Shear wave elastography to assess stiffness of the human ovary and other reproductive tissues across the reproductive lifespan in health and disease†.

The ovary is one of the first organs to show overt signs of aging in the human body, and ovarian aging is associated with a loss of gamete quality and quantity. The age-dependent decline in ovarian function contributes to infertility and an altered endocrine milieu, which has ramifications for overall health. The aging ovarian microenvironment becomes fibro-inflammatory and stiff with age, and this has implications for ovarian physiology and pathology, including follicle growth, gamete quality, ovulation dynamics, and ovarian cancer. Thus, developing a non-invasive tool to measure and monitor the stiffness of the human ovary would represent a major advance for female reproductive health and longevity. Shear wave elastography is a quantitative ultrasound imaging method for evaluation of soft tissue stiffness. Shear wave elastography has been used clinically in assessment of liver fibrosis and characterization of tendinopathies and various neoplasms in thyroid, breast, prostate, and lymph nodes as a non-invasive diagnostic and prognostic tool. In this study, we review the underlying principles of shear wave elastography and its current clinical uses outside the reproductive tract as well as its successful application of shear wave elastography to reproductive tissues, including the uterus and cervix. We also describe an emerging use of this technology in evaluation of human ovarian stiffness via transvaginal ultrasound. Establishing ovarian stiffness as a clinical biomarker of ovarian aging may have implications for predicting the ovarian reserve and outcomes of Assisted Reproductive Technologies as well as for the assessment of the efficacy of emerging therapeutics to extend reproductive longevity. This parameter may also have broad relevance in other conditions where ovarian stiffness and fibrosis may be implicated, such as polycystic ovarian syndrome, late off target effects of chemotherapy and radiation, premature ovarian insufficiency, conditions of differences of sexual development, and ovarian cancer. Summary sentence:  Shear Wave Elastography is a non-invasive technique to study human tissue stiffness, and here we review its clinical applications and implications for reproductive health and disease.

Differential Association of FTO Gene variants and Haplotypes with the Susceptibility to Polycystic Ovary Syndrome According To Obesity in Women with PCOS.

We explored the relation between FTO single gene variants (rs1861868, rs9939973, rs1421085, rs1121980, rs17817449, rs8050136, rs9939609, rs9930506, and rs8044769) and polycystic ovary syndrome (PCOS), in particular, according to the obesity status. This retrospective population-based case-control study involved women with PCOS (583) and 713 eumenorrheic control women; genotyping was done by real-time PCR. Significantly higher minor allele frequency (MAF) of rs9939973, rs17817449, rs9939609, and rs9930506 and lower MAF of rs1121980 were seen in PCOS cases. Lower risk of PCOS was associated with rs1121980 and rs8050136 heterozygous and minor allele-homozygous genotypes, while an elevated risk of PCOS was seen with minor allele-homozygous rs9939973, rs17817449, and r9939609 heterozygous and genotypes and minor allele-homozygous rs9930506 and rs8044769 genotype. While none of the tested FTO SNPs variants was associated with PCOS in normal body weight/lean subjects, rs9939973, rs9939609, and rs9930506 were negatively associated with PCOS in overweight subjects. In comparison, rs1861868 was negatively, while rs8044769 was positively associated with PCOS in obese subjects. Haplotype analysis identified haplotypes GACCTCTAT, AACCTCTAT, AACCTATAT and AGTTGCAGC, and GACCTCTAC to be positively associated with PCOS, while haplotypes GGTTGAAGC, GACCTATAT, GGTTGCAGC, and GATCTATAT were negatively associated with PCOS. Apart from GGTTGAAGC, these haplotypes remained associated with altered risk of PCOS after adjusting for covariates. In addition to rs17817449, rs9939609, rs9930506, and rs1121980, this study is the first to demonstrate association of rs9939973 and rs8044769 with altered risk of PCOS and the first to confirm the BMI dependency on the association of FTO variants with PCOS. This underscores the role of FTO gene variants as predisposing factors of PCOS.

Automation in ART: Paving the Way for the Future of Infertility Treatment.

In vitro fertilisation (IVF) is estimated to account for the birth of more than nine million babies worldwide, perhaps making it one of the most intriguing as well as commoditised and industrialised modern medical interventions. Nevertheless, most IVF procedures are currently limited by accessibility, affordability and most importantly multistep, labour-intensive, technically challenging processes undertaken by skilled professionals. Therefore, in order to sustain the exponential demand for IVF on one hand, and streamline existing processes on the other, innovation is essential. This may not only effectively manage clinical time but also reduce cost, thereby increasing accessibility, affordability and efficiency. Recent years have seen a diverse range of technologies, some integrated with artificial intelligence, throughout the IVF pathway, which promise personalisation and, at least, partial automation in the not-so-distant future. This review aims to summarise the rapidly evolving state of these innovations in automation, with or without the integration of artificial intelligence, encompassing the patient treatment pathway, gamete/embryo selection, endometrial evaluation and cryopreservation of gametes/embryos. Additionally, it shall highlight the resulting prospective change in the role of IVF professionals and challenges of implementation of some of these technologies, thereby aiming to motivate continued research in this field.