In vitro maturation of primordial follicles after cryopreservation of human ovarian tissue: Problems remain

2002 ◽  
Vol 38 (3) ◽  
pp. 153-157 ◽  
Author(s):  
Raffaella Depalo ◽  
Giuseppe Loverro ◽  
Luigi Selvaggi
Keyword(s):  
In Vitro Maturation ◽  
Ovarian Tissue ◽  
Primordial Follicles ◽  
Human Ovarian Tissue

scholarly journals Fertility Preservation in Women With Malignancy: Future Endeavors

2019 ◽  
Vol 13 ◽  
pp. 117955811987249 ◽  
Author(s):  
Zeev Blumenfeld
Keyword(s):  
Fertility Preservation ◽  
In Vitro Maturation ◽  
Ovarian Tissue ◽  
Gnrh Analogues ◽  
Primordial Follicles ◽  
Artificial Ovary ◽  
Pros And Cons ◽  
The Subject ◽  
Far Future

The area of fertility preservation is constantly developing. To date, the only noninvestigational and unequivocally accepted methods for fertility preservation are cryopreservation of embryos and unfertilized oocytes. This article is one of several in a monogram on fertility preservation. The debate, pros and cons, and equivocal data on the use of GnRH analogues for fertility preservation are elaborated by 3 other manuscripts, in this monogram. A repeat of the arguments, pros and cons of this debatable issue, would be a repetition and redundancy of what is already included in this monogram. The subject of ovarian cryopreservation for fertility preservation is also elaborated by several other authors in this monogram. It is possible that, in the not too far future, the technologies of in vitro maturation of primordial follicles to metaphase 2 oocytes, and the “artificial ovary,” will turn clinically available. These technologies may bypass the risk of resuming malignancy by autotransplantation of cryopreserved-thawed ovarian tissue in leukemia and diseases where malignant cells may persist in the cryopreserved ovarian tissue. We summarize here the suggested options for future endeavors in fertility preservation.

scholarly journals THE CURRENT STATE OF THE PROBLEM OF FEMALE FERTILITY IN CANCER AND A DECREASE IN OVARIAN RESERVE

2019 ◽  
Vol 5 (2) ◽  
pp. 18-33
Author(s):  
A. A. Shmidt ◽  
O. N. Kharkevich ◽  
L. I. Kalyuzhnaya
Keyword(s):  
Ovarian Reserve ◽  
In Vitro Maturation ◽  
Ovarian Tissue ◽  
The Body ◽  
Female Fertility ◽  
Primordial Follicles ◽  
Advantages And Disadvantages ◽  
Current State ◽  
Number Of Patients

Analysis of the current state of the problem of preserving female fertility in cancer and reducing ovarian reserve revealed that there are currently several proven methods for young women — cryopreservation of embryos, oocytes and ovarian tissue, each of which has its own advantages and disadvantages. The promising technologies are cryopreservation of oocytes after in vitro maturation, as well as cryopreservation of embryos derived from oocytes, which were matured in vitro. In vitro maturation of immature oocytes aspirated from primordial follicles allows for the production of many mature oocytes without ovarian stimulation, which makes this technology a potentially effective strategy for preserving fertility. However, the best results can be achieved by combining several methods that must be determined individually in each specific case. Although there was no negative effect of cancer on the results of treatment of oncological obesity in the next generation, long-term observations and studies with a large number of patients are needed. The goal of helping with oncological infertility is not only the preservation of fertility, but the creation of a nationwide system of care for oncological diseases in which interdisciplinary coordination will allow all cancer patients to receive multidisciplinary assistance. The organization and standardization of the treatment of oncological symptoms and the development of modern technologies for preserving the reserve of female fertility outside the body are the urgent tasks of national health care in our country.

A new in vitro model for pre-transplantation diagnosis of frozen/thawed human ovarian tissue

2011 ◽  
Vol 71 (05) ◽  
Author(s):  
M Salama ◽  
K Winkler ◽  
KF Murach ◽  
S Hofer ◽  
L Wildt ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Ovarian Tissue ◽  
Human Ovarian Tissue ◽  
Vitro Model

In-vitro maturation of oocytes from ovarian tissue expands fertility preservation options

2011 ◽  
Vol 96 (3) ◽  
pp. S49
Author(s):  
L. Clark ◽  
W. Vitek ◽  
J. Witmyer ◽  
R. Hackett ◽  
S.A. Carson ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
In Vitro Maturation ◽  
Ovarian Tissue

P–431 Human oocytes in-vitro maturation efficacy from infancy to adulthood – is there an optimal age?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Karavani ◽  
P Wasserzug-Pash ◽  
T Mordechai-Daniel ◽  
M Klutstein ◽  
T Imbar
Keyword(s):  
Fertility Preservation ◽  
In Vitro Maturation ◽  
Ovarian Tissue ◽  
Age Groups ◽  
Ovarian Tissue Cryopreservation ◽  
Success Rates ◽  
Human Oocytes ◽  
Tertiary Center ◽  
Significant Difference

