Globozoospermia, characterized by round-headed spermatozoa without acrosomes, is a rare and severe teratozoospermia causing primary male infertility. Homozygous DPY19L2 deletions have been identified as the main cause of globozoospermia, blocking sperm head elongation and acrosome formation. Several previous studies showed a very different prevalence of DPY19L2 gene deletions among globozoospermic patients in cohorts with different sample sizes and in different ethnic background. And all the patients previously analyzed were mainly of European, North African and Middle Eastern origins. So far, only 11 different point mutations of the DPY19L2 gene have been reported. To investigate the prevalence of DPY19L2 gene mutations in Chinese patients with globozoospermia and whether we can identify new sequence variants in this study, we recruited a total of 16 globozoospermic patients. Excluding one of two brothers, molecular analysis for deletions and mutations in the DPY19L2 gene was performed on 15 genetically independent individuals. Four of the 15 genetically independent patients with globozoospermia were homozygous for the DPY19L2 deletion, 5 were homozygous for a point mutation including a nucleotide deletion c.1532delA (two patients), a multi-mutation consisting of a nucleotide deletion c.1679delT and a two-nucleotide deletion c.1681_1682delAC (c.[1679delT; 1681_1682delAC]) (one patient), a recurrent missense mutation R290H (one patient) and a missense mutation L330P (one patient). One additional patient had a heterozygous deletion in one allele but with no mutation identified in another allele. Overall, 60% of the patients (9/15) have a sequence variant of DPY19L2 in both alleles. This study confirms that the DPY19L2 mutations are the major cause of globozoospermia. Three novel point mutations and a recurrent missense mutation were found in this study, further broadening the spectrum of DPY19L2 mutations.

Abstract:With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.

We identified loss-of-function PV of ZP2 causing a structurally abnormal and dysfunctional ZP, resulting in fertilization failure and female infertility.

BackgroundThe genetic causes for most male infertility due to severe asthenozoospermia remain unclear.ObjectiveOur objective was to identify unknown genetic factors in 47 patients with severe asthenozoospermia from 45 unrelated Chinese families.MethodsWe performed whole exome sequencing of 47 individuals with severe asthenozoospermia from 45 unrelated families. Mutation screening was performed in a control cohort of 637 individuals, including 219 with oligoasthenospermia, 195 with non-obstructive azoospermia and 223 fertile controls. Ultrastructural and immunostaining analyses of patients’ spermatozoa were performed to characterise the effect of variants.ResultsOne homozygous non-sense mutation (NM_194302, c.G5341T:p.E1781X), two compound heterozygous mutations (c.C2284T:p.R762X and c.1751delC:p.P584fs) and two compound heterozygous mutations (c.5714_5721del:p.L1905fs and c.C3021A:p.N1007K) were identified in CFAP65 of three individuals with completely immotile spermatozoa, respectively. No biallelic deleterious variants of CFAP65 were detected in the control cohort of 637 individuals. Ultrastructural and immunostaining analyses of spermatozoa from two patients showed highly aberrant sperm morphology with severe defects such as acrosome hypoplasia, disruption of the mitochondrial sheath and absence of the central pair complex.ConclusionTo the best of our knowledge, we are the first to report that CFAP65 mutations may cause spermatozoa to be completely immotile.

Purpose:To compare the effectiveness of double IUI with single IUI in male factor and idiopathic infertility patients undergoing controlled ovarian hyperstimulation (COH). Methods: A prospective randomized study of 1257 COH-IUI cycles was performed. Total 1270 patients with mild or moderate male factor infertility (n = 776) and idiopathic infertility (n = 494) were enrolled in this study, and 767 with male factor infertility and 490 with idiopathic infertility completed clomiphene citrate (CC)/human menopausal gonadotrophin (hMG) COH cycles and IUI. Categorized on the basis of the causes of infertility (male factor, M; idiopathic infertility, I), patients were randomized into one of the following groups: Single IUI group (M 1 /I 1 ) received single insemination 34 h post hCG administration, and double IUI group (M 2 /I 2 ) received two inseminations 18-24 and 36-48 h post hCG injection, respectively. Results: The overall pregnancy rates were 15.43%. Pregnancy rate for single and double IUI group was 11.06 and 19.87% (p < 0.05), respectively. There was a significant statistical difference in cycle fecundity between M 1 and M 2 group (11.34% vs. 24.93%, p < 0.05), and between I 2 and M 2 group (11.93% vs. 24.93%, p < 0.05), but there was no significant difference between I 1 and I 2 (10.53% vs. 11.93%, p > 0.05). Conclusions: Double IUI increases the pregnancy rate significantly in patients with male factor infertility, and single IUI acts as efficient as double IUI in patients with idiopathic infertility.KEY WORDS: Intrauterine insemination; male factor infertility; idiopathic infertility; prospective randomized study.

