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Purpose: Genetic factors associated with the risk of polycystic ovary syndrome (PCOS) remain largely unknown. Here, we conducted an optimal sequence kernel association test (SKAT‐O), an exome‐based rare variant association study, to clarify whether rare variants in specific genes contribute to the development of PCOS. Methods: SKAT‐O was performed using exome data of 44 Japanese patients with PCOS and 301 control women. We analyzed frequencies of rare probably damaging variants in the genome. Results: Rare variants of GSTO2 were more commonly identified in the patient group than in the control group (6/44 vs. 1/301; Bonferroni‐corrected p‐value, 0.028), while the frequencies of variants in other genes were comparable between the two groups. The identified GSTO2 variants were predicted to affect the function, structure, stability, hydrophobicity, and/or the formation of intrinsically disordered regions of the protein. GSTO2 encodes a glutathione transferase that mediates the oxidative stress response and arsenic metabolism. Previously, common variants in GSTO2 and its paralog GSTO1 were associated with the risk of PCOS. Conclusions: The results indicate that there are no genes whose rare variants account for a large fraction of the etiology of PCOS, although rare damaging variants in GSTO2 may constitute a risk factor in some cases. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the clinical results of Japanese men with Y chromosome microdeletions. Methods: This study retrospectively examined 2163 azoospermic or severe oligozoospermic patients. We investigated the frequency of azoospermia factor (AZF) deletions and sperm retrieval rate (SRR) by microTESE in patients with these deletions, then analyzed the ICSI outcomes. Results: Azoospermia factor deletions were found in 201 patients. SRR was significantly higher than that of the control group (74.0% vs 20.4%, P <.001). Thirty‐three couples underwent ICSI using testicular spermatozoa retrieved by microTESE, and eight couples underwent ICSI using ejaculatory spermatozoa. The fertilization rate and clinical pregnancy rate per embryo transfer cycle were significantly higher in the ejaculatory group than that of the testicular group (66.4% vs 43.7%, P <.001, 53.3% vs 24.7%, P =.03, respectively). When compared with the control group, the fertilization rate was significantly lower in the testicular group with AZFc microdeletions (43.7% vs 53.6%, P <.001). Conclusions: Our study highlights that although microTESE in azoospermic men with AZFc microdeletions led to a higher SRR, ICSI outcomes of these men were worse than that of men without AZF deletions, even if testicular spermatozoa were retrieved. [ABSTRACT FROM AUTHOR]

Purpose: In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations. Methods: To elucidate the clinical usefulness of in vitro‐fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen‐thawed 1PN‐ and 0PN‐derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan. Results: The rates of pregnancy and live birth for 1PN‐derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 0PN‐derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN‐derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 1PN‐derived blastocysts were significantly lower (4.0% for both) than those for 2PN‐ and 0PN‐derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN‐ or 1PN‐derived blastocysts. Conclusions: Both 1PN‐ and 0PN‐derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN‐derived blastocysts, especially if they are obtained by ICSI. [ABSTRACT FROM AUTHOR]

Purpose: As age increases, oxidative stress increases, sperm motility decreases, and DNA fragmentation increases. To date, reports of age-related effects on semen have focused on reactive oxygen species (ROS) or total antioxidant capacity (TAC) as indicators of oxidative stress. However, assessments of ROS and TAC must be considered within a more comprehensive context in order to correctly evaluate oxidative stress and interpret findings. In this regard, the purpose of this study was to investigate the relationship between the static oxidation reduction potential (sORP) and paternal age with the goal of using the sORP as an indicator of semen oxidative stress., Materials and Methods: Semen samples from 173 men were analyzed for the following parameters: volume, motility, and beat cross frequency (BCF). The sORP was measured by using the MiOXSYS™ system. The correlation between semen parameters and the sORP level was analyzed as a function of age. The rate of sORP positivity was compared between men <34 and ≥34 years of age, with a positive sORP defined as a level ≥1.38., Results: Volume, motility, and BCF were negatively correlated with age (p<0.001). The semen sORP level was positively correlated with age (p<0.05). The rate of sORP positivity was significantly increased in men ≥34 years of age compared with that in men <34 years of age (33% compared with 12%, respectively; p<0.01)., Conclusions: The sORP may play a role in age-related decreases in semen parameters (volume, motility, and BCF). The rate of sORP positivity increased significantly after 34 years of age., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

The epigenetic status of the genome changes dynamically from fertilization to implantation. In addition, the physiological environment during the process of gametogenesis, including parental age, may affect the epigenome of the embryo after fertilization. It is important to clarify the influence of parental age on gene expression in the embryo in terms of transgenerational epigenetics to improve the techniques currently used in assisted reproductive medicine. Here, we performed single-embryo RNA-seq analysis on human blastocysts fertilized by intracytoplasmic sperm injection, including from relatively elderly mothers, to elucidate the effects of parental age on the embryonic gene expression profile. We identified a number of genes in which the expression levels were decreased with increasing maternal age. Among these genes, several are considered to be important for meiotic chromosomal segregation, such as PTTG1, AURKC, SMC1B and MEIKIN. Furthermore, the expression levels of certain genes critical for autophagy and embryonic growth, specifically GABARAPL1 and GABARAPL3, were negatively correlated with advanced paternal age. In addition, levels of transcripts derived from major satellite repeats also decreased as the maternal age increased. These results suggest that epigenetic modifications of the oocyte genome may change with parental age and be transmitted to the next generation.