scholarly journals FERTILITY PRESERVATION: Follicle reserve loss in ovarian tissue transplantation

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. F35-F44 ◽  
Author(s):  
Hadassa Roness ◽  
Dror Meirow
Keyword(s):  
Ovarian Function ◽  
Ovarian Tissue ◽  
Young Patients ◽  
Ovarian Tissue Cryopreservation ◽  
Ischemic Damage ◽  
Pharmacological Agents ◽  
Ovarian Tissue Transplantation ◽  
After Cancer ◽  
Tissue Cryopreservation ◽  
Follicle Activation

Ovarian tissue cryopreservation and transplantation (OTCP-TP) has progressed over the past decade from a revolutionary experimental procedure to a well-accepted treatment in many centers for young patients with a high risk of ovarian failure after cancer treatment. The procedure is remarkably successful, with studies reporting return of ovarian function in up to 95% of graft recipients and pregnancy rates of between 30 and 50%. The most significant limitation of OTCP-TP is the massive loss of follicles that occurs following transplantation, which is primarily attributed to ischemic damage and follicle activation. We review the current approaches to reducing follicle loss and maximizing graft lifespan via pharmacological agents which reduce ischemic damage and follicle activation. We further discuss the value and disadvantage of inducing follicle activation in the graft as a means of generating mature follicles in the immediate short term.

scholarly journals Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

2021 ◽  
Vol 11 ◽  
Author(s):  
Xia Hao ◽  
Amandine Anastácio ◽  
Laia Viñals-Ribé ◽  
Ana Santamaria Lacuesta ◽  
Christina Diakaki ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Young Patients ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Tissue Transplantation ◽  
Oocyte Competence ◽  
Patients With Cancer ◽  
Tissue Cryopreservation ◽  
Selection Of

Ovarian tissue cryopreservation is the only feasible method for fertility preservation in prepubertal girls that will undergo gonadotoxic chemotherapy. To date, the only clinical use of cryopreserved tissue is by a later tissue retransplantation to the patient. Clinical challenges in fertility preservation of very young patients with cancer include time constraints that do not allow to retrieve the tissue for cryopreservation before starting chemotherapy and the preclusion of future ovarian tissue transplantation due to the risk of reintroduction of malignant cells in patients with systemic diseases. To overcome these two challenges, we investigated using an experimental model the feasibility of retrieving secondary follicles from ovaries of prepubertal mice after cyclophosphamide (CPA) treatment in increasing doses of 50, 75, and 100 mg/kg. The follicles were thereafter cultured and matured in vitro. The main outcomes included the efficiency of the method in terms of obtained matured oocytes and the safety of these potentially fertility preservative procedures in terms of analyses of oocyte competence regarding normality of the spindle and chromosome configurations. Our findings demonstrated that it was feasible to isolate and culture secondary follicles and to obtain mature oocytes from prepubertal mice ovaries recently treated with CPA. The efficiency of this method was highly demonstrated in the 100 mg/kg CPA group, with near 90% follicle survival rate after 12 days’ culture, similarly to control. Around 80% of the follicles met the criteria to put into maturation, and more than 40% of them achieved metaphase II, with normal spindle and chromosome configurations observed. Suboptimal results were obtained in the 50 and 75 mg/kg CPA groups. These paradoxical findings towards CPA dose might probably reflect a more difficult selection of damaged growing follicles from ovaries recently treated with lower doses of CPA and a hampered ability to identify and discard those with reduced viability for the culture.

scholarly journals Hormonal Characteristics of Women Receiving Ovarian Tissue Transplantation with or without Endogenous Ovarian Activity

2021 ◽  
Vol 10 (22) ◽  
pp. 5217
Author(s):  
Vinnie Hornshøj Greve ◽  
Margit Dueholm ◽  
Linn Salto Mamsen ◽  
Stine Gry Kristensen ◽  
Erik Ernst ◽  
...  
Keyword(s):  
Detection Limit ◽  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Activity ◽  
Concomitant Increase ◽  
Ovarian Tissue Transplantation ◽  
Tissue Cryopreservation

