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Objective: Ovarian tissue vitrification is widely utilized for fertility preservation in prepubertal and adolescent female patients with cancer. The current literature includes reports of successful pregnancy and live birth following autografting. However, the effects of the vitrification process on cumulus-mural granulosa cells (C-mGCs)-somatic cells in ovarian tissue crucial for oocyte maturation and early embryonic development-remain unclear. This study was conducted to explore the impact of vitrification on the cellular function of C-mGCs by quantifying the expression of growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), connexin 37, survivin, and caspase 3., Methods: Mature and immature C-mGCs were obtained from 38 women with polycystic ovary syndrome who participated in an in vitro fertilization program. The C-mGCs were then divided into two groups: fresh and vitrified. The expression levels of target genes were assessed using real-time quantitative polymerase chain reaction., Results: After vitrification, GDF-9 expression was significantly decreased among both mature and immature C-mGCs, with 0.2- and 0.1-fold changes, respectively (p<0.01). Similarly, FSHR expression in the mature and immature groups was reduced by 0.1- and 0.02-fold, respectively, following vitrification (p<0.01). The expression levels of the other genes, including BMP-15, LHR, connexin 37, survivin, and caspase 3, remained similar across the examined groups (p>0.05)., Conclusion: Vitrification may compromise oocyte maturation through reduced GDF-9 and FSHR expression in C-mGCs after warming.

Objective: The presence of embryonic cell-free DNA (cfDNA) in spent embryo culture media (SECM) may offer valuable advantages for non-invasive testing of embryo ploidy or genetic characteristics compared to trophectoderm (TE) biopsy. This study aimed to assess the diagnostic potential of SECM cfDNA as a non-invasive sample for chromosomal copy number testing in blastocysts within the clinical setting of in-vitro fertilization., Method: This prospective observational study collected 28 SECM cfDNA samples matched with TE biopsy samples from 21 infertile couples who underwent IVF-PGT-A cycles. SECM samples were obtained from blastocysts that were cultured for approximately 5/6 days in an uninterrupted time-lapse incubator. Both sets of samples were collected during the biopsy procedure. The Variseq Illumina platform was utilized for ploidy measurement. The study evaluated the informativity and interpretability of SECM cfDNA, concordance of general ploidy status, and sex chromosome agreement between the two sample types., Results: SECM cfDNA had a high informativity rate (100 %) after double amplification procedure, with a result interpretability of 93 %. Two out of the 28 SECM cfDNA samples were uninterpretable and regarded as overall noise samples. The diagnostic potential of SECM cfDNA, when compared to TE biopsy the standard reference, was relatively low at 50 %. Maternal DNA contamination remains the major obstacle that hinders the widespread clinical adoption of SECM cfDNA in the routine practice of pre-implantation genetic testing for aneuploidy within IVF settings., Conclusion: A significant modification must be implemented in the IVF laboratory to minimize DNA contamination and this necessitates suggesting adjustments to oocyte denudation, embryo culture media preparation, and sample collection procedures., Competing Interests: Conflict of interest statement The authors declared no competing interests to disclose, (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: This research was conducted to assess access to assisted reproductive technologies (ART) and the current status of the in vitro fertilization (IVF) program that have been implemented in Indonesia over the last 10 years., Methods: We established a retrospective cohort study and descriptive analysis of the current state of access to infertility care in Indonesia. The data were collected from all IVF centers, clinics, and hospitals in Indonesia from 2011 to 2020, including the number of IVF clinics, total ART cycles, retrieved fresh and frozen embryos, average age of IVF patients, IVF pregnancy rate, and causes of infertility., Results: The number of reported fertility clinics in Indonesia has increased from 14 clinics in 2011 to 41 clinics by 2020. As many as 69 569 ART cycles were conducted over the past 10 years, of which 51 892 cycles used fresh embryos and 17 677 cycles used frozen embryos. The leading cause of consecutive infertility diagnosis was male infertility. Nearly half of the women who underwent IVF procedures (48.9%) were under 35 years old. The pregnancy rate outcome of women who underwent IVF ranged from 24.6% to 37.3%., Conclusion: Developments in ART in Indonesia have led to improvements in the ART cycles performed throughout the 10 year period. The identification of key areas that require improvement can provide an opportunity to enhance access to infertility care., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Several approaches have been proposed to optimize the construction of an artificial intelligence-based model for assessing ploidy status. These encompass the investigation of algorithms, refining image segmentation techniques, and discerning essential patterns throughout embryonic development. The purpose of the current study was to evaluate the effectiveness of using U-NET architecture for embryo segmentation and time-lapse embryo image sequence extraction, three and ten hr before biopsy to improve model accuracy for prediction of embryonic ploidy status., Methods: A total of 1.020 time-lapse videos of blastocysts with known ploidy status were used to construct a convolutional neural network (CNN)-based model for ploidy detection. Sequential images of each blastocyst were extracted from the time-lapse videos over a period of three and ten hr prior to the biopsy, generating 31.642 and 99.324 blastocyst images, respectively. U-NET architecture was applied for blastocyst image segmentation before its implementation in CNN-based model development., Results: The accuracy of ploidy prediction model without applying the U-NET segmented sequential embryo images was 0.59 and 0.63 over a period of three and ten hr before biopsy, respectively. Improved model accuracy of 0.61 and 0.66 was achieved, respectively with the implementation of U-NET architecture for embryo segmentation on the current model. Extracting blastocyst images over a 10 hr period yields higher accuracy compared to a three- hr extraction period prior to biopsy., Conclusion: Combined implementation of U-NET architecture for blastocyst image segmentation and the sequential compilation of ten hr of time-lapse blastocyst images could yield a CNN-based model with improved accuracy in predicting ploidy status., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright© 2024, Journal of Reproduction & Infertility.)

