Slide show on ale subfertility by Prof S K Pal

MALE  FACTOR SUBFERTILITY

.(slide show by Prof. S K Pal-Kolkata)

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Prevalence:-  Males are entirely  responsible for subfertility in  1/3 rd of all subfertility problem, and is partly responsible for another  20% cases.    In total about 50% of all cases of subfertility males are involved.

 Normal Seminal Parameters:-  WHO Lab Manual(2010)- in App. A1.1 declares of all fertile men(whose partners were  able to conceive by 12 months of trying):- in 5% of such fertile men the seminal  criteria were Density = 15 million/ ml; 32% for good forward progression ( motility  within 60 minutes of  ejaculation,   and normal  morphology of 4%  . Such apparently suboptimal seminal parameters which will readily prompt us to jump for antioxidant therapy will refrain us from doing so after promulgation of W H O Manual. This study of WHO will offer an  anxiety free life to the couple for at least first few yrs of trying  if they are young and the concerned man , according to WHO can’t be just called  be infertile ,albeit may be called as substandard semen sample.

What are the common causes of male subfertility?

In about 50% of cases of male subfertility no obvious cause is detected. Possibly monogenic disorder .There is no watertight separation between different causes of which contributes to male subfertility. Thereby I mean many minor abnormality may lead to   1) OAT(oligozoospermia . 2)  asthenozoospermia, Teratozoospermia ) .

However = Nonobstructive azoospermia 30%; Idiopathic (no obvious cause-)-25%; testicular failure 9%, seminal disodreds-7%, Obstructive azoospermia-6%; Cryptorchidism-6%., MAGI(Male Accessory Gland Infections)

 Basically there are three   types of diseases which can be clinically diagnosed. Such are A) complete absence of sperms in the ejaculated semen-azoospermia B) Sperms are present but their quality or quantity is far less to yield fertilization and to develop embryonic competency and successful pregnancy. C) The third group is that male sexual disorders where the male partner is unable to deposit semen at the right time of fertile period.

 

Type 1 Male Infertility:: -Absence of sperms (Azoospermia):- 1) Primary Testicular Failure-this occurs during intra uterine life i.e. development process. In such cases FSH will be high. This is the most common cause of azoospermia.  One subtype of this is  a syndrome called TDS=Testicular Dysgenesis Syndrome- which lead to low or absent sperms. Cryptorchidism, Hypospadias are other rare causes -.Therefore pregnant mothers  should maintain optimal health so that the foetus inside womb grow properly.

2) Genetic diseases so that sperm production is interfered . In fact this is the  most common cause of azoospermia) 3) Idiopathic (cause not known inspite of several investigations), 4) Hypothalamic-Pituitary Diseases (Primary hypogonadism). Additionally, following diseases can lead to absence production of sperms in the testis e.g. Testicular Dysfunction Syndrome, Maldescent of testis, Torsion of testis, Viral and bacterial infections, Chemotherapy and radiation.

 

Testicular Dysfunction Syndrome (not to be confused with the previously described Testicular Dysgenesis Syndrome-  . This syndrome is the result of variety of factors which are  in operational.  Many uphold the view that there is point mutations but environment has  an added role in the expression of the disease e.g. maternal toxins, maternal life style, dietary habits, lack of exercise . However, in continuation with point mutation paracrine  theory in cases of TDS is also contribute to nonproduction of sperms . This absence of local coordination between different growth factors and paracrine funaction eventauly lead to stoppge of spwrm function .

Therefore there is both abnormal functions of Leydig cells (which secrete intratesticular androgen) and abnormal secretions / synthesis of Sertoli cells . Sertoli cells are the PILLARS of a multi storied bldg and normally secrete  many known & unknown  products which pass on t nearby  semimeferous tubules to synchronize the production and some degree of maturation(acquision of functional competency of sperms)  spermatogenesis. But final maturation of sperms occurs at epididymis.

 

 

 

 

Type  2 Few points on oligoastheno zoospermia  (not azoospermia) : :  Sperms are present but are of poor quality:- The causes are 1) MAGI- Male Accessory Gland Infections of varying nature, 2)Acquired Testicular damage( sports injury-cricket ball injury in particular). ---A partial  damage-à therefore subnormal functioning of testis –

Sperm production can also be  interfered with- Life style factors, Obesity, Environmental  toxins, Varicocele,  systemic disease, Ageing, Immunological causes, one sided obstruction of ejaculatory duct (either vas or epididymis).

 

 

Type  3 Male Subfertility.  Male sexual Disorders:- Disorders of Erection, Or ejaculation.

Mostly psychological drugs, Psychotherapy, Sildenafil types of drugs may work.

\. Is there any seasonal variation of seminal quality?

 Age-adjusted analyses of seasonal variations in andrology patient semen parameters showed significant seasonal variation in the percentage rapid motile sperm and straight-line velocity, as well as the percent tail defects, percent immature sperm, and the percent tapered sperm. Such seasonal variations might prove to be clinically relevant and important when designing experimental protocols.

