Maturation of Follicles After Transplantation of Ovarian Tissue Into the Pelvic Wall and the Ovary

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the pelvic wall or the ovary represents a better location for the maturation of follicles in the context of ovarian transplantation after cryopreservation of ovarian tissue before cytotoxic therapies.

Detailed Description
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The development of modern medicine made it more likely for oncological patients to survive. Also, there are a lot of young female patients with a persistent wish for kids. After an aggressive chemotherapy, premature ovarian failure (POF) is a possible consequence of the therapy. Therefore, efficient fertility protective interventions are requested. The transplantation of ovarian tissue after cryopreservation is a valuable method, which could remain fertility after POF induced by cytotoxic therapies. Especially for girls suffering from cancer, who didn't reach puberty yet, cryopreservation of ovarian tissue is the only opportunity to preserve a chance of restoring fertility after POF. There are two locations, which could be used for the retransplantation of the cryopreserved tissue: the remaining ovary and the pelvic wall. Both, the ovary and the subperitoneal pocket in the pelvic wall present a location, where the maturation of follicles is possible. The remaining question is: where do more follicles grow? To answer this question, a study will be necessary. The purpose of this study is to determine whether the pelvic wall or the ovary represents a better location for the maturation of follicles in the context of ovarian transplantation after cryopreservation of ovarian tissue before cytotoxic therapies. Interventions: Ovarian tissue will be transplanted into two different locations; subperitoneal into the loge of the adnexa of uterus and contralateral into the ovary. The assignment of the two parts of ovarian tissue to the place of transplantation (pelvic wall vs. ovary) will be randomised. The study-specific interventions include: Transplantation of the same amount of ovarian tissue into both locations Monthly sonographic controls and determination of estradiol, LH, FSH and progesterone from the 3rd on to the 12th month after the transplantation. Therefore, blood samples will be made. Monthly documentation of the duration of the cycle from the 3rd on to the 12th month after transplantation One year after the transplantation, the investigators will be able to determine which location is more likely to grow follicles. With the gained knowledge, standardized recommendations could be formulated which help to improve the whole process of medical care of female oncologist patients.

Official Title
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Transplantation of Ovarian Tissue Into the Pelvic Wall and the Ovary After Cryopreservation of Ovarian Tissue Before Cytotoxic Therapies - Where do More Follicles Grow?

Conditions
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Infertility, Ovarian Failure, Premature

Intervention / Treatment
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* Other: Transplantation into pelvic wall
* Other: Transplantation into the ovary


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at cryopreservation ot tissue max. 38 years Age at transplantation 18-49 years At least one maintained ovary Premature ovarian failure Indication for an autologous transplantation of ovarian tissue Permitted pregnancy from the part of the oncologists Written informed consent Exclusion Criteria: Age at transplantation <18 and >49 years Cryopreservation in the context of a leucaemia, neuroblastoma, Burkitt-lymphoma Important: Inclusion is only done by one of the recruiting centers. Study participation will only be given on invitation. Please contact Principal Investigator!

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transplantation into pelvic wall<br>Ovarian transplantation into the pelvic wall after cryopreservation of ovarian tissue before cytotoxic therapies | Other: Transplantation into pelvic wall<br>* Ovarian tissue will be transplanted subperitoneal into the loge of the adnexa of Uterus.<br>|
| Active Comparator: Transplantation into the ovary<br>Ovarian transplantation into ovary after cryopreservation of ovarian tissue before cytotoxic therapies | Other: Transplantation into the ovary<br>* Ovarian tissue will be transplanted contralateral into the ovary.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of follicle maturation in transplanted tissue between pelvic wall and ovary | The participants will get an assessment of the follicle maturation on both sides (pelvic wall and ovary) each month beginning 3 months after the transplantation until 12 months after the transplantation. Overall, 10 assessments will take place. The maturation of follicles will be detected with sonography and measured in mm. Along with the sonography, blood samples will be taken and examined for their amount of estradiol, FSH and progesterone. A follicle ≥15mm with a concentration of estradiol >500 pmol/L (>136pg/ml) is considered a mature follicle. The primary outcome contains the quantitative comparison of mature follicles grown on both sides. | Beginning 3 months after the transplantation until 12 months after the transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of cycle, measured in weeks | The participants will be asked for the duration of their last cycle (2, 3, 4, 5, 6, 7, 8 weeks or no cycle). The assessments will take place monthly, beginning 3 months after the transplantation until 12 months after the transplantation. | Beginning 3 months after the transplantation until 12 months after the transplantation | 
| Number of study participants with pregnancy | Documentation of pregnancy ratio after transplantation of autologous ovarian tissue | 12 months after transplantation and 24 months after transplantation | 
| Number of study participants with life-birth after pregnancy | Documentation of life-birth ratio after pregnancy in context after transplantation of autologous ovarian tissue | 12 months after transplantation and 24 months after transplantation | 
| Determination of hormone levels after transplantation, concerning the concentration of estradiol, progesterone, LH, FSH | Blood samples will be examined for their amount of estradiol, progesterone, FSH and LH in order to check the vitality and the functionality of the transplanted tissue. | Beginning 3 months after the transplantation until 12 months after the transplantation | 
| Sonographic measurement of the endometrium wall, measured in mm | Monthly sonographic measurement of the endometrium wall will be performed. Along with the determination of hormone levels after the transplantation, these measurements hold a more detailed evaluation of the activity of the transplanted tissue and his effect on a functional organ (e.g. endometrium). | Beginning 3 months after the transplantation until 12 months after the transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Ovarian Failure, Premature, Ovarian Follicle, Ovary, Tissue Transplantation, Cryopreservation, Pelvis, Chemotherapy, Pregnancy Rate, Folliculogenesis, Endometrium, Estrogens, Progestins, Follicle Stimulating Hormone, Estradiol, Progesterone, Hormones, Maturation of Follicles, Pregnant Women, Premature Menopause, Ovarian Insufficiency, Ovarian Insufficiency, Premature, Cytotoxic therapy, Fertility Protection, Reproductive Medicine, Reproductive Techniques, Reproductive Technology, Cryotherapy, Pregnancy