Whole exome sequencing and trio analysis to broaden the variant spectrum of genes in idiopathic hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

Sperm DNA fragmentation in Chinese couples with unexplained recurrent pregnancy loss / 亚洲男科学杂志(英文版)

We aimed to study the association between sperm DNA fragmentation and recurrent pregnancy loss (RPL) in the Chinese population via a retrospective observational study of Chinese couples who had experienced RPL between May 2013 and August 2018. The study population included 461 men from couples with RPL and 411 men from a control group (couples with clinical pregnancy via in vitro fertilization owing to female causes). Routine semen analysis, sperm chromatin analysis, and microscopic (high-power) morphological analysis were performed using semen samples. Semen samples were assessed for volume, sperm count, and motility. The sperm DNA fragmentation index (DFI) was calculated, and the median DFI was obtained. Men were categorized as having normal (37.8%; DFI ≤ 15.0%), moderate (33.6%; 15.0% < DFI < 30.0%), or severe (28.6%; DFI ≥ 30.0%) DNA fragmentation levels. The percentage of men with severe DNA fragmentation was significantly higher in the RPL (42.3%) group than that in the control group (13.1%), whereas the percentage of men with normal levels of DNA fragmentation was significantly lower in the RPL group (22.8%) than that in the control group (54.7%). Subsequent analysis also demonstrated that the sperm DNA fragmentation rate had a moderate reverse correlation with the sperm progressive motility rate (r = -0.47, P < 0.001) and the total motile sperm count (r = -0.31, P < 0.001). We found a positive correlation between RPL and sperm DNA fragmentation. The results suggest that increased sperm DNA damage is associated with RPL.

Y chromosome microdeletions: detection in 1 052 infertile men and analysis of 14 of their families / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of father-to-son vertical transmission of Y chromosome microdeletions</p><p><b>METHODS</b>We detected the Y by detection of Y chromosome microdeletions in infertile men and analysis of some of their families. chromosome azoospermia factor (AZF) microdeletions in the peripheral blood of 1 052 infertile males, investigated the paternal relatives of 12 cases of AZFc, 1 case of AZFb and 1 case of AZFb + c microdeletions, and drew the family tree diagrams of the infertile paternal relatives according to the findings.</p><p><b>RESULTS</b>Among the 1 052 infertile patients, 89 (9.73%) were found with Y chromosomal microdeletions, including 56 with AZFc, 6 with AZFa, 5 with AZFb, 14 with AZFb + c, and 8 with AZFa + b + c deletion. The investigation of the 14 patients'families revealed 1 case of AZFb and 1 case of AZFb + c deletion de novo. Among the 12 cases of AZFc deletion, vertical heredity was found in 5 patients with severe oligozoospermia, but not in the other 7 with azoospermia.</p><p><b>CONCLUSION</b>AZFe deletion may be vertically inherited from the father in severe oligozoospermia patients, and it is different from the paternal phenotype, while in azoospermia patients, AZF deletion, whatever type it may be, is less likely to be associated with vertical paternal heredity.</p>

Immediate loading of implants in fully edentulous jaws: two cases report / 华西口腔医学杂志

Thirty-six implants were placed into 2 patients with fully edentulous jaws. Provisional prosthesis were placed into 34 of 36 implants which implant stability quotient (ISQ) was larger than 60 at the time of fixture placement. After 3 months, osseointegration of implants completed and permanence reparations were made. None implant lost among 18 months to 26 months since the immediate restoration was loaded. The average accumulate bone loss was 0.41 mm.

Immediate implant-support and overdenture retained by conical crowns: three cases report / 华西口腔医学杂志

Completed denture or immediate completed dentures were manufactured before operation to three patients with edentulous mandible and maxillary or severe chronic periodontitis. The remnant teeth of patients were extracted. Four Ankylos implants were implanted in mandible, and six implants were implanted in maxillary. SynCone conical bases were placed into implants, prefabricated conical crowns were inserted into conical bases, and temporary dentures were completed. After 3-12 months, temporary dentures were replaced by overdenture with casting frame. Except that one implant had been lost and was replaced by a new implant after 1 month of treatment, the rest implants had no obvious frontal resorption in 12-24 months of follow-up.

Genetic risks of intracytoplasmic sperm injection for male infertility / 中华男科学杂志

Recently, intracytoplasmic sperm injection (ICSI) has been extremely successful in the treatment of male infertility. However, the consequent transmission of sperm cytogenetic defects and genetic defects to the offspring has aroused considerable concern. Among infertile men, those with severe spermatogenic defects, including oligozoospermia and azoospermia, are mostly the subjects for ICSI. Therefore it is very important to obtain cytogenetic and chromosomal information on these infertile patients and prevent the inheritance of these genetic defects. This review offers an analysis on the genetic defects among infertile men.