Ovarian tissue cryopreservation (OTC) and transplantation of frozen/thawed ovarian tissue (OTT) are used for fertility preservation in girls and women. Here, we evaluated the hormonal characteristics of women with or without postmenopausal levels of FSH at the time of OTT to study differences and conditions that best support the initiation of ovarian function. A total of 74 women undergoing OTT (n = 51 with menopausal levels of FSH; n = 23 with premenopausal levels) were followed by measurements of FSH, LH, AMH, and oestradiol. Concentrations of FSH and LH returned to premenopausal levels after 20 weeks on average, with a concomitant increase in oestradiol. Despite resumption of ovarian activity, AMH concentrations were in most instances below the detection limit in the menopausal group, suggesting a low ovarian reserve. Despite a higher age in the premenopausal group, they more often experienced an AMH increase than the menopausal group, suggesting that conditions in the premenopausal ovary better sustain follicle survival, perhaps due to the higher concentrations of oestradiol. Collectively, this study highlights the need for improving follicle survival after OTT. Age and the amount of tissue transplanted are important factors that influence the ability to regain ovarian activity and levels of FSH may need to be downregulated and oestradiol increased prior to OTT.

scholarly journals Ovarian tissue freezing and activation after thawing: an update

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Li-fan Peng
Keyword(s):  
Granulosa Cells ◽  
Clinical Decision Making ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Clinical Decision ◽  
The Body ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Main Body ◽  
Tissue Cryopreservation

Abstract Background With the growth of women’s age, ovarian failure can be caused by various factors. For the women who need chemotherapy because of cancer factors, the preservation of fertility is more urgent. The treatment of cancer is also a process in which all tissues and organs of the body are severely damaged, especially in the reproductive system. Main body As a new fertility preservation technology, autologous ovarian tissue cryopreservation and transplantation is developing rapidly and showing great potentiality in preserving ovarian endocrine function of young cervical cancer patients. Vitrification and slow freezing are two common techniques applied for ovarian tissue cryopreservation. Thus, cryopreserved/thawed ovarian tissue and transplantation act as an important method to preserve ovarian function during radiotherapy and chemotherapy, and ovarian cryopreservation by vitrification is a very effective and extensively used method to cryopreserve ovaries. The morphology of oocytes and granulosa cells and the structure of organelles were observed under the microscope of histology; the hormone content in the stratified culture medium of granulosa cells with the diameter of follicle was used to evaluate the development potential of ovarian tissue, and finally the ovarian tissue stimulation was determined by the technique of ovarian tissue transplantation. Conclusions Although there are some limitations, the team members still carry out this review to provide some references and suggestions for clinical decision-making and further clinical research.

Spontaneous Pregnancy and Fertility Preservation Program in Women Undergoing High Dose Chemotherapy for Hematological Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1114-1114
Author(s):  
Izhar Hardan ◽  
Dror Meirow ◽  
Avichai Shimoni ◽  
Jacob Levron ◽  
Noga Shemtov ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Young Women ◽  
Ovarian Tissue ◽  
Young Patients ◽  
High Dose Chemotherapy ◽  
Ovarian Failure ◽  
Ovarian Tissue Cryopreservation ◽  
High Dose ◽  
Cryopreserved Ovarian Tissue ◽  
Tissue Cryopreservation

Abstract Loss of fertility is a major concern in young women undergoing high dose chemotherapy (HDT). Although it is generally accepted that therapy of the myeloabelative range is related with a high rate of fertility loss, we observed during the last years eight spontaneous pregnancies with normal deliveries in young women after bone marrow transplantation. Seven patients (pt’s) were with lymphoma and MM and were conditioned with BEAM regimen (n=6) and melphalan 200mg/sm (n=1) prior to an autologous SCT, while one patient had a secondary AML and underwent BEAM primed autologous SCT and Busulfex/FA primed allogeneic BMT. The median age at transplant of this group was 28y and median time from transplant to pregnancy was 25 months. More than 100 women of 18–40y.o were transplanted in our center during this period; however, obviously the fertility rate cannot be calculated as it is related with additional parameters including survival, post transplant complications and mainly patient’s preferences. Naturally we observed during the same period many young patients with ovarian failure post transplant, as well as one successful pregnancy from a cryopreserved embryo. Methods. We Therefore initiated in October 2000 a fertility preservation program in which all women of 18 – 40y.o were offered a pretransplant IVF with embryo preservation, and/or ovarian tissue cryopreservation (OTC), according to their clinical status. 651 pt’s were transplanted in our center in the last 44 months, of which 81 were women of 18–41y.o that were all enrolled in this program. Results. Seven pt’s of this group (8.6%) underwent IVF. The major causes of denying IVF were the need to delay BMT for more than clinically accepted, prolonged preexisting ovarian failure, lack of a suitable partner and patient’s preference. Seventeen pt’s (21%) underwent OTC. The major causes of denying OTC were patient’s preference (mainly due to no evidence of success with this method) and thrombocytopenia/neutropenia. During this period: One patient of this group was fertilized with her cryopreserved embryos 32 months after transplant and is at her 16 week of pregnancy. One patient underwent a successful transplantation of her cryopreserved ovarian tissue 2.5 years after HDC while in a documented ovarian failure, and gave birth to a healthy baby on June 2005. The OTC of this patient was performed after cis-platinum containing salvage therapy for relapsing NHL, prior to BEAM primed SCT, and immediately after a failure of hormonal stimulation for IVF. One patient underwent a cryopreserved ovarian tissue transplantation on July 2005 Conclusions: 1. Spontanous pregnancy after HDT, mainly at the younger age, is not a rare phenomenon. 2. Most young patients prior to HDT are not eligible for IVF. 3. Pretransplant ovarian tissue cryopreservation is a feasible tool in this set-up. The first success with this method is promising.

