Ovarian Tissue Transplantation Research Articles

Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation—A Systematic Review

Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation—A Systematic Review

Novel Approaches Used for Decreasing Apoptosis Rate in Ovarian Tissue Cryopreservation and Transplantation

Apoptosis is the main cause of atresia in ovarian follicles. In oxidative stress (OS) conditions, an imbalance between pro-apoptotic and anti-apoptotic genes can increase the apoptosis rate. In some diseases, such as cancers, patients lose fertility due to chemotherapy and radiotherapy. One way to maintain fertility in these patients is ovarian tissue cryopreservation and transplantation (OTC/T). Studies show that OTC/T also increases apoptosis due to hypoxia and ischemia but fortunately new findings show that applying new approaches could decrease apoptosis in these procedures considerably. This article reviewed follicular atresia, apoptosis during cryopreservation and transplantation, and factors affecting the reduction of apoptosis.

Resolving candidate genes of duck ovarian tissue transplantation via RNA-Seq and expression network analyses

This study aims to identify candidate genes related to ovarian development after ovarian tissue transplantation through transcriptome sequencing (RNA-seq) and expression network analyses, as well as to provide a reference for determining the molecular mechanism of improving ovarian development following ovarian tissue transplantation. We collected ovarian tissues from 15 thirty-day-old ducks and split each ovary into 4 equal portions of comparable sizes before orthotopically transplanting them into 2-day-old ducks. Samples were collected on days 0 (untransplanted), 3, 6, and 9. The samples were paraffin sectioned and then subjected to Hematoxylin-Eosin (HE) staining and follicular counting. We extracted RNA from ovarian samples via the Trizol method to construct a transcriptome library, which was then sequenced by the Illumina Novaseq 6000 sequencing platform. The sequencing results were examined for differentially expressed genes (DEG) through gene ontology (GO) function and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set enrichment analysis (GSEA), weighted correlation network analysis (WGCNA), and protein-protein interaction (PPI) networks. Some of the candidate genes were selected for verification using real-time fluorescence quantitative PCR (qRT-PCR). Histological analysis revealed a significant reduction in the number of morphologically normal follicles at 3, 6, and 9 d after ovarian transplantation, along with significantly higher abnormality rates (P < 0.05). The transcriptome analysis results revealed 2,114, 2,224, and 2,257 upregulated DEGs and 2,647, 2,883, and 2,665 downregulated DEGs at 3, 6, and 9 d after ovarian transplantation, respectively. Enrichment analysis revealed the involvement multiple pathways in inflammatory signaling, signal transduction, and cellular processes. Furthermore, WGCNA yielded 13 modules, with 10, 4, and 6 candidate genes mined at 3, 6 and 9 d after ovarian transplantation, respectively. Transcription factor (TF) prediction showed that STAT1 was the most important TF. Finally, the qRT-PCR verification results revealed that 12 candidate genes exhibited an expression trend consistent with sequencing data. In summary, significant differences were observed in the number of follicles in duck ovaries following ovarian transplantation. Candidate genes involved in ovarian vascular remodeling and proliferation were screened using RNA-Seq and WGCNA.

Current Fertility Preservation Steps in Young Women Suffering from Cancer and Future Perspectives.

Childhood cancer incidence, especially in high-income countries, has led to a focus on preserving fertility in this vulnerable population. The common treatments, such as radiation and certain chemotherapeutic agents, though effective, pose a risk to fertility. For adult women, established techniques like embryo and egg freezing are standard, requiring ovarian stimulation. However, for prepubescent girls, ovarian tissue freezing has become the primary option, eliminating the need for hormonal preparation. This review describes the beginning, evolution, and current situation of the fertility preservation options for this young population. A total of 75 studies were included, covering the steps in the current fertility preservation protocols: (i) ovarian tissue extraction, (ii) the freezing method, and (iii) thawing and transplantation. Cryopreservation and the subsequent transplantation of ovarian tissue have resulted in successful fertility restoration, with over 200 recorded live births, including cases involving ovarian tissue cryopreserved from prepubescent girls. Despite promising results, challenges persist, such as follicular loss during transplantation, which is attributed to ischemic and oxidative damage. Optimizing ovarian tissue-freezing processes and exploring alternatives to transplantation, like in vitro systems for follicles to establish maturation, are essential to mitigating associated risks. Further research is required in fertility preservation techniques to enhance clinical outcomes in the future. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications, and risks, which can be an important tool in terms of preserving fertility in younger women.