Expression of OCTN2 mRNA in the human epididymis and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of L-Carnitine transport and the expression of OCTN2 mRNA in the human epididymis so as to provide a theoretical basis for male contraception.</p><p><b>METHODS</b>We collected specimens from human epididymides and determined the expressions of OCTN2 mRNA in the caput, corpus and cauda of the epididymis by RT-PCR.</p><p><b>RESULTS</b>OCTN2 mRNA was expressed in the caput, corpus and cauda of the epididymis.</p><p><b>CONCLUSION</b>The human epididymis may rely on OCTN2 for transporting L-Carnitine into the epididymal duct to promote sperm maturation. With the accumulation of information on OCTN2 in the human epididymis, OCTN2 will become a new molecular target for researches on male contraception.</p>

Study on the vertical transmission of Y chromosome microdeletions from father to son / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the Y chromosome microdeletions in the family of the infertile male and to study on the vertical transmission of Y chromosome microdeletions from father to son.</p><p><b>METHODS</b>The peripheral blood of infertile patients' family male members was extracted and analyzed with modified multiplex PCR. The infertile family tree was drawn according to the results.</p><p><b>RESULTS</b>Two cases in twelve investigated families had azoospermia factor (AZFc) microdeletion heredity. The others had no heredity.</p><p><b>CONCLUSION</b>AZFc microdeletion of the Y chromosome can be transmitted to the male offspring naturally,and the same deletion can result in different phenotypes in different individuals.</p>

Screening for Y chromosomal microdeletions in AZF region with modified multiplex PCR / 中华男科学杂志

<p><b>OBJECTIVE</b>Screening for Y chromosomal microdeletions in azoospermia factor (AZF) region with modified multiplex PCR.</p><p><b>METHODS</b>160 cases with spermatogenetic failure were recruited in the experimental group, while 90 cases of donors in controls. According to the laboratory guidelines supported by European Academy of Andrology (EAA) and European Molecular Genetics Quality Network (EMQN), Y chromosomal microdeletions in AZFa, b, c regions were screened with multiplex PCR. The primers of sequence targeted sites (STSs) and conditions of PCR were modified.</p><p><b>RESULTS</b>Using modified multiplex PCR, 14 (8.75%) cases with Y chromosomal microdeletions were found in the experimental group, while no case in controls. There were 12 cases in AZFc, 1 case in AZFa + b + c, 1 case in AZFb + c. According to statistics, the difference between two groups was significant (P <0.001). Reaction products could be clearly separated with agarose gel and finished in 1 h.</p><p><b>CONCLUSION</b>Modified multiplex PCR protocols supported by EAA and EMQN proved to be very accurate, sensitive and quick, which could be put into screening practice for Y chromosomal microdeletions in AZF region.</p>

A controlled randomized trial of the use of combined L-carnitine and acetyl-L-carnitine treatment in men with oligoasthenozoospermia / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine the efficacy and safety of combined L-carnitine and acetyl-L-carnitine therapy in infertile males with oligoasthenozoospermia.</p><p><b>METHODS</b>One hundred fifty patients with oligoasthenozoospermia were randomized selected into treatment and control groups. The treatment group with 90 patients were given L-carnitine (2 g/d) and acetyl-L-carnitine (1 g/d) orally, twice a day. The patients in control group were given Vitamin E 100 mg plus Vitamin C 100 mg, tid. The oral therapy lasted three months and patients accepted sperm analysis every one month. The L-carnitine level in seminal plasma was examined by high performance liquid chromatography (HPC). Side effects as well as pregnant rate were observed.</p><p><b>RESULTS</b>In the treatment group, 85 patients out of 90 finished the three month treatment. Female spouses of 10 patients (11.6%) achieved pregnancy. Moreover, their forward motile sperm per ejaculation, total motile sperm, as well as the concentration of L-carnitine in seminal plasma were increased significantly (P < 0.01). In control group, 53 patients out of 60 completed three months therapy. Two pregnancy (3.7%) was observed. Though some increase was seen in number of forward motile sperm and total motile sperm per ejaculation, the changes were not statistically significant (P > 0.05). The difference of the pregnant rate between two groups was statistically significant. No side effects were found.</p><p><b>CONCLUSION</b>Combined treatment with L-carnitine and acetyl-L-calmitine can be an effective and safe option for treating oligoasthenozoospermia by means of significantly improving forward motile sperm and total motile sperm per ejaculation, as well as increasing pregnant rates.</p>