To dissect the genetic alteration in two sisters with premature ovarian insufficiency (POI) from a consanguineous family. Whole-exome sequencing technology was used in the POI proband, bioinformatics analysis was carried out to identify the potential genetic cause in this pedigree. Sanger sequencing analyses were performed to validate the segregation of the variant within the pedigree. In silico analysis was also used to predict the effect and pathogenicity of the variant. Whole-exome sequencing analysis identified novel and rare homozygous mutation associated with POI, namely mutation in FIGLA (c.2 T > C, start codon shift). This homozygous mutation was also harbored by the proband’s sister with POI and was segregated within the consanguineous pedigree. The mutation in the start codon of the FIGLA gene alters the open reading frame, leading to a FIGLA knock-out like phenotype. Biallelic mutations in FIGLA may be the cause of POI. This study will aid researchers and clinicians in genetic counseling of POI and provides new insights into understanding the mode of genetic inheritance of FIGLA mutations in POI pathology.

Melatonin (MT) can improve the effect of cryopreservation on oocytes by suppressing oxidative stress and maintaining the permeability of the oolemma. In this study, MT was firstly applied to human oocytes’ cryopreservation to explore the effect of prolonged cryopreservation on developmental competence and its role. Collected in vitro-matured human oocytes were cryopreserved in MT-containing or MT-free medium for 0 and 6 months; after warming, viable oocytes were assessed for developmental viability, intracellular protein expression, mitochondrial function, and oxidation-antioxidant system. Meanwhile, fresh oocytes were set as the control. The results showed that with the extension of cryopreservation time, the developmental competence of oocytes gradually declined, accompanied by the down-regulation of most mitochondrial function-related proteins, the reduction in ATP and GSH production, the increase in ROS accumulation, and the aggravation of the imbalance of ROS/GSH in oocytes. However, the participation of MT seemed to effectively mitigate these negative effects. Therefore, we speculate that melatonin may maintain normal ATP production and ROS/GSH balance in cryopreserved oocytes by protecting mitochondrial function and inhibiting oxidative damage, thereby effectively maintaining the developmental competence of human oocytes in prolonged cryopreservation.

Lin Li, Linfan Mao, Zhiguo Zhang, Yiying Yu, Miaohui Ding, Yongyan Zhi, Yunxia Cao, Beili Chen, Jie Na; Mutations in TUBA4A lead to human zygotic arrest and ear

The etiology of Müllerian duct anomalies (MDAs) is poorly understood at present. The HOXA11 gene is crucial for the development of the Müllerian duct. The objective of this study is to report a unique case of MDAs with a novel mutation in HOXA11. We identified a potential disease-causing mutation (p. E255K) in a patient with a septate uterus. The mutation was not detected in 169 control subjects or listed in any databases of variations. Bioinformatic predictions and functional studies showed that the mutation reduces the DNA binding affinity and disrupts transactivation ability of HOXA11. In conclusion, this is the first report to describe a HOXA11 mutation in Chinese women with MDAs. The results demonstrated that mutation in HOXA11 can contribute to the etiology of MDAs, especially the septate uterus, but might not be a common cause.

Zona pellucida (ZP) abnormalities are the cause of low fertility or infertility, agar-like ZP is more common in abnormal ZP. The purpose of this exploration is to systematically analyze the fertilization competence of agar-like ZP oocytes, the development characteristics of subsequent embryos as well as the results of embryo transfer, aiming to explore effective clinical treatment strategies. A total of 58 patients with agar-like ZP were set as the case group and the control group involved 3866 patients, in which the patients’ oocytes presented normal ZP. BMI, basal hormone levels, and hormone levels were similar in both groups. The case patients suffered significantly longer infertility years than control (p<0.05), and most patients were diagnosed with pelvic inflammatory diseases. A distinct difference was observed in the structure of oocyte corona cumulus complexes between the two groups. The embryo development parameters, which include the rates of cleavage, high-quality embryo, blastocyst, and high-quality blastocyst in the case group were greatly lower than that in the control group (p<0.05). The rates of cumulative clinical pregnancy and live birth were comparable between the two groups. In the subsequent follow-up, thirty-four of the 58 patients receiving intracytoplasmic single sperm injection (ICSI) or early rescue ICSI (R-ICSI) treatment successfully gave birth to babies, and all of the newborns were with no neonatal defects. In addition, the fertilization rate of the R-ICSI group was significantly lower than that of the ICSI group (p<0.05). The occurrence of agar-like ZP impairs the development competence of human oocytes, however, the human oocytes with agar-like ZP can develop into healthy offspring, and an ICSI regimen is the optimal treatment strategy for them.

Summary: This study aimed to analyze the clinical effects of microdissection testicular sperm extraction (micro-TESE) surgery combined with an intracytoplasmic sperm injection (ICSI) regimen in the treatment of non-obstructive azoospermia (NOA) patients with different etiologies. In total, 128 NOA patients participated in this study, in which they received infertility treatment by micro-TESE surgery combined with an ICSI regimen, and all patients were divided into three groups [the Klinefelter syndrome (KS), the idiopathic and the secondary NOA groups]. In addition, the sperm retrieval rate (SRR), fertilization rate, embryo development status and clinical treatment effects were analyzed. Among the 128 NOA patients, the SRR of KS NOA patients was 48.65%, those of idiopathic and the secondary patients were 33.82% and 73.91%, respectively. Regardless of etiologies, there was no correlation with age, hormone value or testicular volume. Further analysis showed that the SRR of the KS group was positively related with testosterone (T) values, and the SRR of the secondary group had a positive relationship with follicle-stimulating hormone or luteinizing hormone values. In the subsequent clinical treatment, the retrieved sperm was subjected to ICSI and achieved good treatment effects, especially in the secondary group, and the implantation rate (55.56%) and clinical pregnancy rate (68.42%) were both higher than those of the idiopathic group (28.75% and 40.00%) and KS group (22.05% and 30.77%). Micro-TESE surgery combined with ICSI insemination is the most effective treatment regimen for NOA patients. The SRR of NOA patients with different etiologies are related to certain specific factors, and micro-TESE surgery seems to be the ideal and only way to have biological children.