Optimal human ovarian follicle isolation: A review focused on enzymatic digestion.

The damage or depletion of ovarian reserves due to aging or cancer treatment can increase the need for fertility preservation techniques. One of the most common ways of supporting fertility in prepubertal girls and women who require immediate cancer treatment is through ovarian tissue cryopreservation and re-transplantation following cancer treatment. However, a more appropriate method should be employed in diseases such as leukemia, where malignant cells may be present in cryopreserved tissue, instead of ovarian tissue transplantation. Human ovarian follicle isolation for in vitro culture or the use of artificial ovaries for their growth can decrease the risk of reintroducing cancer cells into these individuals. Here we review the methods for the isolation of human ovarian follicles.

Restoring Ovarian Fertility and Hormone Function: Recent Advancements, Ongoing Efforts and Future Applications.

The last 20 years have seen substantial improvements in fertility and hormone preservation and restoration technologies for a growing number of cancer survivors. However, further advancements are required to fill the gaps for those who cannot use current technologies or to improve the efficacy and longevity of current fertility and hormone restoration technologies. Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) offers those unable to undergo ovarian stimulation for egg retrieval and cryopreservation an option that restores both fertility and hormone function. However, those with metastatic disease in their ovaries are unable to transplant this tissue. Therefore, new technologies to produce good-quality eggs and restore long-term cyclic ovarian function are being investigated and developed to expand options for a variety of patients. This mini-review describes current and near future technologies including in vitro maturation, in vitro follicle growth and maturation, bioprosthetic ovaries, and stem cell applications in fertility restoration research by their proximity to clinical application.

A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24IU/L in examination before OTC. FSH was greater than 10.0IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58min, and the average blood loss was 32.1 ± 41.6mL. The maximum blood loss was 200mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20days and began HSCT within 30days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3years after HSCT and resumed regular menstruation 6months after OTT. Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Research progress on mechanism of follicle injury after frozen ovarian tissue transplantation and protective strategies.

The iatrogenic ovarian dysfunction caused by cancer treatment have been increasing, along with the age at onset of malignant tumors getting younger, the survival of cancer patients being longer, as well as the delayed childbearing age for females; therefore it becomes a major clinical challenge to preserve the fertility of these patients. Ovarian tissue cryopreservation is the only solution for female cancer patients in prepubertal ages and those who cannot delay gonadotoxic therapy. However, the successful rate of cryopreservation and transplantation of ovarian tissue is still low at present due to the risk of ischemia and hypoxia of grafted tissues. Abnormal activation of primordial follicle and ischemia-reperfusion injury after blood supply recovery also cause massive loss of follicles in grafted ovarian tissues. It has been tried in various studies to reduce the damage of follicles during freezing and transplantation by adding certain drugs, and extend the duration of endocrine and reproductive function in patients with ovarian transplantation. For example, melatonin, N-acetylcysteine, erythropoietin or other antioxidants are used to reduce oxidative stress; mesenchymal stem cells derived from different tissues, basic fibroblast growth factor, vascular endothelial growth factor, angiopoietin 2 and gonadotropin are used to promote revascularization; anti-Müllerian hormone and rapamycin are used to reduce abnormal activation of primordial follicles. This article reviews the research progress on the main mechanisms of follicle loss after ovarian tissue transplantation, including hypoxia, ischemia-reperfusion injury and associated cell death, and abnormal activation of follicles; and explores the methods of reducing graft follicle loss to provide reference for improving the efficiency of ovarian tissue cryopreservation and transplantation.

