Use of Simvastatin, Fibrin Clots, and Their Combination to Improve Human Ovarian Tissue Grafting for Fertility Restoration After Anti-Cancer Therapy.

Anticancer treatments, particularly chemotherapy, induce ovarian damage and loss of ovarian follicles. There are limited options for fertility restoration, one of which is pre-chemotherapy cryopreservation of ovarian tissue. Transplantation of frozen-thawed human ovarian tissue from cancer survivors has resulted in live-births.

Novel extra cellular-like matrices to improve human ovarian grafting.

Purpose: To investigate if human ovarian grafting with pure virgin human recombinant collagen type-1 from bioengineered plant lines (CollPlant™) or small intestine submucosa (SIS) yields better implantation results for human ovarian tissue and which method benefits more when combined with the host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A.

Methods: Human ovarian tissue wrapped in CollPlant or SIS was transplanted into immunodeficient mice with/without host/graft treatment. The tissue was assessed by follicle counts (including atretic), for apoptosis evaluation by terminal deoxynucleotidyl transferase assay and for immunohistochemical evaluation of neovascularization by platelet endothelial cell adhesion molecule (PECAM) expression, and for identification of proliferating granulosa cells by Ki67 expression.

The influence of in vivo exposure to nonylphenol ethoxylate 10 (NP-10) on the ovarian reserve in a mouse model.

Aim: To determine the effect of nonylphenol-ethoxylate-10 (NP-10) on the ovarian reserve in a mouse model.

Design: Female mice were maintained on purified water or exposed to NP-10 from 3-7-weeks of age. At 7-weeks they were stimulated, mated and the zygotes were cultured in-vitro.

Premature ovarian aging in carriers: a prototype of systemic precocious aging?

Purpose: Though former evidence implies a correlation of breast cancer susceptibility gene () mutation with reduced ovarian reserve, the data is yet inconsistent. Our aim was to investigate biomarkers of ovarian aging in a cohort of young healthy carriers of the mutation. We hypothesized that the role played by genes in aging pathways is not exclusive to the ovary.

Female fertility preservation: past, present and future.

Anti-cancer therapy, particularly chemotherapy, damages ovarian follicles and promotes ovarian failure. The only pharmacological means for protecting the ovaries from chemotherapy-induced injury is gonadotrophin-releasing hormone agonist, but its efficiency remains controversial; ovarian transposition is used to shield the ovary from radiation when indicated. Until the late 1990s, the only option for fertility preservation and restoration in women with cancer was embryo cryopreservation.

[LAPAROSCOPICALLY-ASSISTED ULTRASOUND-GUIDED PERCUTANEOUS TRANSABDOMINAL OOCYTE COLLECTION: FERTILITY PRESERVATION IN A 17-YEARS-OLD GIRL WITH VAGINAL EWING SARCOMA].

Options for preserving fertility in children and adolescents with cancer depend on patient age, the available time frame, and the treatment regimen. Ovarian stimulation with mature oocyte preservation is often the optimal method in post-menarcheal adolescents. We describe a case of a 17-year-old girl with vaginal soft-tissue Ewing sarcoma in whom transvaginal oocyte collection for fertility preservation was ruled out by the large tumor.

[FERTILITY PRESERVATION IN YOUNG CANCER PATIENTS - CAN WE OPTIMIZE THE PATH?].

Introduction: Advances in cancer therapy have improved the long-term survival of cancer patients. Concerns about fertility represent a major issue for young cancer patients. The emergent discipline of oncofertility, an intersection between oncology and fertility, is a new concept that describes an integrated network of clinical resources that focus on fertility preservation from both clinical and research perspectives.

Attempts to improve human ovarian transplantation outcomes of needle-immersed vitrification and slow-freezing by host and graft treatments.

Purpose: To investigate if needle-immersed vitrification or slow-freezing yields better implantation results for human ovarian tissue and which method benefits more when combined with the "improvement protocol" of host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A.

Methods: Human ovarian tissue was preserved by needle-immersed vitrification or slow-freezing and transplanted into immunodeficient mice, either untreated (groups A and C, respectively) or treated with the improvement protocol (groups B and D, respectively). Grafted and ungrafted slices were evaluated by follicle counts, apoptosis assay and immunohistochemistry for Ki67 and platelet endothelial cell adhesion molecule (PECAM).

Extracellular-like matrices and leukaemia inhibitory factor for in vitro culture of human primordial follicles.

The possibility of maturing human primordial follicles in vitro would assist fertility restoration without the danger of reseeding malignancies. Leukaemia inhibitory factor (LIF) and certain culture matrices may promote human follicular growth. The present study compared human primordial follicular growth on novel culture matrices, namely human recombinant vitronectin (hrVit), small intestine submucosa (SIS), alginate scaffolds and human recombinant virgin collagen bioengineered in tobacco plant lines (CollPlant).

Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro.

How chemotherapy affects dormant ovarian primordial follicles is unclear. The 'burnout' theory, studied only in mice, suggests cyclophosphamide enhances primordial follicle activation. Using 4-hydroperoxycyclophosphamide (4hc) and phosphoramide mustard (PM), this study assessed how the active cyclophosphamide metabolites 4-hydroxycyclophosphamide (4-OHC) and PM, affect human primordial follicles.

