Secretory role for human uterodomes (pinopods): secretion of LIF

The differentiation of human endometrial epithelium is a dynamic event, which occurs throughout the menstrual cycle in preparation for pregnancy. The appearance of uterodomes (pinopods) in this regard was first introduced in rodents with an established pinocytotic function, whereas little evidence was available in humans in this context. This study was undertaken to identify the potential physiological roles of uterodomes in the implantation process. To address this, endometrial biopsies from early, mid- and late luteal phases of the menstrual cycle of 23 fertile female patients with regular menses were used. Scanning and transmission electron microscopies (SEM and TEM) as well as immunofluorescence and immunogold TEM were performed to study the morphological changes and the expression pattern of leukaemia inhibitory factor (LIF) at uterodomes. Our results illustrated a high level of LIF expression in the human uterodomes, which was colocalized with the well-known biochemical markers of exocytosis, including syntaxin-1, 25-kDa synaptosomal protein (SNAP-25) and vesicle-associated membrane protein-2 (VAMP-2). Our morphological and immunocytochemical findings illustrated a secretory function for human uterodomes for the first time. In conclusion, this novel function for uterodomes provides an important clue in detection of their physiological function(s) during the process of the plasma membrane transformation.     

Uterine contractility decreases at the time of blastocyst transfers

High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF-embryo transfer outcome. This prompted us to quantify prospectively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation, up to the time of blastocyst transfers, in 43 IVF-embryo transfer candidates. Contractility was assessed on the day of human chorionic gonadotrophin (HCG) administration, 4 days after HCG (non-cavitating embryo transfer; HCG + 4), and 7 days after HCG (blastocyst transfers; HCG + 7). For this, 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency. Our results indicated that a slight, yet significant, decrease in uterine contraction frequency, observed from the day of HCG (4.4 +/- 0.2 contractions/min) to HCG + 4 (3.5 + 0.2 contractions/min), was followed by a more pronounced, additional decrease between HCG + 4 and HCG + 7 (1.5 +/- 0.2 contractions/min; P < 0.001). In conclusion, during the luteal phase of ovarian stimulation, uterine contractility decreases progressively, and reaches a nearly quiescent status 7 days after HCG administration, at the time of blastocyst transfers. It is possible that such a uterine relaxation assists blastocyst implantation.     

Continuous administration of gonadotrophin-releasing hormone agonist during the luteal phase in IVF

BACKGROUND: It has been reported that ceasing the administration of gonadotrophin-releasing hormone (GnRH) agonist causes a profound suppression of circulating serum gonadotrophins. A comparative prospective and randomized study was conducted to investigate the effect of continuous administration of GnRH agonist during the luteal phase in an ovarian stimulation programme for IVF. METHODS: GnRH agonist was administered intranasally from the midluteal phase of the previous cycle, and pure FSH administration started on cycle day 7. In the continuous-long protocol (cL) group (n = 161 ), GnRH agonist administration was continued until 14 days after oocyte retrieval. In the long protocol (L) group (n = 158 ), GnRH agonist was administered until the day before human chorionic gonadotrophin (HCG) administration. RESULTS: The implantation rate and live birth rate per unit of transferred embryos were significantly higher in the cL group than the L group (P < 0.05 ). Serum LH and FSH concentrations on the day of, and 1 day after, HCG administration were significantly lower in the L group than the cL group (P < 0.01 ). CONCLUSIONS: Continuation of GnRH agonist administration during the luteal phase might facilitate implantation, and prevent the profound suppression of serum gonadotrophins.     

中药单体调控自噬干预胚胎植入的研究进展

胚胎植入是生殖过程中最关键的步骤之一,植入失败的胚胎无法继续发育,是导致不孕的重要原因之一。胚胎植入的成功依赖于子宫内膜的高容受性和具有植入能力的胚胎。自噬是细胞质、细胞器和内含物被双膜囊泡吸收并运输到溶酶体进行降解和再循环的过程,是一种维持内环境稳态的方式。大量证据表明,自噬在胚胎植入的各个环节有着重要的作用。基于此探讨了自噬与子宫内膜容受性和胚胎植入能力的关系,并根据最新的研究进展,梳理了大黄素、梓醇、芍药苷、白藜芦醇、叶酸、玉米赤霉烯酮、姜黄素、汉黄芩素、槲皮素、白杨素、小檗碱、芹菜素、菲西汀、山柰酚在内的14种中药单体调控自噬干预胚胎植入的不同环节的5个机制,包括促进子宫内膜基质细胞蜕膜化、促进细胞凋亡、调节激素水平、协调炎症、促进排卵,希望对今后中药单体提高胚胎植入的成功率提供参考及思路。     

卵裂期胚胎可溶性人类白细胞抗原G与妊娠结局的关系

目的探讨卵裂期胚胎培养液中可溶性人类白细胞抗原G(sHLA-G)表达与胚胎发育和妊娠结局的关系。方法选择2017年5月—2018年5月在江苏省苏北人民医院生殖医学中心接受冻融胚胎移植的86例不孕患者,共计100个周期为研究对象。根据妊娠结局分为妊娠组和未妊娠组,采取回顾性分析方法,比较两组基本信息及sHLA-G含量差异;再根据sHLA-G的测定结果分为sHLA-G阳性组及阴性组,比较两组的植入率。采用酶联免疫吸附实验(ELISA)检测卵裂期胚胎(体外培养第三天)培养液中sHLA-G浓度。结果妊娠组sHLA-G平均值高于非妊娠组,组间差异有统计学意义(P<0.05);sHLA-G阳性组的sHLA-G含量平均值及植入率均大于sHLA-G阴性组,差异有统计学意义(P<0.05);二元Logistic回归分析结果显示,胚胎培养液中sHLA-G含量为影响胚胎植入的独立危险因素(P<0.05)。结论第三天胚胎培养液中sHLA-G的表达及表达量与胚胎植入有关,可作为妊娠结局的预测指标。     

