscopy (or minilaparotomy if the
patient is not deemed to be a good candidate for laparoscopic surgery) will be performed
under general anesthesia. Ovarian cortical tissue will be transplanted within the pelvis
according to the most effective available techniques.

Visit #3: Post-operative assessment:

Within six weeks of transplant, a postoperative follow-up assessment will be conducted to
ensure adequate patient recovery and emotional well-being. Blood tests (including but not
limited to serum FSH, E2, and AMH, LH, testosterone and progesterone), pelvic ultrasound and
FertiQoL survey, will be conducted to assess reproductive hormone levels, menstrual function,
complications from surgery, pregnancy, medical and medication history, and cancer relapse.
Referral to the clinical counselor may be made, if indicated.

Visits #4, #5, #6, #7 and #8 at 3, 6, 9, 12 and 24 months post-op:

A series of 5 additional follow-up assessments will be conducted during the first 2 years
after transplant with Reproductive Endocrinology and Infertility to assess reproductive
hormone levels, menstrual function, complications from surgery, pregnancy, changes in medical
and medication status, and cancer relapse. A visit may be added at the time menstruation is
restored if this occurs between regularly scheduled visits. At each follow up visit hormone
testing is performed, vaginal ultrasound and FertiQoL survey will be administered. Additional
clinical follow-up and testing may be determined in consultation with the subject's
oncologist.

Annual Survey:

Starting year 3 post-transplantation, each subject will be surveyed annually. The survey is
voluntary and confidential and will be conducted by scripted phone interview or
self-administered survey through secure email. The survey will include questions about
menstrual/pregnancy history, new diagnoses or treatments, and feelings about participating in
the study. Detailed information about pregnancy and birth outcomes will be collected by a
combination of survey and chart review. Outcome data including remission, relapse or death,
will be collected. Contact information will also be updated.

Inclusion Criteria:

- Previously cryopreserved ovarian tissue

- Ovarian insufficency

- Good health

- Candidate for pregnancy

- Oncologist's clearance

Exclusion Criteria:

- Patients considered to be high risk for surgical complications

- Women with contraindication for pregnancy

- Women positive for the BRCA mutations

- Women with a history of leukemia, ovarian cancer or a cancer that likely involved
ovaries at the time of ovarian tissue collection

- Women with psychological, psychiatric, or other conditions which prevent giving fully
informed consent

- Current pregnancy