血清瘦素、鸢尾素、SHBG、AQP8与PCOS不孕症接受IVF-ET患者激素水平和妊娠结局的关系研究

摘要 目的：研究血清瘦素、鸢尾素、性激素结合球蛋白（SHBG）、水通道蛋白8（AQP8）与多囊卵巢综合征（PCOS）不孕症接受体外受精-胚胎移植（IVF-ET）患者性激素水平和妊娠结局的关系。方法：选取2020年1月～2022年1月我院收治的293例接受IVF-ET的PCOS不孕症患者,根据是否临床妊娠成功将其分为临床妊娠失败组（n=118）和临床妊娠成功组（n=175）。收集患者临床资料,检测血清瘦素、鸢尾素、SHBG、AQP8水平。Pearson相关系数分析PCOS患者不孕症血清瘦素、鸢尾素、SHBG、AQP8水平与性激素水平的相关性,多因素Logistic回归分析PCOS不孕症接受IVF-ET患者妊娠结局影响因素,受试者工作特征（ROC）曲线分析血清瘦素、鸢尾素、SHBG、AQP8水平单独及联合预测PCOS不孕症接受IVF-ET患者临床妊娠失败的价值。结果：与临床妊娠成功组比较,临床妊娠失败组促卵泡生成素（FSH）、促性腺激素（Gn）用量、获卵数、受精率、优胚率、SHBG水平降低,黄体生成素（LH）、LH/FSH、睾酮（T）、胰岛素抵抗指数（HOMA-IR）、瘦素、鸢尾素、AQP8水平升高。Pearson相关系数显示,PCOS不孕症患者血清瘦素、鸢尾素、AQP8与FSH水平呈负相关,与LH、LH/FSH、T水平呈正相关（P均＜0.05）;SHBG与FSH水平呈正相关,与LH、LH/FSH、T水平呈负相关（P均＜0.05）。多因素Logistic回归分析显示,LH/FSH、T、HOMA-IR、瘦素、鸢尾素、AQP8为PCOS不孕症接受IVF-ET患者临床妊娠失败的危险因素,优胚率、SHBG为保护因素（P均＜0.05）。ROC曲线显示,血清瘦素、鸢尾素、SHBG、AQP8水平联合预测PCOS不孕症接受IVF-ET患者临床妊娠失败的曲线下面积（AUC）大于各指标单独预测。结论：血清瘦素、鸢尾素、SHBG、AQP8水平与PCOS不孕症接受IVF-ET患者FSH、LH、LH/FSH、T水平和临床妊娠失败相关,有助于预测PCOS不孕症患者妊娠结局。     

Discovery of substituted benzamides as follicle stimulating hormone receptor allosteric modulators

Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a pivotal role in the stimulation of follicular development and maturation. Multiple injections of protein formulations are used during clinical protocols for ovulation induction and for in vitro fertilization that are followed by a selection of assisted reproductive technologies. In order to increase patient convenience and compliance several research groups have searched for orally bioavailable FSH mimetics for innovative fertility medicines. We report here the discovery of a series of substituted benzamides as positive allosteric modulators (PAM) targeting FSHR. Optimization of this series has led to enhanced activity in primary rat granulosa cells, as well as remarkable selectivity against the closely related luteinizing hormone receptor (LHR) and thyroid stimulating hormone receptor (TSHR). Two modulators, 9j and 9k, showed promising in vitro and pharmacokinetic profiles.     

男性不育患者精液生殖细胞微核率的观察

本文研究人类精液中幼稚生殖细胞的微核率和男性不育的关系。在31例病人中,11例为无精症或多精症患者,其精液缺乏幼稚生殖细胞而未能进行微核测定。在其余的20例中,微核率最高可达122‰,最低为16‰。其中9例的微核率与对照组相比有显著升高,高微核率往往还伴随有减数分裂不分离以及出现高比例的二倍体及四倍体精子。还讨论了生殖细胞微核率增高作为不育症的一个可能病因以及微核测定的临床使用价值。     

Psychosocial stress and infertility

Experimental, theoretical, psychological, and economic barriers have caused physicians to rely on biomedical treatments for infertility at the exclusion of more environmentally oriented ones (e.g., psychosocial stress therapy). An evolutionary model is described for the origin of reproductive failure, suggesting why mammals evolved to be reproductively responsive to the environment and why psychosocial stress should have an especially strong impact on fertility problems. A study of the causal role of psychosocial stress in infertility is then summarized. The paper concludes with implications for future directions for the treatment of infertility and related human reproductive problems.     

Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species

Background

Reactive oxygen species (ROS) plays a major role in the pathology of male infertility. It is an independent biomarker of sperm function. Seminal plasma is a natural reservoir of antioxidants responsible for the nourishment, protection, capacitation, and motility of sperm within the female reproductive tract resulting in successful fertilization and implantation of the embryo. A comparative proteomic analysis of seminal plasma proteins from fertile men and infertile men with varying levels of ROS was carried out to identify signature proteins involved in ROS-mediated reproductive dysfunction.

Methods

A total of 42 infertile men presenting with infertility and 17 proven fertile donors were enrolled in the study. ROS levels were measured in the seminal ejaculates by chemiluminescence assay. Infertile men were subdivided into Low ROS (0–<93 RLU/s/10⁶ sperm; n = 11), Medium ROS (>93–500 RLU/s/10⁶ sperm; n = 17) and High ROS (>500 RLU/s/10⁶ sperm; n = 14) groups and compared with fertile men (4–50 RLU/s/10⁶ sperm). 4 subjects from fertile group and 4 each from the Low, Medium and High ROS were pooled. 1D gel electrophoresis followed by in-gel digestion and LC/MS–MS in a LTQ-Orbitrap Elite hybrid mass spectrometer system was used for proteome analysis. Identification of differentially expressed proteins (DEPs), their cellular localization and involvement in different pathways were examined utilizing bioinformatics tools.