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Purpose To investigate whether serum Anti-Müllerian hormone (AMH) on day 3 could predict controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome. Methods A total of 164 PCOS patients undergoing their first IVF treatment cycle were prospectively included. Serum AMH levels on cycle day 3 was measured. The controlled ovarian stimulation and clinical outcomes for the study population were divided according to the <25th, 25 to 75th, or >75th percentile of serum day-3 AMH. Results Estradiol levels on hCG day and the number of retrieved oocytes significantly increased with increasing serum AMH levels, while total consumption of gonadotropin dose showed a significant decrease (P<0.05). Fertilization rate and the number of good quality embryos were comparable among the low, average and high groups (P>0.05). Embryo implantation rates in the high AMH group was significantly inferior to those with low and average AMH concentration (27 versus 48.8 and 50%, P<0.01). Clinical pregnancy rates was lower in the high AMH group than that of the low and average group (45.9 versus 65 and 66.7%, P00.09), but this difference was only close to statistical significance. In addition, ordinal regression analysis indicated that LH level was the only independent predictor of embryo implantation rates (P00.017). Conclusions In PCOS women, AMH levels on day 3 of the IVF stimulation cycle positively predict ovarian response to gonadotrophins. However, the women with high AMH levels had a significantly decreased IR, which may be due to remarkably increased LH concentrations.Keywords Anti-Müllerian hormone . Assisted reproduction . Polycystic ovary syndrome . Serum AMH Anti-Müllerian hormone (AMH), also known as Müllerian inhibiting substance (MIS), is producted specifically by granulose cells of early developing pre-antral and small antral follicles in the ovary, and declines with advancing age. AMH has therefore been proposed as a novel clinical marker of ovarian reserve [1]. Another major reason for the interest in AMH is the fact that serum AMH levels are increased significantly in women with polycystic ovary syndrome (PCOS) when compared with normoovulatory women [2,3].PCOS is the most frequent cause of anovulatory infertility and hyperandrogenism in young women [4]. Women with this syndrome are characterized by an excessive number of small antral follicles (2-3 fold that of normal ovaries) [5]. As an exclusively granulosa cell product, it was initially proposed that the rise in serum AMH in PCOS was a consequence of the increased small antral follicle number in these ovaries [6]. The Capsule In PCOS women, high AMH levels on day 3 of the IVF stimulation cycle predict high ovarian response to gonadotrophins, but low embryo implantation rates.

Empty follicle syndrome (EFS) is the complete failure to retrieve oocytes after ovarian stimulation. Although LHCGR and ZP3 were identified as causative genes, it is still unclear what happens to these patients’ oocytes, and the pathogenesis of EFS remains obscure. Here, we identified six novel ZP1 mutations associated with EFS and female infertility that was inherited recessively in five unrelated families. Studies in CHO-K1 cells showed that these mutations resulted in either degradation or truncation of ZP1 protein. Immunohistochemistry using ovarian serial sections demonstrated that all preantral follicles had normal architecture, but with a thin ZP, lacking ZP1, surrounding the growing oocytes. The antral follicles were also defective in normal cumulus–oocyte complex organisation, leading us to speculate that the lack of ZP1 might lead to oocyte degeneration or increased fragility of the oocyte during follicular puncture, ultimately resulting in EFS. To our knowledge, this is the first study that presents morphological evidence showing normal preantral folliculogenesis with abnormal ZP assembly in EFS patients. Our data provides a better understanding of the biological functions of ZP1 in human ZP assembly and folliculogenesis and gives new insights into the pathogenesis of EFS and possible therapeutic developments.