65 Testing the effects of rigid encapsulations on bovine primordial follicle quiescence versus growth

OBJECTIVES/GOALS: There is an interest in developing a bioprosthetic ovary for ovarian tissue transplantation. The properties of the ovarian extracellular matrix need to be better understood in order to replicate the human ovary. We tested the effects of an encapsulating hydrogel at different rigidities on bovine primordial follicle activation, growth, and survival. METHODS/STUDY POPULATION: Bovine primordial follicles were isolated from ovarian cortex. A mean of 9.9 follicles (range 3-24) were encapsulated per bead in either 1% or 5 % alginate across 4 experiments. The encapsulated follicles were subsequently crosslinked in a calcium sulfate solution. Follicles were then cultured for 8 days with light microscopy imaging taken every other day along with media exchanges. Follicles were then examined using immunofluorescence. Growth and survival curves were constructed and all statistical analyses were performed using Graph Pad Prism 9. RESULTS/ANTICIPATED RESULTS: A total of 372 follicles were encapsulated across 32 beads (16 in 1% alginate and 16 in 5% alginate). There were no differences in initial follicle size between the two conditions (33.53 µm vs. 32.45 µm, p=0.47). At the end of 8 days, there was no difference between follicle size (59.55 vs. 56.06, p=0.48). Additionally, there was no difference in survival between 1% and 5% alginate encapsulation (57.75% vs. 52.43%. p=0.40). Immunofluorescence is being performed on encapsulated follicles to confirm the presence of DDX4, a molecular marker of oocytes, after 8 days in culture. Additional encapsulated follicles have also been submitted for histologic sectioning and hematoxylin and eosin staining to better characterize the viability and health of these follicles after 8 days in culture. DISCUSSION/SIGNIFICANCE: There was no significant difference in growth or survival between primordial follicles cultured in 1% or 5% alginate gels. Immunofluorescent analysis confirmed the presence of viable follicles at the end of 8 days of culture. Future work needs to further explore how factors in the ovarian extracellular matrix impact follicle maintenance and growth.

Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation.

Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.

The role of the indoleamine 2,3-dioxygenase gene in preventing ovarian transplant rejection in rats.

Indoleamine 2, 3-dioxygenase (IDO) plays important roles in maternal immune tolerance. Female Sprague Dawley rats (9-11weeks old) were randomly divided into an autoplastic transplantation group (n = 75) and an allograft transplantation group (n = 300) further divided into subgroups of ovarian transplantation, allograft ovarian transplantation, allograft ovarian transplantation with cyclosporine A treatment, allograft ovarian transplantation and transfection with IDO-expressing lentiviruses, and allograft ovarian transplantation and transfection with control lentiviruses. IDO was successfully transfected intothe transplanted ovarian tissue. The survival rate, success rate of ovarian transplantation, period until estrous cycle restoration, and estrogen levels of rats that received IDO-expressing lentiviruseswere significantly different from those of rats that underwent allograft transplantation and with control transfection (all P < 0.05), but not significantly different from those of rats that received autoplastic transplantation (all P > 0.05). The number of ovarian follicles in the transplanted ovarian tissue of rats that received IDO-expressing lentiviruses was also significantly higher. The expression level of IDO protein detected by immunohistochemistry and western blotting was especially high in ovaries that had received IDO-containing lentiviruses. Naturally pregnant rats were found in each group postoperatively. These results indicate that IDO-expressing lentiviruses were successfully transfected into transplanted ovarian tissues of rats and that IDO was stably expressed within a certain time. These findings suggest that the expression level of IDO protein is associated with an enhanced success rate of ovarian tissue transplantation and a short restoration period of endocrine function.

Restauration of hormonal function after ovarian tissue transplantation: French legal aspects

Restauration of hormonal function after ovarian tissue transplantation: French legal aspects

Ovarian tissue cryopreservation for fertility preservation before hematopoietic stem cell transplantation in patients with sickle cell disease: safety, ovarian function follow-up, and results of ovarian tissue transplantation.

To describe the experience of performing ovarian tissue cryopreservation (OTC) before hematopoietic stem cell transplantation (HSCT), among girls/women with severe sickle cell disease (SCD)(SS or S/β0-thalassemia) who are, besides the usual surgical risk, at risk of SCD-related complications during the fertility preservation procedure for improving their counseling and management. This retrospective study included 75 patients (girls/women) with SCD who have had OTC before myeloablative conditioning regimen (MAC) for HSCT. Characteristics of patients and data on OTC, ovarian status follow-up, and results of ovarian tissue transplantation (OTT) were collected in medical records. At OTC, the median (IQR 25-75; range) age of the patients was 9.6 (6.9-14.1; 3.6-28.3) years, 56/75 were prepubertal, and no SCD or surgery-related complications occurred. The median follow-up post-HSCT was > 9years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6months post-HSCT and we do not have ovarian function follow-up for the other 2 patients. All the remaining patients (n = 15) had POI. Five patients had OTT. All had a return of ovarian function. One patient gave birth to a healthy baby. OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.

Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys.

