| Chapter one:Clinical study on the comparison of testicular function of different types of primary varicocele and the outcome after operationBackground:Varicocele(VC)refers to spermatic vein flow obstruction or reflux,which may contribute to abnormal elongation,expansion and circuity of the pampiniform plexus of the spermatic vein.Varicocele patients may present palpable or visible circuity of the pampiniform plexus of the spermatic vein when it dilates to some extent,and they can feel discomfort or pain in scrotum and face risk of progressive decline of spermatogenic function.Varicocele has become the main cause of male infertility.There are various types of classification according to different classify methods.According to the location,varicocele can be divided into left varicocele,right varicocele and bilateral varicocele while the first one is the most common one as the incidence is about 77%?92%,and 10%(7%?22%)for bilateral varicocele,while isolated right varicocele is rare.According to age,varicocele can be divided into adolescent varicocele and adult varicocele.And it can be divided into primary varicocele and secondary varicocele according to the causes.The causes of the primary VC is not clear,which is generally believed to be closely related to the anatomical factors and dysplasia,whose symptoms can be aggravated after long-time standing,walking or exercise and alleviated by lying flat to rest.And the secondary varicocele is due to the compression on the spermatic vein caused by abdominal cavity tumor,hydronephrosis or ectopic vessel,whose symptoms cannot be relieved by lying flat to rest.According to the severity,it can be divided into clinical varicocele and subclinical varicocele while the latter one refers to the mild varicocele which cannot be found by physical examination,but can be found by ultrasound or other auxiliary examinations.The accidence of varicocele in healthy men is about 10%?15%,and it is 30%?40%in primary infertile men and 69%?81%in secondary infertile men.What's more,25.4%of men with abnormal semen suffer from varicocele.As for adolescent,the incidence of varicocele is 14%-20%.A recent study including 7035 European,whose average age is 19,shows that the accidence of varicocele is 15.7%.Besides,a study points out that the accidence increases in first-degree relatives of VC patients,indicating that VC has some familial aggregation.The etiology of varicocele is closely related to anatomy.Firstly,the absence or dysfunction of spermatic vein valve may result in blood reflux in spermatic vein.Secondly,the wall of the spermatic vein and its surrounding connective tissue or cremaster muscle may be weak.Thirdly,long-time standing may contributes to spermatic vein flow obstruction.The reason for higher incidence of left VC may be as following:(1)The right internal spermatic vein terminates directly into the low-pressure inferior vena cava while on the left side,it joins with the relatively high-pressure left renal vein.(2)Left renal vein may be pressed by superior mesenteric artery and abdominal aorta,which result in spermatic vein flow obstruction or reflux(so-called nutcracker phenomenon).(3)Sigmoid colon may press left internal spermatic vein at the front.(4)The absence of spermatic vein valve is more common on the left.Varicocele-caused decline of spermatogenic function is a complex pathological procedure,which may be the result of different factors.Cozzolino M et al managed a research including 5680 Italians and found that sperm quality is significantly correlated with age.A large study found that total sperm count,morphology and motility will decrease with age increasing,and a relation between semen quality and VC grade was described.Vivas-Acevedo G et al yielded similar results.A study including 715 samples indicated that smoking more than 10 cigarettes per day showed negative effects on semen morphology and motility,this result may help in persuading varicocele patients to stop smoking in order to improve semen quality.A study implemented by Fariello RM et al reported that smoking could deteriorate semen quality and damage sperm DNA integrity in VC patients.Other factors such as VC grade,also,have been investigated.A study showed that the higher VC grade was,the worse semen quality would be.Another study indicated that testicular volume discrepancy had a higher incidence in VC patients,and semen quality got worse with bigger testicular volume discrepancy.Diamond et al also reported a negatively association between testicular atrophy index and semen quality.Besides,more and more evidences convincing that inhibin B is correlated with semen quality in VC patients.A cross-sectional study including 7035 samples found that the serum inhibin B level in healthy people,grade I,grade II and grade III varicocele patients were 199 pg/ml,190 pg/ml,189 pg/ml and 171 pg/ml,indicating that inhibin B was negatively associated with varicocele grade.Moreover,Moazzam A et al reported that sperm DNA fragmentation was negatively related to semen concentration,motility and morphology.Osadchuk et al also found that deteriorated semen quality might be associated with damaged integrity of sperm DNA in VC patients.There are a variety of factors may influence semen quality,some of which remain controversial,so further studies are needed.Though VC patients are always asymptomatic,some may feel scrotal pain or suffer from infertility.VC patients can feel discomfort,heavy feeling,dragging or pain in scrotum,which can be aggravated after long-time standing,walking or physical exertion and alleviated by lying flat to rest.In varicocele patients,the incidence of scrotal pain