scholarly journals Female Fertility Preservation in Patients with Musculoskeletal Cancer

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 2
Author(s):  
D. Mihai ◽  
A. Velișcu ◽  
D. Comandașu ◽  
C. Coroleucă ◽  
C. Mehedințu ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Young Patients ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Premature Menopause ◽  
Musculoskeletal Tumor ◽  
Female Fertility Preservation ◽  
Tissue Cryopreservation

Abstract Introduction. Besides the improvement of the survival rate in young patients with musculoskeletal cancer, we should always consider that infertility and premature menopause due to treatment might dramatically affect their quality of life. Material and methods. This article is a review of literature. Results. After puberty, the first option should be ovarian controlled hyperstimulation (COS) resulting in oocytes that are consequently fertilized using FIV or ICSI and the cryopreservation of the embryos. If the patient does not have a partner at that moment, the next method is the vitrification of the oocytes resulting from the COS. The disadvantages of using COS are the need to postpone the radio and chemotherapy for at least 2-3 weeks and high oestradiol levels, but there are very few hormone dependent musculoskeletal tumors that may be affected. Ovarian tissue cryopreservation (OTC), with ovarian tissue transplantation (OTT) is the only method used if the patient is before puberty, plus, this technique allows patients to spontaneously conceive, if they do not have any other fertility pathology, but this freezing/ thawing procedure may have success or not. There is currently no evidence to suggest that OTT causes reseeding of the original cancer, and the restoring of the ovarian endocrine function was reported in about 95% of the cases. Conclusions. The success of fertility preservation techniques is related to the cryopreservation methods used and the age of the patient. The reproductive cells with the best survival are the embryos, the next are oocytes, or ovarian tissue may be cryopreserved. For best outcomes, the fertility preservation must be pluridisciplinary discussed, involving the ART specialist gynecologist, the oncologist and the surgeon of the musculoskeletal tumor.

scholarly journals FERTILITY PRESERVATION: Freezing of ovarian tissue and clinical opportunities

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. F27-F34 ◽  
Author(s):  
C Yding Andersen ◽  
L S Mamsen ◽  
S G Kristensen
Keyword(s):  
Fertility Preservation ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Genetic Diseases ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Insufficiency ◽  
Technical Aspects ◽  
Increased Risk ◽  
Tissue Cryopreservation

Ovarian tissue cryopreservation (OTC) is mainly used for fertility preservation in girls and women facing a gonadotoxic treatment. If the woman subsequently becomes menopausal, the ovarian tissue may be transplanted to regain ovarian function, including fertility. The method was developed more than two decades ago and today thousands of women worldwide have undergone OTC. Fewer than 500 patients have had tissue transplanted and close to 100% of those regain ovarian function. Several technical aspects of OTC are now becoming more established, including high quantitative follicle survival, defining the size of the tissue resulting in optimal tissue revascularisation and follicle loss resulting from transport of ovarian tissue prior to freezing. We have used OTC to safeguard fertility in patients with genetic diseases, which for some diagnoses is purely experimental, as no transplantations is yet been performed. Usage of OTC beyond fertility is now also being considered; here, the endocrine function of follicles is the focus. It has been suggested that ovarian tissue stored in the reproductive years may be used to avoid premature ovarian insufficiency (POI) when there is a familial disposition or to postpone menopause in patients with an increased risk of osteoporosis or cardiovascular diseases. The benefit of OTC beyond fertility requires, however, actual clinical studies. The current review includes several recent technical aspects with contributions from Denmark building on some of the early work by Roger Gosden.