To clarify the reproductive outcomes of fertility preservation (FP) treatment. We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation

Ovarian tissue cryopreservation has been proven to preserve fertility against gonadotoxic treatments. It has not been clear how this procedure would perform if planned for slowing ovarian aging. This study aimed to determine the feasibility of cryopreserving ovarian tissue to extend reproductive life span and delay menopause by autotransplantation near menopause. Based on the existing biological data on follicle loss rates, a stochastic model of primordial follicle wastage was developed to determine the years of delay in menopause (denoted by D) by ovarian tissue cryopreservation and transplantation near menopause. Our model accounted for (1) age at ovarian tissue harvest (21-40 years), (2) the amount of ovarian cortex harvested, (3) transplantation of harvested tissues in single vs multiple procedures (fractionation), and (4) posttransplant follicle survival (40% [conservative] vs 80% [improved] vs 100% [ideal or hypothetical]). Our model predicted that, for most women aged <40 years, ovarian tissue cryopreservation and transplantation would result in a significant delay in menopause. The advantage is greater if the follicle loss after transplant can be minimized. As an example, the delay in menopause (D) for a woman with a median ovarian reserve who cryopreserves 25% of her ovarian cortex at the age of 25 years and for whom 40% of follicles survive after transplantation would be approximately 11.8 years, but this extends to 15.5 years if the survival is 80%. As another novel finding, spreading the same amount of tissue to repetitive transplants significantly extends the benefit. For example, for the same 25-year-old woman with a median ovarian reserve, 25% cortex removal, and 40% follicle survival, fractionating the transplants to 3 or 6 procedures would result in the corresponding delay in menopause (D) of 23 or 31 years. The same conditions (3 or 6 procedures) would delay menopause as much as 47 years if posttransplant follicle survival is improved to 80% with modern approaches. An interactive Web tool was created to test all variables and the feasibility of ovarian tissue freezing and transplantation to delay ovarian aging (here). Our model predicts that with harvesting at earlier adult ages and better transplant techniques, a significant menopause postponement and, potentially, fertile life span extension can be achieved by ovarian tissue cryopreservation and transplantation in healthy women.

Current Position of Oncofertility in Adolescent Female Cancer Patients: A Comparative Review on Society Guidelines.

Fertility preservation (FP) in pediatric and adolescent oncology patients presents a complex interplay between cancer treatment imperatives and reproductive aspirations, demanding a multi-disciplinary approach. Essential guidelines emphasize the importance of early referrals to FP specialists, ensuring timely counseling on oocyte and ovarian tissue cryopreservation options. Proper patient selection and risk assessment, considering intrinsic and extrinsic factors, is crucial for judicious resource utilization and optimal outcomes. Gonadotoxic effects of cancer treatments pose significant threats to reproductive capabilities. Oocyte cryopreservation (OC) is preferred in post-pubertal adolescents without partners. Cultural and religious concerns, especially regarding hymenal integrity, influence FP decisions, necessitating culturally sensitive consent processes. Ovarian tissue cryopreservation (OTC) offers an alternative for those unfit for OC. Despite its experimental label in some societies, emerging data support the efficacy of OTC, with ovarian tissue transplantation (OTT) showing promise in restoring ovarian function. However, the reintroduction of potentially malignant cells during transplantation remains a concern. Overall, while FP offers hope for future parenthood, the intricacies of decision-making and the potential medical, ethical, and cultural challenges underscore the importance of a personalized, multi-disciplinary approach. In this review, guidelines from various societies have been comprehensively reviewed and analyzed to provide insight into the clinical practice of oncofertility.

Comparative effects of a calcium chelator (BAPTA-AM) and melatonin on cryopreservation-induced oxidative stress and damage in ovarian tissue

Oncology treatments cause infertility, and ovarian tissue cryopreservation and transplantation (OTCT) is the only option for fertility preservation in prepubertal girls with cancer. However, OTCT is associated with massive follicle loss. Here, we aimed to determine the effect of supplementation of slow freezing and vitrification media with BAPTA-AM and melatonin alone and in combination on ovarian tissue viability, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), and follicular morphology and viability. Our results indicated that BAPTA-AM and melatonin can significantly improve ovarian tissue viability and the TAC/ROS ratio and reduce ROS generation in frozen-thawed ovarian tissues in slow freezing and vitrification procedures. BAPTA-AM was also found to be less effective on TAC compared to melatonin in vitrified ovarian tissue. While supplementation of slow freezing and vitrification media with BAPTA-AM and/or melatonin could increase the percentage of morphologically intact follicles in cryopreserved ovarian tissues, the differences were not significant. In conclusion, supplementation of cryopreservation media with BAPTA-AM or melatonin improved the outcome of ovarian tissue cryopreservation in both vitrification and slow freezing methods. Our data provide some insight into the importance of modulating redox balance and intracellular Ca2+ levels during ovarian tissue cryopreservation to optimize the current cryopreservation methods.