Results

The results indicate that proteins involved in biomolecule metabolism, protein folding and protein degradation are differentially modulated in all three infertile patient groups in comparison to fertile controls. Membrane metallo-endopeptidase (MME) was uniformly overexpressed (>2 fold) in all infertile groups. Pathway involving 35 focus proteins in post-translational modification of proteins, protein folding (heat shock proteins, molecular chaperones) and developmental disorder was overexpressed in the High ROS group compared with fertile control group. MME was one of the key proteins in the pathway. FAM3D was uniquely expressed in fertile group.

Conclusion

We have for the first time demonstrated the presence of 35 DEPs of a single pathway that may lead to impairment of sperm function in men with Low, Medium or High ROS levels by altering protein turn over. MME and FAM3D along with ROS levels in the seminal plasma may serve as good markers for diagnosis of male infertility.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9094-5) contains supplementary material, which is available to authorized users.     

三种方法诊断不孕症患者子宫内膜息肉的临床价值研究

目的:探讨单用阴道超声(TVS)、子宫输卵管造影(HSG)、超声子宫水造影(SIS)以及三种方法联合诊断不孕症患者子宫内膜息肉(EP)的临床价值。方法:以206例行宫腔镜联合诊刮或病检的不孕症患者为研究对象,回顾性分析各种检查方法对EP的筛查结果,评价各种检查方法的真实性、可靠性以及预测值。结果:206例不孕症中,共确诊EP患者60例,阳性率29.1%。三种检查方法中,TVS的灵敏度最高(70.0%),特异度最低(73.3%),漏诊率最低(30.0%),误诊率最高(26.7%),正确诊断指数最高(43.3%),阴性似然比最小(0.409),阴性预测值最高(85.6%);SIS检查的灵敏度最低(38.7%),漏诊率最高(61.3%),但是特异性最高(93.3%),误诊率最低(6.7%),阳性似然比最大(4.284),阳性预测值最大(66.6%),正确诊断指数最低(32.0%);HSG检查的上述各项评价指标均介于TVS和SIS之间。TVS和SIS与金标准的符合率低,Kappa值均小于0.4;HSG符合率最高(86.2%),Kappa值0.647。三种检查联合诊断的灵敏度89.3%,漏诊率10.7%,特异度91.4%,误诊率8.6%,正确诊断指数80.7%,阳性似然比10.384,阴性似然比0.117,符合率89.3%,Kappa值0.792,阳性预测值83.3%,阳性预测值94.6%。结论:对于宫腔可能存在内膜息肉的不孕症患者,单一采用阴道超声检查、子宫输卵管造影或超声子宫水造影方法的灵敏度均较低,漏诊率高,与金标准的一致性较差,而三种方法联合用于诊断不孕症患者EP的真实性、可靠性及预测值均较好。     

Sialidases on Mammalian Sperm Mediate Deciduous Sialylation during Capacitation

Sialic acids (Sias) mediate many biological functions, including molecular recognition during development, immune response, and fertilization. A Sia-rich glycocalyx coats the surface of sperm, allowing them to survive as allogeneic cells in the female reproductive tract despite female immunity. During capacitation, sperm lose a fraction of their Sias. We quantified shed Sia monosaccharides released from capacitated sperm and measured sperm sialidase activity. We report the presence of two sialidases (neuraminidases Neu1 and Neu3) on mammalian sperm. These are themselves shed from sperm during capacitation. Inhibiting sialidase activity interferes with sperm binding to the zona pellucida of the ovum. A survey of human sperm samples for the presence of sialidases NEU1 and NEU3 identified a lack of one or both sialidases in sperm of some male idiopathic infertility cases. The results contribute new insights into the dynamic remodeling of the sperm glycocalyx prior to fertilization.     

Mitochondrial DNA mutations and male infertility

Infertility can be defined as difficulty in conceiving a child after 1 year of unprotected intercourse. Infertility can arise either because of the male factor or female factor or both. According to the current estimates, 15% of couples attempting their first pregnancy could not succeed. Infertility is either primary or secondary. Mitochondria have profound effect on all biochemical pathways, including the one that drivessperm motility. Sperm motility is heavily dependent on the ATP generated by oxidative phosphorylation in the mitochondrial sheath. In this review, the very positive role of mitochondrial genome's association with infertility is discussed.     

Impact of bariatric surgery on androgen profile and ovarian volume in obese polycystic ovary syndrome patients with infertility

Obesity has major adverse effects on reproductive performance and fertility potential especially in women with polycystic ovary syndrome. In this study, we aimed to evaluate the consequences of excess weight reduction by bariatric surgery on androgen levels, and ovarian volume by ultrasonography in obese polycystic ovary patients. This one year Cohort study was carried out in Zagazig university hospitals. The study included 36 infertile women with PCOS and obesity, who underwent bariatric surgery(sleeve gastrectomy or gastric bypass). Patients were evaluated for free and total serum testosterone levels, Sex hormone binding globulin (SHBG), free androgen index (FAI) and also ovarian volume by ultrasound pre-operatively, 6 months and 1 year after surgery. The results showed significant reduction in Body Mass Index, free and total serum testosterone levels and rise in SHBG and regulation of menstrual cycle at 6 and 12 months after operation. Free androgen index and ovarian volume by ultrasound also significantly decreased (p < 0.001) .As a conclusion, Bariatric surgery results in durable loss of weight and restores the normal physiological balance of androgenic milieu and ovarian morphology by ultrasound, in infertile women who have Polycystic ovary syndrome.