A novel homozygous frameshift mutation in / 亚洲男科学杂志(英文版)

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

Abnormal fertilization in ICSI and its association with abnormal semen parameters: a retrospective observational study on 1855 cases / 亚洲男科学杂志(英文版)

Intracytoplasmic sperm injection (ICSI) efficiently addresses male factor infertility. However, the occurrence of abnormal fertilization, mainly characterized by abnormal pronuclei (PN) patterns, merits investigation. To investigate abnormal fertilization patterns following ICSI and identify their respective associations with abnormal parameters in semen analysis (SA), a retrospective observational study including 1855 cycles was performed. Male infertility diagnosis relied on the 2010 WHO criteria. The population was divided into groups based on their SA results. The presence of 2PNs and extrusion of the second polar body (PB) indicated normal fertilization. A Kruskal-Wallis test along with a Wilcoxon post hoc evaluation and Bonferroni correction was employed for comparison among the groups. For the pregnancy rate, logistic regression was employed. No correlation was established between the SA abnormalities and the 1PN or 3PN formation rates. The highest and lowest 0PN rates were reported for the oligoasthenoteratozoospermic and normal groups, respectively. The lowest cleavage formation rates were identified in the oligoasthenozoospermic and oligoasthenoteratozoospermic groups. The aforementioned groups along with the oligoteratozoospermic group similarly presented the lowest blastocyst formation rates. For the clinical pregnancy rate, no statistically significant difference was observed. In conclusion, the incidence of two or more abnormal SA parameters - with the common denominator being oligozoospermia - may jeopardize normal fertilization, cleavage, and blastocyst rates. Once the developmental milestone of achieving blastocyst stage status was achieved, only oligoasthenozoospermia and oligoasthenoteratozoospermia were associated with lower rates. Interestingly, following adjustment for the number of blastocysts, no statistically significant differences were observed.

The effects of oral antioxidants on the semen of men with idiopathic oligoasthenoteratozoospermia / 대한생식의학회지

It has been estimated that approximately 15% of reproductive-age couples suffer from infertility. Male factors contribute to almost half of infertility cases, and in many patients the underlying cause of oligoasthenoteratozoospermia is unknown. Accumulating evidence suggests that oxidative stress plays a role as a contributing factor to male infertility, and reactive oxygen species have been shown to impair sperm function and motility and to damage sperm membrane and DNA. Therefore, this review explored the evidence provided by studies published from 2002 to 2017 on the impact of oral antioxidants (vitamin C, vitamin E, L-carnitine, coenzyme Q10, zinc, selenium, and pentoxifylline) on seminal fluid parameters in men with idiopathic oligoasthenoteratozoospermia. Most of the studies were randomized controlled studies that investigated the effect of single or combined antioxidants and reported improvements in at least one semen parameter. The most noteworthy effect that was found was that the use of multiple antioxidants increased sperm motility and concentration. Nonetheless, there is a lack of agreement on the dose, the duration of treatment, and whether individual or combined oral antioxidants should be used. Therefore, the current review provides evidence supporting the use of oral antioxidants in the treatment of infertile men with idiopathic oligoasthenoteratozoospermia.

Thoughts and Approaches of Integrated Chinese and Western Medicine for the Treatment of Oligo-astheno-teratozoospermia / 中国结合医学杂志

Oligo-astheno-teratozoospermia (OAT) which perplexes doctors and patients due to its complicated etiology, atypical symptoms and poor clinical efficacy, is a general term for the three pathological states of abnormal semen. OAT is the main factor of male infertility. It is also a hot and difficult point in present studies. Empiric drug is the most popular treatment of this disease in the modern medicine. Chinese medicine (CM) is one of the main methods for the treatment of this disease, and it has certain clinical effect. The author believes that the use of modern medical technology to make the diagnosis as clear as possible is the key to treat OAT. The combination of syndrome and disease differentiation is the main mode in the treatment of OAT. Microscopic syndrome differentiation and macroscopic evidence embodies the basic principle of "Si Wai Chuai Nei" and broadens the perspective of CM syndrome differentiation. Classification and treatment are basic methods for the treatment of OAT. The treatment should not be limited to the Shen (Kidney), instead it should focus on the whole body condition. At different stages, the treatment should also pay attention to strengthening the Pi (Spleen), nourishing the Gan (Liver) and promoting blood circulation. Complementing Chinese and Western medicine, and highlighting the characteristics and advantages of CM treatment, have a great guiding value for the treatment of OAT.