Rat modeling of ovarian tissue cryopreservation and auto-grafting

2019 ◽  
Author(s):  
◽  
Tareq Mohamed Elhadi Lehmidi
Keyword(s):  
Ovarian Function ◽  
Ovarian Tissue ◽  
Autologous Transplantation ◽  
General Medicine ◽  
Human Reproduction ◽  
Ovarian Tissue Cryopreservation ◽  
University Of Missouri ◽  
Life Saving ◽  
The University ◽  
Tissue Cryopreservation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] New advancements in cancer treatment methods are increasing the survival rate of cancer patients. Unfortunately, these life-saving treatments, such as chemotherapy and radiotherapy, have permanent impacts on ovarian function leading to infertility, osteoporosis and obesity. Autologous transplantation of previously cryopreserved ovarian tissues would serve as a potential therapeutic approach in human reproduction and general medicine in terms of restoring steroid hormone function, fertility, body composition, and bone integrity.

scholarly journals Establishment of the ovarian tissue cryopreservation protocol on bovine model

2016 ◽  
Vol 19 (2) ◽  
pp. 24-32
Author(s):  
Dung Thi Phuong Nguyen ◽  
Lan Thi Thu Nguyen ◽  
Quang Nhat Nguyen ◽  
Tuong Manh Ho ◽  
Loc Minh Tai Nguyen ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Ovarian Tissue ◽  
Neutral Red ◽  
Slow Freezing ◽  
Ovarian Tissue Cryopreservation ◽  
Control Group ◽  
Ovarian Cortex ◽  
Group 2 ◽  
Tissue Cryopreservation ◽  
Cryopreservation Protocol

Ovarian tissue cryopreservation is a suitable method for fertility preservation on women receiving treatment that may threaten the ovarian function and subsequent fertility. The whole ovarian or a part of ovarian can be cryopreserved for future use. This study was aimed to establish ovarian tissue cryopreservation protocols on bovine model for human application in Vietnam. In this method, bovine ovarians were collected from a slaughterhouse and kept at 4 oC up to a maximum of 12 hours before doing experiments. The ovarian cortex was cut into pieces of 10x10x1 mm. These pieces were randomly divided into 3 groups: (1) fresh species (control group), (2) species were freezed by slow-freezing method and (3) pieces were freezed by vitrification. After thawing, ovarian cortex pieces were treated with Collagenase Ia for the follicle isolation. The isolated follicles then were stained with Neutral Red. The rate of viable follicles was used as the outcome measure to assess the efficiency of the cryopreservation protocol. In results, the rates of viable follicles were 72.46 ± 6.11 % and 59.09 ± 7.08 % after slow-freezing and vitrification comparing to the control group, respectively. This was the first study which successfully established a protocol of ovarian tissue cryopreservation on bovine model in Vietnam. The protocol should be improved for further application to human treatment in the near future.

scholarly journals The Effectiveness of Anti-Apoptotic Agents to Preserve Primordial Follicles and Prevent Tissue Damage during Ovarian Tissue Cryopreservation and Xenotransplantation

2021 ◽  
Vol 22 (5) ◽  
pp. 2534
Author(s):  
Sanghoon Lee ◽  
Hyun-Woong Cho ◽  
Boram Kim ◽  
Jae Kwan Lee ◽  
Tak Kim
Keyword(s):  
Tissue Damage ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Slow Freezing ◽  
Ovarian Tissue Cryopreservation ◽  
Second Step ◽  
Control Group ◽  
Dna Breaks ◽  
Primordial Follicles ◽  
Tissue Cryopreservation

The purpose of this study is to investigate the effectiveness of sphingosine-1-phosphate (S1P) and Z-VAD-FMK (Z-VAD) as anti-apoptotic agents to preserve ovarian function and prevent tissue damage during ovarian tissue cryopreservation and transplantation. This study consisted of two steps, in vitro and in vivo. In the first step, human ovarian tissues were cryopreserved using slow-freezing media alone, S1P, or Z-VAD (control, S1P, Z-VAD group); based on the outcomes in these groups, Z-VAD was selected for subsequent xenotransplantation. In the second step, human frozen/thawed ovarian tissues were grafted into fifty mice divided into three groups: slow-freezing/thawing and transplantation without an anti-apoptotic agent (Trans-control) and xenotransplantation with or without Z-VAD injection (Trans-Z-VAD-positive and Trams-Z-VAD-negative groups, respectively). In the first step, the Z-VAD group had a significantly higher primordial follicular count than the S1P (p = 0.005) and control groups (p = 0.04). Transplanted ovarian tissues were obtained 4 weeks after transplantation (second step). Angiogenesis was significantly increased in the Z-VAD-negative (p = 0.03) and -positive (p = 0.04) groups compared to the control group. This study demonstrated that slow-freezing and transplantation with Z-VAD is an effective method for preserving primordial follicle counts, decreasing double-strand DNA breaks, and increasing angiogenesis in a mouse model. Further molecular and clinical studies are needed to confirm these results.