Abstract Study question Does human oocytes in-vitro maturation (IVM) effectiveness change throughout childhood, adolescence and adulthood in girls and women undergoing fertility preservation via ovarian tissue cryopreservation (OTC) prior to chemo-radiotherapy exposure? Summary answer The optimal age for IVM is from menarche to 25 years, while pre-menarche girls and women older than 30 years have extremely low maturation rates. What is known already In vitro maturation of oocytes from antral follicles seen during tissue harvesting is a fertility preservation technique with potential advantages over OTC, as mature frozen and later thawed oocyte used for fertilization poses decreased risk of malignant cells re-seeding, as compared to ovarian tissue implantation. We previously demonstrated that IVM performed following OTC in fertility preservation patients, even in pre-menarche girls, yields a fair amount of oocytes available for IVM and freezing for future use. Study design, size, duration A retrospective cohort study, evaluating IVM outcomes in chemotherapy naïve patients referred for fertility preservation by OTC that had oocyte collected from the medium with attempted IVM between 2003 and 2020 in a university affiliated tertiary center. Participants/materials, setting, methods A total of 133 chemotherapy naïve patients aged 1–35 years with attempted IVM were included in the study. The primary outcome was IVM rate in the different age groups – pre-menarche (1–5 years and ≥6 years), post-menarche (menarche–17 years), young adults (18–24 years) and adults (25–29 and 30–35 years). Comparison between paired groups for significant difference in the IVM rate parameter was done using the Tukey’s Studentized Range (HSD) Test. Main results and the role of chance A gradual increase in mean IVM rate was demonstrated in the age groups over 1 to 25 years (4.6% (1–5 years), 23.8% (6 years to menarche) and 28.4% (menarche to 17 years), with a peak of 38.3% in the 18–24 years group, followed by a decrease in the 25–29 years group (19.3%), down to a very low IVM rate (8.9%) in the 30–35 years group. A significant difference in IVM rates was noted between the age extremes – the very young (1–5 years) and the oldest (30–35 years) groups, as compared with the 18–24-year group (p < 0.001). Number of oocytes matured, percent of patients with matured oocytes and overall maturation rate differed significantly (p < 0.001). Limitations, reasons for caution Data regarding ovarian reserve evaluation was not available for most of the patients, due to our pre-op OTC procedures protocol. None of our patients have used their frozen in-vitro matured oocytes, as such further implications of age on in-vitro matured oocytes quality and implantation potential has yet to be evaluated. Wider implications of the findings: Our finding of extremely low success rates in those very young (under 6 years) and older (≥30 years) patients suggest that IVM of oocyte retrieved during OTC prior to chemotherapy should not be attempted in these age group. Trial registration number N/A

scholarly journals In-vitro fragmentation of ovarian tissue activates primordial follicles through the Hippo pathway

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
C De Roo ◽  
S Lierman ◽  
K Tilleman ◽  
P De Sutter
Keyword(s):  
Tissue Culture ◽  
Ovarian Tissue ◽  
Hippo Pathway ◽  
Primordial Follicle ◽  
Akt Pathway ◽  
Primordial Follicles ◽  
Primordial Follicle Activation ◽  
The Hippo Pathway ◽  
Follicle Activation