不同影像技术对胰腺癌模型兔原位种植建模效果的评价与比较

目的:比较CT、MRI及超声平扫检查对胰腺癌模型兔建模效果的评价价值。方法:建立胰腺癌模型兔10只,对每只模型兔采用CT、MRI、超声平扫等影像检查,比较不同影像技术对模型兔肿瘤病灶的检出率;并对肿瘤采用磁共振波谱(MRS)分析肿瘤代谢情况。结果:建模成功3周末,死亡5只,存活5只;3种检查方式均能发现胰腺区的肿瘤病变和腹腔积液,检出率均能够达到100%。在对肿大淋巴结和血管包绕的检出中,MRI与CT的检出率相当,均优于超声平扫;在对远处转移的检出中,MRI要优于另外两种方式,但三种影像检查方法的病灶肿大淋巴结、血管包绕及远处转移等检出率比较,差异均无统计学意义(χ²=3.619,χ²=3.000,χ²=6.857;P>0.05)。MRS分析能够清晰显示胆碱(Ch)、肌酐(Cr)和N-乙酰天门冬氨酸(NAA)峰。结论:对动物肿瘤模型采用CT、MRI和超声平扫检查,可以获得较为满意的检测效果,但是在行动物实验过程中,需要根据实际的肿瘤种植位置和肿瘤转移位置采用合适的影像检查方法。     

胎盘滞留96例临床分析

目的 积极预防和正确处理胎盘滞留,减少产后出血及产褥感染。方法 产后胎盘滞留时间较短的可以行人工剥离胎盘术。如用手剥离过程中发现宫壁与胎盘之间没有分界线或有草根样条索状连接时,可能有胎盘植入,需停止剥离,根据情况决策保守治疗或行子宫切除术。若产后胎盘滞留时间较长,有明显感染,再行清宫术。结果 96例产后胎盘滞留患,均痊愈出院。结论 落实好避孕措施,减少流产次数;提高引产,流产技术操作水平;正确处理第三产程等可有效预防胎盘滞留的发生。对于胎盘滞留,应根据不同情况给予相应的处理,可减少产后出血及产褥感染。     

The role of sperm in inducing genomic changes in the implantation: An experimental study

Endometrial receptivity and implantation are important topics in reproductive sciences. No evidence was found to support sperm involvement in endometrial receptivity and its associated factors. This study aimed to explore the effect of the normal human spermatozoa–endometrium cell interaction in regulating genes in the endometrial receptivity pathway. Semen samples were collected from a healthy and fertile man; then, they were incubated with endometrial cells for 24 hr and considered as the sperm group. A group was cultured without spermatozoa and considered as a control group. About 24 hr later, cells were collected from the bottom of the culture dish. The expressions of the VEGF, FGF2, HBEGF, LIFR, EGF, LIF, MUC1, HOXA10, CSF and PGR genes were evaluated in the two groups. Statistical analysis was performed using an independent sample test. Compared with the control group, in the sperm group, the mRNA levels of PGR (p = .0451), VEGF (p = .0101), HBEGF (p = .0163), EFG (p = .0339), FGF2 (p = .012), LIF (p = .0324), LIFR (p = .0321) and HOXA10 (p = .0098) were significantly upregulated. The results showed that there is a need for the interaction between spermatozoa and endometrium for implantation and can be used for preparing uterine in in vitro fertilisation cycles.     

Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

HbA1c over 8.5% is not predictive of increased infection rate following penile prosthesis implant surgery in diabetic patients with erectile dysfunction

Diabetes mellitus is associated with increased risk of erectile dysfunction. Penile prosthesis implantation is an efficient therapeutic option for erectile dysfunction, but not without risk, as infection remains a prominent concern. This study investigates diabetes mellitus as a risk factor for penile prosthesis implantation infection and the relationship between haemoglobinA1c levels and infection rates. All diabetic patients with erectile dysfunction who underwent penile prosthesis implantation surgery between January 2012 and November 2019 at Hamad Medical Corporation, Qatar, were included in this retrospective observational study. A total of 599 diabetic patients with erectile dysfunction had penile prosthesis implantation. Mean age was 59.69 ± 31.19. Penile prosthesis implantation infection rate was 0.83% (5/599), while the mean haemoglobinA1c level was 7.58 ± 1.45 mmol/l (range: 4.1–12.6). A comparison between diabetic patients with penile prosthesis implantation infection and those without infection revealed no significant difference in the level of haemoglobinA1c between the two groups with mean haemoglobinA1c in patients with infected implants 7.14 and 7.59 for noninfected (p = 0.491). Limitations include retrospective single-centre design and low-infection rates reducing sample number. Penile prosthesis implantation infection rate in a large series of diabetic patients was low with no significant association between haemoglobinA1c level and penile prosthesis implantation infection observed.