Clinical Examination:   tall, robust, less beard, scanty moustache- may be  a case of Klinefelter’s Syndrome. Age above> 50 yrs= poor sperm quality.

What is Kartageners syndrome (KS) Association of primary ciliary dyskinesia along with situs inversus is termed as Kartageners syndrome (KS). Though some  scientists insist that only when triad of 1) chronic sinusitis,  2) bronchiectasis  3)  situs inversus exist then and then only that person will be labeled as KS. Dextrocardia and dysosmia as well as a history of chronic bronchitis and sinusitis, the classic triad disorders Kartageners syndrome ( KS)

 

What is Young Syndrome ?

The association of frequent RTI, along with azoospermia is called Young Syndrome.  The azoospermia is “Obstructive in nature “ and is due to  inspissations of secretions in the epididymis.

What is Cystic Fibrosis  disease ?

It  is  a common autosomal recessive disorder more common in Northern part of Europe.  CFTR is important for maintenance of viscosity and fluidity of epithelial secretions. If there are mutations of CFTR gene than CBAVD-or sinusitis. Vas is often absent.

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. History of Male Partner.

Local infections, Trauma on testis, H/o Mumps, Kochs, Filariasis, Viral diseases, Polygamy, Local hygiene, . Testicular trauma, undescented testis, History of sexual dysfunction, Stress of modern society and food habits. Loss of libido and premature ejaculation.-warrant psychological support.  Drug Intake/ Life style. How he spend his life ??

 Degree of stress relaxation, sports,  enjoying holidays, any fear losing job, Occupational exposure to toxins, Alcohol, smoking, Cancer chemotherapy causes some damage to germ cells- e.g. cyclophospamide. What  is the total number of drugs currently he is consuming ?  More the number of drugs-à more probability of seminiferous tubule damage. There will be chromosomal brakes and abnormal of springs.

History of Male Partner :Sexual history:-

Any impotency, premature/ retrograde ejaculation

H/O Surgery :- Scrotal surgeryàhernia, Hydrocele, Brain surgery, Hernia repair, Retroperitoneal sympathectomy

History of Male Partner : Any Medical diseases:/Sytemic Diseases.-

 

If there is recurrent Respiratory tract Infections –then one should consider Cystic fibrosis gene mutations. In such cases vas will be congenitally absent  of  vas on either side also called CABV. There are two special symptoms associated with either azoospermia or OAT. These are Kartageners Syndrome e.g. ciliary defects and Young syndrome which mean the there is inspissations of testicular secretions at the level of epididymal level.        

 History of Male Partner(contd)

Central Nervous system Tumours—Thyroid diseases, Liver abnormalities are not uncommon accompaniment of poor quality of sperm. Similarly visual fields problem and headache will raise suspicion prolactin disorder. Hepatomegaly associated with Gynaecomastia points to alcoholic liver diseases or other disorders of steroid metabolism.

Following points have to be enquired e.g.,

1) Pubertal development:

3) Any history of anosmia? Cannot smell properly.

4) Sexual history- Change of libido, Erectile or ejaculatory disorders. Any psychiatric drug therapy?

 

 

 

Clinical Examination of Male Partner.

Gynaecomastia; Eunuchoid appearance, less body hairs, absence of male pattern body hairs, Small testis. Any hydrocele, hernia, epididymitis, any scar in scrotum/ inguinal region,  Per rectum palpable seminal vesicles and or enlarged prostate.

 

 

 

 

 

 

 

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Investigations of male partner (Contd)

A) Hepatitis serology, B) Viral Screen c) Ebsocrine : TSH, Free T4,  PRL  ,testosterone  D) BMI  E) Rpt semen analysis . If earlier repot suggest suboptimum then one should repeat preferably after 2 months i.e  Routine semen analysis,   F) Lab tets for   for systemic diseases,   G) . Sperm function tests, H) . Chromosomes. Gene testing,  I)  Venography is not done nowadays but scrotal sonography and imaging of seminal vesicles and Prostate should be done by TRUS(Trans Rectal Ultrasonography) . His  is warranted if  repeated routine tests  reveal poor seminal parameters.

 

 

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Treatment of Male Subfertility:--

Unlike females the defects in males are difficult to ameliorate. Many therefore  jump on to  IUI procedure . However the recognized methods of treatment (medical Treatment are A) Life style modifications, Hormones like gonadotrophins, Antioxidants. Presence of ROS I seminal fluid is being recognized fast /.

Role of  Antioxidants and vitamins in male subfertility?

Many doctors do prescribe 1)L- carnitine,2)  Astaxanthin,3)  Vitamin E, 4) Vitamin C,  5) Co-Q, 6) Zn, 7) Lycopene, 8) Selenium, 9) L-arginine, 10) Alpha- Calcidol, 11) Omega-3 Fatty acids, 12) DHA and 13) F. Acid 14) Glutathione  to promote fertilizing potential of ejaculated sperms.. It is understandable that    role of antioxidants in male subfertility is somewhat  effective as time and again has been notices that the quantum of ROS  in seminal fluid is high when seminal parameters are substandard.