Comparison between intracytoplasmic sperm injection and intracytoplasmic morphologically selected sperm injection in oligo-astheno-teratozoospermia patients / 대한생식의학회지

OBJECTIVE: The aim of this study was to evaluate the efficiency of the intracytoplasmic morphologically selected sperm injection (IMSI) technique compared with conventional ICSI and previous ICSI attempts in oligo-astheno-teratozoospermia (OAT) patients. METHODS: The sperms were selected under high magnification (6,600x) and used to induce fertilization in previous ICSI patients by IMSI. These results were compared with previous conventional ICSI cycles in patients with OAT infertility. RESULTS: These results demonstrated no significant difference in the fertilization rate between IMSI and previous ICSI cycles (67.7% vs. 65.0%). However, the pregnancy and implantation rates with IMSI were significantly higher than those of the ICSI cycles (33.3% vs. 12.5% and 14.6% vs. 5.4%, respectively; p<0.05). The miscarriage rate among pregnant patients (18.2% vs. 37.5%) showed no statistically significant difference between groups. CONCLUSION: Compared to conventional ICSI, this study found that IMSI increased the IVF-ET success rates in patients with OAT.

A case of oligoasthenoteratozoospermia with AZFc deletion and persistent oxidative stress.

Y-chromosomal microdeletions are associated with severe oligozoospermia or azoospermia. AZFc microdeletions have been always associated with severe oligozoospermia or azoospermia with a rare occurrence in individuals with other infertility phenotypes. We report here a rare case of an infertile man carrying AZFc deletion, whose semen picture is oligoasthenoteratozoospermia complexed with seminal oxidative stress. Anti-oxidant therapy could make no change in either oxidative stress biomarker levels of semen, seminal parameters or serum hormone levels. Therefore, oligoasthenoteratozoospermia in the present case correlates with AZFc deletion, and high content of abnormal sperm eventually might be responsible for persistently elevated reactive oxygen species levels. Understanding the function of genes in AZFc region could help decipher the exact cause of the phenotype in such cases.

Spermatogenic alterations in men with high testiculo epididymal temperatures.

Sperms are produced by a highly complex and poorly understood differentiation process known as spermatogenesis. Occupational exposure to high temperatures adversely affect testicular function causing partial or complete spermatogenic arrest. Dyers, cooks, blast furnace workers and men with varicocele are known to develop testicular hyperthermia, which leads to oligoasthenoteratozoospermia (OAT) and azoospermia. Semen analysis of 125 infertile men (and 25 fertile controls following the WHO guidelines, 1999 showed azoospermia in 109 men and oligozoospermia in 16 men. Twenty azoospermic and 14 oligozoospermic men had high testiculoepididymal temperatures either due to occupational exposure to high temperature or varicocele. All the 14 oligozoospermic men showed a very high percentage of sperms with abnormal morphology, impaired motility and they were subclassified as OAT group. Observations made in this study reiterates that high intratesticular temperature causes partial or complete spermatogenic arrest and may lead to increased production of morphologically abnormal sperms with impaired motility. This inverse relationship of sperm function with elevated temperature has implications in clinical medicine both in understanding pathological states and for therapeutic measures.

Intracyplasmic Sperm Injection in Patients with Past History of Failed or Poor Fertilization in Previous IVF - ET Cycles : Comparison with Patients with Severe Male Factor / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine whether intracytoplasmic sperm injection(ICSI) could overcome the defects of oocytes in IVF-ET patients with previous fertilization failure by conventional fertilization technique. Design: Retrospective study Materials and METHODS: A total of 119 ICSI cycles in 57 IVF-ET patients performed from May, 1995 to December, 1997 was enrolled. Subjects were divided into two groups: FR group included 66 ICSI cycles in 35 patients with normal sperm who underwent ICSI due to past history of failed or poor fertilization in the previous IVF-ET cycles, and OAT group included 53 ICSI cycles in 22 patients with severe oligoasthenoterato- zoospermia(OAT) which was defined as sperm concentration < 20 million/ml, mo#dlity < 30% and normal morphology < 4% by strict morphologic criteria. The outcomes of ICSI were analyzed and compared in both groups. RESULTS: The age of female patients, basal serum FSH level, and the numbers of oocytes retrieved and metaphase II oocytes were all comparable in both groups. The fertilization rate after ICSI was similar in both groups(68.7+/-25.3% vs. 67.7+/-24.5%), as were the cleavage rate of normally fertilized oocytes(93.1+/-21.4% vs. 89.3+/-21.6%), the number of embryos transferred(4,00+/-1.98 vs. 4.64+/-2.10), and cumulative embryo score(CES) indicating the quality of embryos(47.3+/-33.2 vs. 54.1+/-33.2). The implantation rate(4.3+/-10.5% vs. 3.8+/-11.0%) and the clinical pregnancy rate per cycle(15.2% vs. 13.2%) were also comparable in both groups. CONCLUSIONS: Although it has been shown that there is a higher risk of chromosomal abnormalities in oocytes from IVF-ET patients with pevious failed or poor fertilization, higher implantation and clinical pregnancy rates wer#e not observed in patients with OAT following ICSL Therefore, the functional defect of sperm such as loss of capacitation, defect of aaasome reaction, and abnormality of nucleus decondensation should be also considered in patients with previous failed or poor fertilization.