Abstract STUDY QUESTION What is the role of the Hippo and PI3K/Akt pathway in follicles during ovarian tissue culture in tissue derived from oncological patients and transgender men? SUMMARY ANSWER Results highlight a Hippo pathway driven primordial follicle activation in vitro, predominantly from Day 0 to Day 4. WHAT IS KNOWN ALREADY In-vitro ovarian tissue culture aims at activating and maturing primordial follicles for fertility restoration in patients with a threatened ovarian reserve. Not all patients are eligible for ovarian cortex transplantation and therefore several groups are attempting to culture ovarian tissue in-vitro. Cortex fragmentation disrupts the Hippo pathway, leading to increased expression of downstream growth factors and follicle growth. The PI3K/Akt pathway is considered the intracellular pathway to where different extracellular factors involved in primordial follicle activation in-vivo converge. In order to optimise current ovarian tissue culture models, information on progression of these pathways during tissue culture is mandatory. STUDY DESIGN, SIZE, DURATION The first step of a multistep cortex culture system was performed using 144 ovarian cortex pieces from a total of six patients. Per patient, 24 cortical strips were cultured for 6 days and six pieces per patient were collected for downstream analysis of follicle development and Hippo and PI3K/Akt pathway targets every second day. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian tissue was obtained from oncological (N = 3; 28.67 ± 4.51 years) and transgender (N = 3; 23.33 ± 1.53 years) patients. Follicles were analysed using haematoxylin-eosin staining and pathways were studied using immunohistochemistry and precise follicle excision by laser capture micro-dissection for RT-qPCR analysis. MIQE guidelines for RT-qPCR were pursued. Reference gene selection (GAPDH, RPL3A, 18s rRNA) was performed using GeNorm Reference Gene Selection Kit. Statistical analysis was conducted with IBM SPSS Statistics 23 (Poisson regression, negative binomial regression, ANOVA and paired t-test). MAIN RESULTS AND THE ROLE OF CHANCE Immunohistochemical analysis confirmed a Hippo pathway driven primordial follicle activation due to mechanical manipulation of the cortical strips. Ovarian tissue preparation and culture induced the inhibitory phosphorylated Yes-associated protein (pYAP) to disappear in granulosa cells of primordial follicles on Day 2. The stimulatory YAP on the contrary appeared in primordial granulosa cells over increasing culture days. Looking at the YAP target connective tissue growth factor (CTGF), a significantly up-regulated CTGF was noted in primordial follicles when comparing Day 2 and Day 4 (ratio Day 2/4 = 0.082; P < 0.05), clearly showing an effect on the Hippo pathway in primordial follicles during tissue culture. Follicle classification showed a significant drop in estimated primordial follicle counts in the oncological cohort (−78%; P = 0.021) on Day 2 and in the transgender cohort on Day 4 (−634%; P = 0.008). Intermediate follicle counts showed a non-significant increasing trend to during culture and this follicle recruitment and growth resulted in a significant rise in estimated primary follicle counts on Day 6 in oncological patients (170%; P = 0.025) and, although limited in absolute numbers, a significant increase in secondary follicles on Day 4 (367%; P = 0.021) in the transgender cohort. Subsequent antral follicle development could not be observed. LIMITATIONS, REASONS FOR CAUTION A limitation is the small sample size, inherent to this study subject, especially as a large amount of tissue was needed per patient to reduce inter-patient variation in different downstream analysis techniques. A particular and specific weakness of this study is the inability to include an age-matched control group. WIDER IMPLICATIONS OF THE FINDINGS These findings support an adapted tissue preparation for Hippo pathway disruption and a shorter first phase of tissue culture. This work may also have implications for transplantation of cryopreserved tissue as larger strips (and thus slower burnout due to less Hippo pathway disruption) could be a benefit. STUDY FUNDING/COMPETING INTEREST(S) This research was financially supported by the Foundation Against Cancer (Stichting tegen Kanker, TBMT001816N), the Flemish Foundation of Scientific Research (FWO Vlaanderen, FWO G0.065.11N10) and the Gender Identity Research and Education Society (GIRES) foundation. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

Slush nitrogen vitrification of human ovarian tissue does not alter gene expression and improves follicle health and progression in long-term in vitro culture

2018 ◽  
Vol 110 (7) ◽  
pp. 1356-1366 ◽  
Author(s):  
Vincenza Barbato ◽  
Roberto Gualtieri ◽  
Teresa Capriglione ◽  
Maria Michela Pallotta ◽  
Sabrina Braun ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Vitro Culture ◽  
Ovarian Tissue ◽  
Human Ovarian Tissue

scholarly journals In vitro follicle culture in the context of IVF

Reproduction ◽  
2018 ◽  
Vol 156 (1) ◽  
pp. F59-F73 ◽  
Author(s):  
Anamaria C Herta ◽  
Francesca Lolicato ◽  
Johan E J Smitz
Keyword(s):  
Fertility Preservation ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Primordial Follicle ◽  
Assisted Reproduction Techniques ◽  
Realistic Potential ◽  
Primordial Follicles ◽  
Primordial Follicle Activation ◽  
Extracellular Matrix Components

The currently available assisted reproduction techniques for fertility preservation (i.e.in vitromaturation (IVM) andin vitrofertilization) are insufficient as stand-alone procedures as only few reproductive cells can be conserved with these techniques. Oocytes in primordial follicles are well suited to survive the cryopreservation procedure and of use as valuable starting material for fertilization, on the condition that these could be grown up to fully matured oocytes. Our understanding of the biological mechanisms directing primordial follicle activation has increased over the last years and this knowledge has paved the way toward clinical applications. New multistepin vitrosystems are making use of purified precursor cells and extracellular matrix components and by applying bio-printing technologies, an adequate follicular niche can be built. IVM of human oocytes is clinically applied in patients with polycystic ovary/polycystic ovary syndrome; related knowhow could become useful for fertility preservation and for patients with maturation failure and follicle-stimulating hormone resistance. The expectations from the research on human ovarian tissue and immature oocytes cultures, in combination with the improved vitrification methods, are high as these technologies can offer realistic potential for fertility preservation.

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