What antioxidant in what dosage?

There are many questions which remain unanswered. A) What element B) combination of elements to Supplemt and at C) what dosage? D) How long? E) How do we select out of eight commonly recognized antioxidants which one is will help one particular person??Unfortunately, answer is not known to us. Admittedly many of us empirically supplement antioxidants. For instance, in cases say 10^th per centile motility, as a solo abnormality or say a case of combined with 15th per centile morphology-what antioxidant will be most suitable if no obvious cause is detected and couple is too young for IUI /ART?

 

What are the medical Treatment for OAT  ??

A)      :- Antioxidants, Vitamins, Life style changes, Timing of coitus, Treatment of systemic diseases(DM, Thyroid, Hypertension, Psychiatric disorders), Occasionally Inj testosterone ,better still inj. HCG 2000  i.u. at the dose of   weekly three time. But in that serum testosterone have to be measured 3 monthly. Some use Gonadotrophins  for development of small testis but it will be prudent to  combine HCG along with HMG as it is the hCG which stimulate Leydig cells to promote intratesticular production

Treatemnt  for zoospermia:-

One has to diagnose the kind of azoospermia. Is it Obstructive (FSH & LH are normal and possibly absence of Fructose in  semen)  or azoospermia is  due to NOA(nonobstructive azoospermia). In  cases of Obstructive azoospermia ans is surgical reconstruction of the blocked segment of vas/ Seminal vesicle. But question is will reconstructive operation will restore Patency  and functional sperms will be available at ejaculate? If not ICSI/TESE are the solutions., .

 

What is the “Technequies.of Sperm retrieval (Surgical Sperm Retrieval).”??

A) From Epididymis:- 1) by percutaneous route- called PESA: percutaneous epididymal sperm aspiration

2) MESA:_ Microscopic Epididymal Sperm Aspiration :- The aspirated material is later  processed by  density gradient centrifugation

B) From Testis:-TESE- 1)   Testicular Sperm Extraction, 2) TEFNA:- Testicular Fine needle Aspiration.

 

Treatment  of  Oligozoospermia.

 What is to be doe is sperm count (Density) is low ? :-  Better two reports from two different lab  at an gap of say 2-3 weeks and again 2 months apart to confirm the abnormality. Upto 15 millions –No treatement. If abnormal sperms are upto 86% NO WORRY, NO TRETMENT. By medical treatment 5-10 times increase in sperm count is possible. Abstinence  is often the cause of failure of IUI as more abstinence will  yield either dead sperms or aged  sperms .But if morphology is below 4% normal-> then better IVF/ICSI.

 

Brand names of different antioxidants

BRAND	Company	Co-q	l-Carnitine	Vit e	zinc	selenium	lycopene	Astaxanthin	Dose per day.
Fertisure-M	Spectra-Sun	50 mg.	-340mg.	-	5 mg.		2500mcg	8mg.
Carnisure-500	Elder	-	500mg.	-	-	-	-	-	2 tab TDS(3Gm)
CoQ Forte	Sanofi	120mg
Z-Y Forte	Indecheme 35/- per cap.	Co Q only-100	-	=
Supakem	Alkem-1 cap per day-12/-		Superoxide dismutase.
Paternia	Zudys Nutriva	30	440						bd

 

Qute	Yash	Co-Q	L-C	vit	Zn	sel	Lyco,Asta
Carnimed Plus
Xfert-mf	Akumentis.	yes					1 cap & 1 tab daily.

 

 

Types of antioxidants:-

a)          Ace antioxidant:- Astaxanthin

b)        Repairing antioxidant: Lycopene

c)           Bio-energetic Antioxidant: Co Q-10

d)        Nurturing  Antioxidant: L= Carnitine

e)         Immunomodulatory Antioxidant: Zn.

f)              Antioxidant

Ig Tg Forte (500mg.) 1 Cap BD: (Alchemist) Rs. 17/-, Colostrum Natural.

 

 

 

To determine the expression and enzymatic activity of glutathione peroxidase (GPX)-1, GPX-4, and glutathione reductase together with glutathione (GSH) concentrations in spermatozoa from fertile and infertile men.

Design

Prospective study.

Setting

University-affiliated private center.

Patient(s)

Fifty-four infertile men undergoing assisted reproduction techniques and 55 fertile sperm donors with pregnancies and newborns by artificial insemination.

Intervention(s)

None.

Main outcome measure(s)

Analysis of gene expression by fluorescent quantitative polymerase chain reaction and an analysis of enzymatic activity and GSH concentration by controlled biochemical reactions and spectrophotometry.

Result(s)

GPX-4 activity but not mRNA expression is directly related to sperm morphology (strict criteria) and is more compromised with a low percentage of normal sperm. These differences are also demonstrated when fertile and infertile men were compared. In addition, intracellular GSH concentrations are lower when sperm morphology is severely impaired, but no differences were found between fertile and infertile men.

Conclusion(s)

Intracellular sperm GSH system components GPX-4 and GSH are altered in infertile men, and these alterations seem to be linked to sperm morphology