The Clinical Application of Platelet-Rich Plasma in the Female Reproductive System: A Narrative Review.

Platelet-rich plasma is an autologous plasma containing platelets prepared from fresh whole blood drawn from a peripheral vein. Through processing, it can be prepared to contain supraphysiologic levels of platelets at three to five times greater than the level of normal plasma. PRP has been explored both in vivo and ex vivo in the human endometrium model in its ability to harness the intrinsic regenerative capacity of the endometrium. Intrauterine autologous PRP infusions have been shown to increase endometrial thickness and reduce the rate of intrauterine adhesions. In the setting of recurrent implantation failure, intrauterine infusion of PRP has been shown to increase clinical pregnancy rate. PRP also appears to hold a potential role in select patients with premature ovarian insufficiency, poor ovarian responders and in improving outcomes following frozen-thawed transplantation of autologous ovarian tissue. Further studies are required to explore the potential role of PRP in reproductive medicine further, to help standardise PRP protocols and evaluate which routes of administration are most effective.

Management of Menopause Towards Natural Management Without Hormones

Background: Formerly, the life expectancy of women was around the third decade, preserving their ovarian function; With technological development, better socioeconomic and health conditions, they currently live until the ninth decade of life; with a third or more after menopause; with the risk that this entails due to chronic non-communicable diseases associated with hormonal deficiency; It has been suggested that transplantation of cryopreserved ovarian tissue in reproductive life, implanted at menopause, would restore ovarian activity after menopause. Methodology: To obtain the information, a bibliographic review was carried out in the electronic databases of Google and PubMed-Medline. Articles in English were reviewed between the years 2015 and 2023, with the combination of English terms MeSH: Ovarian tissue cryopreservation and transplantation in menopause. Results: 59 articles were located, of which 32 were excluded as they were considered not appropriate for the specific topic of the review. 27 articles were selected, including originals, prospective studies and reviews. Conclusions: Ovarian tissue transplantation could become the anti-aging therapy by restoring long-term ovarian endocrine function; However, more evidence is required to achieve and promote the health of women in menopause.

Primary ovarian insufficiency- An overview: Part 2 diagnosis and management

Loss of normal ovarian function before the age of 40 characterizes primary ovarian insufficiency (POI), sometimes called premature ovarian failure or early menopause. Many women all around the globe deal with this serious reproductive health issue. The purpose of this study is to provide a broad perspective on how to identify and treat primary ovarian insufficiency. Clinical symptoms, hormone profiles, and ovarian imaging all play a role in making a diagnosis of POI. Genetic predisposition, autoimmune disease, and medical intervention are all possible origins. Counseling and treatment techniques for afflicted women can only be used when a timely and correct diagnosis has been made. Hormone replacement treatment (HRT) for symptom alleviation, avoidance of long-term consequences including osteoporosis and cardiovascular disease, and preservation of fertility are all part of the management of postmenopausal irritability (POI). To reduce the severity of menopausal symptoms and safeguard bone health, oestrogen replacement treatment is needed. HRT selection should be patient-specific, taking into account factors like as age, co-morbidities, and individual preferences. If a young woman is diagnosed with POI and she wants to have children in the future, she and her doctor should talk about fertility preservation strategies such oocyte or ovarian tissue cryopreservation. The latest treatments and possible revolutionary methods to POI management are also discussed in this overview. Stem cell therapy, ovarian tissue transplantation, and hormone manipulation are all examples of such unproven methods. While these treatments are still in their infancy, they show promise for the future of POI management. In conclusion, this review article gives a comprehensive, up-to-date explanation of how primary ovarian insufficiency is diagnosed and treated. Early detection, proper counselling, and individualised treatment plans are emphasised for afflicted females. The reproductive and overall health results of these people may be improved with a deeper knowledge of the processes producing POI and the development of more effective medicines.