is about 2%?10%.The etiology of scrotal pain associated with varicocele is not completely understood.Proposed mechanisms include compression of nearby neural fibers by the dilated venous complex,increased scrotal temperature,oxidative stress to the testicular parenchyma,and tissue ischemia secondary to venous stasis.When Conservative treatment fails to take effect,varicocelectomy becomes an important alternative.It's accepted that varicocelectomy is effective in relieving pain associated with varicocele.The success rate of pain resolution for varicocelectomy is about 61%?100%,which is above 85%in most studies.The success rate of pain relief is influenced by various factors,which remain controversial.What's more,some studies concluded that varicocelectomy improves semen quality,but it has no influence on natural pregnancy rate.On the other hand,a Cochrane system review pointed out that varicocele repair for infertile men can improve natural pregnancy rate.Another study indicated that bilateral is superior to unilateral varicocelectomy in infertile males with left clinical and right subclinical varicocele,which is associated with greater improvement in spontaneous pregnancy rate after the surgery.Whether varicocelectomy can improve pregnancy rate with improvement of semen quality remains controversial.Objective:By studying relation between the different types of primary varicocele and the BMI,testicular volume,testicular atrophy index,as well as the semen quality,the author think we can get clearer opinion on the damage of different types of primary varicocele,and get more reliable clues about studying VC's mechanism as well as more guide for diagnosis and treatment.In addition,searching predictors of pain resolution after varicocelectomy for painful varicocele is helpful to predict the operation effect and the prognosis,hence,provide evidences for the establishment of surgical indications.What's more,exploring whether varicocelectomy can improve testicular volume and semen quality and focusing on spontaneous pregnancy rate and childbirth rate may help in evaluating the therapeutic effect of surgery and providing evidences for potential next step of treatment.Methods:We implemented a retrospective study by searching electronic medical record system for patients who went through varicocelectomy in our hospital from December 2014 to December 2016.Inclusion criteria included:grade ? or grade? varicocele which is confirmed by ultrasound.All patients should meet varicocelectomy indications.Exclusion criteria included:(1)secondary varicocele;(2)other possible diseases affecting semen quality or resulting in scrotal pain(chronic pelvic pain syndrome,chronic prostatitis,hydrocele,mumps,cryptorchidism,testicular tumor,epididymitis,orchitis,history of pelvic radiation or chemotherapy etc);(3)history of varicocelectomy.Firstly enquired about all the patients' detailed medical history and managed physical examination on them.Did further scrotal ultrasound to those suspected varicocele for diagnosis.Those who were in accordance with surgery indications would be suggested taking operation.On the day of patients' admitting,everyone would be enquired about detailed history and measured the height and weight.If the patient felt scrotal pain,he would be evaluated the pain degree by visual analog pain score(VAS).At the second day,they would be extracted the elbow venous blood for inspection about blood routine,blood biochemistry,hormone analysis,preoperative four,urine routine,stool routine,and completed the other routine examinations such as electrocardiogram,chest X-ray.The semen analysis required the patient to get semen by masturbation into a sterile container after 2?7 days of abstinence,and then tested by the SQA-V full-automatic semen analysis under the instruction of the fifth edition of WHO Lab Testing Manual of Human Semen.Generally speaking,the surgery would be performed on the second day,and patients discharged 1-2 days after surgery.Because it takes about 3 months for semen to mature,patients were informed with detailed instructions about postoperative follow-up that return to do the physical examination,ultrasound and semen analysis after 3 to 6 months.If the patient felt scrotal pain before surgery,he would be called back 1 year after surgery,their response was graded as a complete response(pain was completely absent after surgery),partial response(pain persisted but was reduced after surgery)and no response(pain remained unchanged after surgery).And infertile patients were called back for spontaneous pregnancy rate and childbirth rate within a year postsurgery.All the data was collected and organized by the EXCEL 2007 software,and then calculated left testicular volume(LTV),right testicular volume(RTV),total testicular volume(TTV)and testicular atrophy index(TAI).Testicular volume was measured ultrasonographically using the formula:0.71 × length × width × height.Testicular atrophy index was measured with the formula:(RTV-LTV)/RTV × 100%.SPSS 22.0 statistical software was used to do statistical analyses on the comparison of testicular function of different complaints and different ages of primary varicocele,and the analysis parameters was including BMI,RTV,LTV,TTV,TAI,semen quality parameters(semen volume,sperm concentration,total sperm count,sperm survival rate,total sperm motility and sperm deformity rate).Normal distribution data is expressed as X±s.Three groups of independent samples were compared by one-way ANOVA and multiple comparisons were managed by LSD.The probability values are two-sided;a probability of less than 0.05 was considered to indicate statistical