The presence of cell-free DNA in spent embryo culture media (SECM) has unveiled its possible utilization for embryonic ploidy determination, opening new frontiers for the development of a non-invasive pre-implantation genetic screening technique. While a growing number of studies have shown a high concordance between genetic screening using cell-free DNA (cfDNA) and trophectoderm (TE), the mechanism pertaining to the release of cfDNA in SECM is largely unknown. This review aims to evaluate research evidence on the origin and possible mechanisms for the liberations of embryonic DNA in SECM, including findings on the self-correction abilities of embryos which might contribute to the presence of cfDNA. Several databases including EMBASE, PUBMED, and SCOPUS were used to retrieve original articles, reviews, and opinion papers. The keywords used for the search were related to the origins and release mechanism of cfDNA. cfDNA in SECM originates from embryonic cells and, at some levels, non-embryonic cells such as maternal DNA and exogenous foreign DNA. The apoptotic pathway has been demonstrated to eliminate aneuploid cells in developing mosaic embryos which might culminate to the release of cfDNA in SECM. Nonetheless, there is a recognized need for exploring other pathways such as cross-talk molecules called extracellular vesicles (EVs) made of small, round bi-layer membranes. During in vitro development, embryos physiologically and actively expel EVs containing not only protein and microRNA but also embryonic DNA, hence, potentially releasing cfDNA of embryonic origin into SECM through EVs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Preimplantation genetic testing for aneuploidy has been proven to be effective in determining the embryo's chromosomal or ploidy status. The test requires a biopsy of embryonic cells on day 3, 5, or 6 from which complete information on the chromosomes would be obtained. The main drawbacks of preimplantation genetic testing for aneuploidy include its relatively invasive approach and the lack of research studies on the long-term effects of preimplantation genetic testing for aneuploidy., Objective: Computer-assisted predictive modeling through machine learning and deep learning algorithms has been proposed to minimize the use of invasive preimplantation genetic testing for aneuploidy. The capability to predict morphologic characteristics of embryo ploidy status creates a meaningful support system for decision-making before further treatment., Study Design: Image processing is a component in developing a predictive model specialized in image classification through which a model is able to differentiate images based on unique features. Image processing is obtained through image augmentation to capture segmented embryos and perform feature extraction. Furthermore, multiple machine learning and deep learning algorithms were used to create prediction-based modeling, and all of the prediction models undergo similar model performance assessments to determine the best model prediction algorithm., Results: An efficient artificial intelligence model that can predict embryo ploidy status was developed using image processing through a histogram of oriented gradient and then followed by principal component analysis. The gradient boosting algorithm showed an advantage against other algorithms and yielded an accuracy of 0.74, an aneuploid precision of 0.83, and an aneuploid predictive value (recall) of 0.84., Conclusion: This research study proved that machine-assisted technology perceives the embryo differently than human observation and determined that further research on in vitro fertilization is needed. The study finding serves as a basis for developing a better computer-assisted prediction model., (© 2023 The Authors.)

Fertility preservation through gamete vitrification has become one of the critical strategies to secure a childbearing potential in patients who are diagnosed with cancer or risks of infertility. Preserving the gametes would prevent the deleterious effects of cancer drugs or radiotherapy exposure on the quality of the gametes. Furthermore, in vitro fertilisation of vitrified mature human oocytes has lately demonstrated promising results that are reflected in the increased survival rate of thawed oocytes and the resultant clinical pregnancy rate. However, limitations in the cryopreservation of mature oocytes of cancer patients persist. Ovarian stimulation protocols which comprise administering gonadotrophin-releasing hormones could aggravate cancer or delay essential cancer therapy. Considering such circumstances, vitrification of immature oocytes would become a rational option. While the vitrification procedure of mature oocytes has been established, the vitrification of immature oocytes remains controversial due to a low post-thaw in vitro maturation and fertilisation rate. Apparent cryoinjuries to the immature oocytes post thawing or warming have been observed in both human and animal model oocytes. An alternative strategy was therefore proposed to improve the effectiveness of utilising immature oocytes for fertility preservation by conducting the in vitro oocyte maturation process first before vitrification. This method has prevailed, especially in oncofertility patients. Although the success rate of the clinical outcomes remains low, this approach, in conjugation with proper counselling, might provide oncofertility patients with an opportunity to preserve their reproductive potential., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Human Reproductive Sciences.)

Oocyte developmental competence is one of the determining factors that influence the outcomes of an IVF cycle regarding the ability of a female gamete to reach maturation, be fertilized, and uphold an embryonic development up until the blastocyst stage. The current approach of assessing the competency of an oocyte is confined to an ambiguous and subjective oocyte morphological evaluation. Over the years, a myriad of biomarkers in the cumulus-oocyte-complex has been identified that could potentially function as molecular predictors for IVF program prognosis. This review aims to describe the predictive significance of several cumulus-oocyte complex (COC) biomarkers in evaluating oocyte developmental competence. A total of eight acclaimed cumulus biomarkers are examined in the study. RT-PCR and microarray analysis were extensively used to assess the significance of these biomarkers in foreseeing oocyte developmental competence. Notably, these biomarkers regulate vital processes associated with oocyte maturation and were found to be differentially expressed in COC encapsulating oocytes of different maturity. The biomarkers were reviewed according to the respective oocyte maturation events namely: nuclear maturation, apoptosis, and extracellular matrix remodeling, and steroid metabolism. Although substantial in vitro evidence was presented to justify the potential use of cumulus biomarkers in predicting oocyte competency and IVF outcomes, the feasibility of assessing these biomarkers as an add-on prognostic procedure in IVF is still restricted due to study challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sirait, Wiweko, Jusuf, Iftitah and Muharam.)