P–456 Impact of first-line chemotherapy prior to ovarian tissue cryopreservation on primordial follicle activation and survival in pre-pubertal and young adult patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Devos ◽  
P Dia. Vidal ◽  
E Anckaert ◽  
M M Dolmans ◽  
I Demeestere
Keyword(s):  
Signaling Pathways ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Tunel Staining ◽  
First Line ◽  
Chemotherapeutic Regimen ◽  
The Impact ◽  
Tissue Cryopreservation ◽  
Line Chemotherapy ◽  
Follicle Activation

Abstract Study question How does chemotherapeutic regimen administered prior to ovarian tissue cryopreservation affect the signaling pathways regulating ovarian reserve and follicular survival in pre-pubertal and adult patients? Summary answer Chemotherapy induces key signaling processes of follicle activation and increases apoptosis in quiescent follicle. However, damages were different according to the age of the patient. What is known already Therapeutic regimen can damage the ovarian reserve leading to infertility of cancer survivors. Among fertility preservation options, cortical tissue banking appears to be an attractive alternative for patients who cannot delay their treatment or have already started chemotherapy. Though previous studies showed that first-line chemotherapy may induce follicular damages, the impact on follicle activation signaling pathways in human remains poorly understood. Deciphering the signaling modifications under chemotherapy is critical to have a better understanding of the follicle depletion process. Moreover, only few studies on cryopreserved tissue were conducted in children whereas follicle distribution differs compared to post-pubertal women. Study design, size, duration Cryopreserved ovarian tissue from young adult (16–27 years old, n = 6) and pre-pubertal (3–10 years old, n = 6) cancer patients were used as model. Fragments were thawed and cultured for 24 hours after size homogenization (4x2x0.5 mm). Patients who received chemotherapy before ovarian tissue cryopreservation were compared to non-exposed patients. PI3K/AKT/mTOR and Hippo pathways, as well as follicles and stroma survival, were assessed among the different groups at thawing and after culture. Participants/materials, setting, methods The impact of previous chemotherapy exposure on follicle activation, on the PI3K/AKT/mTOR and Hippo pathways was assessed at thawing and after 24 hours of culture by protein analyses (immunostaining and western blot). Histological analyses (follicular counting, immunostaining and TUNEL staining) were performed at the two timepoints to assess follicle distribution, morphology, stroma structure and apoptosis. Main results and the role of chance: The damage of chemotherapeutic regimen prior to cryopreservation was observed specifically on quiescent follicles after thawing by TUNEL staining in both adult and pre-pubertal patients. Surprisingly, apoptosis occurred more specifically in oocytes of pre-pubertal treated tissue while adult treated patients showed granulosa cells death. After culture, apoptosis was observed in the stroma but healthy follicles were observed in all conditions. Atretic follicles were observed similarly in pre-pubertal and adult cortex previously exposed to chemotherapy while not in the unexposed tissue. Protein analyses showed a higher expression of PI3K and Hippo proteins among all groups at thawing compared to cultured groups while difference was observed between pre-pubertal and adult cortex. At thawing, cortical tissues previously exposed to chemotherapy had a higher expression of phosphorylated forms of AKT and RPS6 compared to untreated groups, irrespective to the age. Moreover, immunostainings showed an oocyte-specific localization of p-AKT while p-RPS6 was more pronounced in the granulosa cells, suggesting an early process of follicle activation. Limitations, reasons for caution This study was limited to the evaluation of two major signaling pathways, PI3K/AKT/mTOR and Hippo. Moreover, considering the scarcity and the heterogeneity of our model, the number of patients included in this study is limited and the results should be interpreted with caution. Wider implications of the findings: Our results highlight the involvement of age and previous chemotherapeutic treatment in the regulation of signaling pathways regulating follicular activation, growth, and survival. Besides sustaining the chemotherapy-induced “burn out effect” theory, it opens perspectives to regulate the deleterious impacts of chemotherapy on follicles though molecular control of the altered pathways. Trial registration number Not applicable

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