significance.And then a multinomial logistic was used to find predictors of pain resolution after varicocelectomy,dependent was set as pain resolution,and factors were set as age,BMI,duration of pain,type of varicocele ligation,duration of ligation,blood loss,RTV,LTV,TTV,TAI,semen volume,sperm concentration,total sperm count,sperm survival rate,sperm deformity rate,sperm progressive motility rate and total sperm motility.Parameters before and after surgery were compared by paired-samples t test.Results:(1)As for different complaints,patients of infertile group were significantly older than discomfort group and asymptomatic group(P=0.006,P=0.009).The BMI of infertile group was significantly higher than that of discomfort group(P=0.030).The sperm survival rate of infertile group was significantly lower than that of discomfort group and asymptomatic group(P=0.000,P=0.001).The sperm deformity rate of infertile group was significantly higher than that of discomfort group(P=0.009).The sperm progressive motility rate of infertile group was significantly lower than that of discomfort group and asymptomatic group(P=0.000,P=0.000).The total sperm motility of infertile group was significantly lower than that of discomfort group and asymptomatic group(P=0.000,P=0.000).(2)As for different age,the BMI of patients aged 18-29 was significantly lower than that of patients aged 30-39 and aged 40-49(P=0.001,P=0.018).The sperm survival rate of patients aged 18-29 was higher than patients aged 30-39 and aged 40-49(P=0.045,P=0.021).The total sperm motility of patients aged 18-29 was significantly higher than that of patients aged 40-49(P=0.020).(3)As for predictors of pain resolution after varicocelectomy for painful varicocele,there were totally 64 patients who went through varicocelectomy and underwent followed up.38(59.4%)of these patients got complete response,and 23(35.9%)of these patients got partial response,only 3(4.7%)of these patients got no response,the total rate of pain relief was 95.3%.Of these patients,49(76.6%)went through Palomo operation,7(10.9%)had microscopic varicocelectomy,and 8(12.5%)had laparoscopic varicocelectomy.As for ultrasonic grade,5(7.8%)men had subclinical varicocele,27(42.2%)men had grade I varicocele,20(31.3%)had grade II varicocele,and 12(18.8%)men had grade III varicocele.By multinomial logistic,the study found that pain duration was significantly related to the success rate of pain relief(P<0.05).The study used complete response as control,and then established statistical models of other response grade.Compared with complete response,there is greater risk of partial response with longer duration of pain(OR=1.035,95%CI:1.004?1.067).And there is no significant relation between duration of pain and no response.The total validity of the model is 67.2%.(4)As for parameters before and after surgery,semen volume(P=0.003),total sperm count(P=0.001),sperm survival rate(P=0.000),sperm progressive motility rate(P=0.001)and total sperm motility(P=0.000)were significantly improved after varicocelectomy,sperm deformity rate(P=0.011)decreased as well.As for varicocele infertile men,TAI(P=0.030)significantly decreased after surgery,meanwhile sperm survival rate(P=0.002),sperm progressive motility rate(P=0.001)and total sperm motility(P=0.001)were statistically improved.The spontaneous pregnancy rate is 26.1%and childbirth rate is 21.7%within a year postsurgery.Conclusions:Patients of infertile group were significantly older than discomfort group and asymptomatic group.The BMI of infertile group was significantly higher than that of discomfort group.The testicular volume and testicular volume discrepancy did not differ between different complaints.Values for almost all semen parameters were worse in infertile group than in discomfort group and asymptomatic group.We should take active management for infertile varicocele patients in order to improve testicular spermatogenic function and fertility.The BMI of patients aged 18-29 was significantly lower than that of patients aged 30-39 and aged 40-49.There was no significant difference in testicular volume and testicular volume discrepancy between different ages.And semen quality got worse as age increased.There was no association between BMI,varicocele grade,type of varicocele ligation,semen quality and pain relief after surgery,and only duration of pain may predict outcomes in varicocele patients.Higher rate of complete response was related to shorter duration of pain.But predictors of pain resolution after varicocelectomy for painful varicocele still need prospective,large-sample and multicenter randomized controlled trials to investigate.Besides,varicocelectomy can improve semen count,morphology and motility.As for varicocele infertile men,varicocelectomy may improve testicular volume and reduce TAI as well.Chapter two:The relationship between inhibin B and varicocele:an updateInhibin B is a glycoprotein mainly produced by testicular Sertoli cell that preferentially suppresses the production and secretion of FSH in pituitary and is related to spermatogenesis.Varicocele refers to the abnormal circuity and expansion of the pampiniform plexus of the spermatic vein,and it contributes to spermatogenic dysfunction and becomes the most common cause of infertility.More and more evidence convince that serum inhibin B is negatively correlated with the severity of varicocele,and testing serum inhibin B can evaluate the severity of spermatogenic dysfunction in varicocele patients and also assess the effect of varicocele repair on spermatogenesis,thus has potential application in the diagnosis and treatment of varicocele. |
PDF Full Text Request