Aspiration of immature oocytes during cesarean section for fertility preservation.

Background: In vitro maturation (IVM) of immature oocytes is an important technology for selected clinical indications. We previously described a pregnant woman with a history of renal transplantation who underwent oocyte aspiration during cesarean section (CS) for fertility preservation and future surrogacy.

Case: A 27-year-old pregnant woman was diagnosed with neck rhabdomyosarcoma at 37 weeks' gestation.

Ovarian minimal residual disease in chronic myeloid leukaemia.

The options for fertility preservation include cryopreservation of ovarian tissue. Although transplantation of cryopreserved-thawed ovarian tissue in cancer survivors has resulted in live births, there is evidence of malignancy involvement in ovarian tissue, especially in leukaemia. The objectives of this study were to investigate the involvement of chronic myeloid leukaemia (CML) in ovaries by both pathological/immunohistochemical methods and PCR for the identification of the Philadelphia chromosome (BCR-ABL transcripts).

Attempted application of bioengineered/biosynthetic supporting matrices with phosphatidylinositol-trisphosphate-enhancing substances to organ culture of human primordial follicles.

Purpose: To improve human primordial follicle culture.

Methods: Thin or thick ovarian slices were cultured on alginate scaffolds or in PEG-fibrinogen hydrogels with or without bpV (pic), which prevents the conversion of phosphatidylinositol-trisphosphate (PIP3) to phosphatidylinositol-bisphosphate (PIP2) or 740Y-P which converts PIP2 to PIP3. Follicular growth was evaluated by follicular counts, Ki67 immunohistochemistry, and 17β-estradiol (E2) levels.

Fibroblast growth factor 10 in human ovaries.

The expression of fibroblast growth factor 10 (FGF-10) has not been studied in human ovarian cortical follicles. The aim of the present study was to investigate the expression of FGF-10 in preantral follicles from fetuses, girls and women. Ovarian samples were obtained from 14 human fetuses at 21-33 gestational weeks and from 35 girls and women aged 5-39 years.

Vasoactive intestinal peptide and its receptors in human ovarian cortical follicles.

Background: Ovarian cryopreservation is one option for fertility preservation in patients with cancer. The danger of reseeding malignancies could be eliminated by in vitro maturation of primordial follicles from the frozen-thawed tissue. However, the development of this system is hindered by uncertainties regarding factors that activate primordial follicles.

Possible improvements in human ovarian grafting by various host and graft treatments.

Background: Anticancer treatment poses a high risk of ovarian failure. In many cases cryopreservation of ovarian tissue is the only option for fertility preservation. Although autologous transplantation of cryopreserved-thawed ovarian tissue has resulted in live births, slow graft revascularization and ischemia after transplantation leads to substantial follicular loss.

Alginate scaffold for organ culture of cryopreserved-thawed human ovarian cortical follicles.

Purpose: To compare macroporous alginate scaffolds with Matrigel for culturing frozen-thawed human primordial follicles in organ culture.

Methods: Twelve girls/women donated ovarian tissue. One tissue sample was fixed immediately after thawing (uncultured samples).

Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9.

Context: The signals initiating growth of primordial follicles are unknown. Bone morphogenetic protein 15 (BMP15) and growth differentiating factor 9 (GDF9) are promising candidates.

Objective: The objective of the study was to evaluate for the first time the effects of human recombinant BMP15 and human recombinant GDF9 on the in vitro development of human primordial follicles.

Invited commentary: a single nucleotide polymorphism in BMP15 is associated with high response to controlled ovarian hyperstimulation.

A report has been published which shows a connection between single nucleotide polymorphisms (SNP) in the bone morphogenetic protein 15 (BMP15) gene and ovarian hyperstimulation syndrome (OHSS) in women, similar to reported effects of heterozygous BMP15 point mutations in sheep. The report also describes the near-significant presence of another BMP15 gene SNP correlated with a low response to ovarian stimulation. Previous studies associated two SNP with anovulation or infertility in women with polycystic ovary syndrome, and heterozygosity for another BMP15 SNP resulted in ovarian dysgenesis and hypergonadotrophic failure.

Expression of neurotrophin 3 and its tropomyosin-related kinase receptor C in human preantral follicles.

Objective: To investigate the expression of neurotrophin 3 (NT3) and its receptor tropomyosin-related kinase C (TrkC) in human preantral follicles. Neurotrophins appear to play important roles in preantral follicles. Data on ovarian NT3 and its receptor TrkC are sparse in humans.

WITHDRAWN: Bone Morphogenetic Protein 15 (BMP15)/Growth Differentiating Factor 9 Heterodimer Is More Potent than BMP15 Alone in in Vitro Activation of Human Primordial Follicles.

This manuscript was withdrawn at the request of the authors.

Improving posttransplantation survival of human ovarian tissue by treating the host and graft.

Objective: To improve posttransplantation survival of frozen-thawed human ovarian tissue in immunodeficient mice.

Design: Histologic study of transplanted human ovaries after treating the host and graft.

Setting: Infertility unit, university-affiliated tertiary medical center.