New Insights on In Vitro Maturation of Oocytes for Fertility Preservation.

In the last decade, the evolution of oncofertility has sparked a resurgence of interest in in vitro maturation (IVM) due to its suitability in certain oncological scenarios where controlled ovarian hyperstimulation may not be feasible. The retrieval of immature cumulus-oocyte complexes from small antral follicles, regardless of the menstrual cycle phase, presents a swift opportunity to vitrify mature oocytes or embryos post-IVM in urgent situations or when stimulation is not advisable. Harvesting immature cumulus-oocyte complexes and immature oocytes can be achieved transvaginally or directly in the laboratory from extracorporeal ovarian tissue. Although IVM has transitioned from an experimental status due to safety validations, it relies on the intricate process of oocyte maturation. Despite successful live births resulting from IVM in fertility preservation contexts, the comparatively lower developmental competence of in vitro matured oocytes highlights the necessity to enhance IVM culture systems. Recent advancements in IVM systems hold promise in bolstering oocyte competence post-IVM, thereby narrowing the gap between IVM and outcomes from ovarian stimulation. Additionally, for optimizing the chances of conception in cancer survivors, the combination of IVM and ovarian tissue cryopreservation stands as the favored choice when ovarian stimulation is unfeasible.

Oocyte vitrification for fertility preservation following COS does not delay the initiation of neoadjuvant chemotherapy for breast cancer compared to IVM.

PURPOSE: The objective of the present study was to evaluate whether oocyte vitrification following controlled ovarian stimulation (COS) for fertility preservation (FP) delays the initiation of neoadjuvant chemotherapy (NAC) for breast cancer (BC) as compared to in vitro maturation (IVM). METHODS: We performed a retrospective cohort study including all BC patients eligible for oocyte vitrification following COS or in vitro maturation (IVM) before initiation of NAC between January 2016 and December 2020. The inclusion criteria were female patients aged between 18 and 40, with confirmed non metastatic BC, with indication of NAC, who have had oocyte retrieval for FP after COS, or IVM + / - cryopreservation of ovarian tissue (OTC). Various time points related to cancer diagnosis, FP, or chemotherapy were obtained from a medical record review. RESULTS: A total of 197 patients with confirmed BC who had oocyte retrieval following COS (n = 57) or IVM + / - OTC (n = 140) for FP prior to NAC were included. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COS or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36. 8 ± 13.5 days; p = 0.89). CONCLUSIONS: The indication of NAC for BC should not be considered as an impediment to urgent COS for oocyte vitrification for FP.

Anti-Mullerian Hormone Assessment in Assisted Reproductive Technique Outcome and Natural Conception.

In recent years, the prevalence of infertility has increased, and appears to affect approximately one in six couples. Some of them must perform assisted reproductive techniques (ART) in order to achieve pregnancy. As a result, growing interest has arisen about predictive factors of pregnancy and live birth with and without ART. Anti-Mullerian hormone (AMH) is a glycoprotein discovered in the 1950s in male embryonic sexual differentiation. Later, in 1984, its role in folliculogenesis was reported: secreted by granulosa cells, this hormone is involved in the regulation of the recruitment of primordial follicles and in follicular growth. AMH assays were developed for women in 1990s, and the serum AMH level has rapidly become a crucial element in managing women's fertility. Based mainly on its ability to be a quantitative but indirect marker of ovarian reserve, the serum AMH assay is widely used in reproductive medicine and ART. This review summarizes current knowledge of the AMH assessment in the field of reproductive medicine. We focus on the role of AMH level to predict spontaneous pregnancy occurrence, ART outcomes, and fertility preservation outcomes.

Chemotherapy and female fertility.

Chemotherapy to treat cancer is usually responsible for early ovarian follicle depletion. Ovarian damage induced by cancer treatments frequently results in infertility in surviving patients of childbearing age. Several fertility preservation techniques have been developed. Nowadays, oocyte or embryo cryopreservation with or without ovarian stimulation and cryopreservation of the ovarian cortex are the most commonly used. However, these methods may be difficult to implement in some situations, and subsequent use of the cryopreserved germ cells remains uncertain, with no guarantee of pregnancy. Improved knowledge of the molecular mechanisms and signaling pathways involved in chemotherapy-induced ovarian damage is therefore necessary, to develop new strategies for fertility preservation. The effects of various chemotherapies have been studied in animal models or in vitro on ovarian cultures, suggesting various mechanisms of gonadotoxicity. Today the challenge is to develop molecules and techniques to limit the negative impact of chemotherapy on the ovaries, using experimental models, especially in animals. In this review, the various theories concerning ovarian damage induced by chemotherapy will be reviewed and emerging approaches for ovarian protection will be explained.

Changes in the Key Odorants and Aroma Profiles of Hamlin and Valencia Orange Juices Not from Concentrate (NFC) during Chilled Storage.

Application of the aroma extract dilution analysis (AEDA) on the volatiles isolated by extraction/SAFE distillation from NFC (not from concentrate) juice from Hamlin oranges revealed 51 odor-active constituents in the flavor dilution (FD) factor range of 8 to 8192 among which vanillin, wine lactone, and ( R)-linalool appeared with the highest FD factors. The AEDA applied on the volatile fraction of the same batch of juice stored at 0 °C for 10 months under aseptic conditions showed clear changes in the aroma profile as well as in the FD factors of key odorants. The reduction in the intensity of the citrus-like, pungent, green odor attributes in the aroma profile correlated with the loss of 1-penten-3-one, acetaldehyde, and ( Z)-3-hexenal and a clear decrease in hexanal, octanal, nonanal, decanal, and ( E, E)-2,4-decadienal. Quantitation done by stabile isotope dilution assays followed by a calculation of odor activity values (ratio of concentration to odor thresholds in citrate buffer) confirmed that the quick loss of 1-penten-3-one and acetaldehyde already within a few weeks and a significant reduction in nearly all aldehydes over the storage time of 10 months were responsible for the changes in the overall aroma profile of the juice. The same approach applied on Hamlin juice from the next harvest year as well as on chilled stored NFC juice from Valencia oranges confirmed the results for another harvest year and another orange variety.

Identification and Quantitation of Four New 2-Alkylthiazolidine-4-carboxylic Acids Formed in Orange Juice by a Reaction of Saturated Aldehydes with Cysteine.

Despite several technological efforts to maximize the quality and shelf life of chilled stored not-from-concentrate orange juice, changes in the overall aroma profile might occur during storage. Besides the degradation of terpenoids, a loss of the aroma-active aldehydes, hexanal, octanal, nonanal, and decanal as well-as of 1-penten-3-one were recently confirmed as a major cause for the changes in the aroma profile of orange juice even during storage under aseptic conditions at 0 °C. To unravel the fate of the aroma-active aldehydes, model experiments were carried out considering the oxidation into the corresponding acids as well as a reaction with free amino acids present in orange juice. The oxidation into the acids could be confirmed by isotope labeling experiments; additionally, the reaction of the four aldehydes mentioned above with l-cysteine yielded four new compounds identified as 2-alkylsubstituted thiazolidine-4-carboxylic acids. Their quantitation in orange juice samples by newly developed stable isotope dilution assays revealed that these acids were already present in the fresh samples but were considerably increased after storage. Labeling experiments in orange juice administered with either labeled octanal or labeled cysteine confirmed that the reaction quickly occurs in the juice. The data contribute another puzzle piece to the loss of aroma-active aldehydes during orange juice storage, which may also be relevant in other foods.

New Degradation Pathways of the Key Aroma Compound 1-Penten-3-one during Storage of Not-from-Concentrate Orange Juice.

1-Penten-3-one with its fresh and pungent smell at a very low odor threshold of 0.94 µg/L water has been characterized as impact aroma compound in many foods, such as grapefruit, orange juice, black tea, olive oil, or tomatoes. While its importance to the fresh sensation of unstored not-from-concentrate (NFC) orange juice was recently confirmed by aroma recombinates, a total loss was determined already after 4 weeks in NFC orange juice stored at 0 °C. Until now, the degradation pathway of this compound has not been clarified. Systematic model studies resulted in the identification of 1-hydroxy-3-pentanone and 4-hydroxy-3,8-decanedione as degradation products as well as S-(3-oxopentyl)-l-cysteine in the presence of the amino acid. In orange juice samples, it was found that the elevated content of 1-hydroxy-3-pentanone indicates a thermal processing, while S-(3-oxopentyl)-l-cysteine showed a significant increase during cold storage. Additionally, both compounds were identified in other food samples, such as commercial orange juices, pickled olives and olive oil, fresh tomatoes and commercial tomato juice, and black tea.