Monday, 4 May 2020

Routine semen anysiss


What do we mean by semen collection errors??
Have you had any occasion when the concerned husband failed to procure fresh semen when trigger has been done and there is failure to comply with collection of seems at the time of IUI?? “Situational anejaculation”??
 Every media and is ready but there is collection problems in IUI?  Magnitude of the problem?? How big is the problem??
-       10 % of men are   unable   to give a semen  sample
-       Some  have never  masturbated
-       Some   are inhibited  in the clinic(unfamiliar situation) . 
-       Some   fail  on demand (DEMAND EJACULATION) .
-       Some are brought up at religious family and cant masturbate.
-       Quite often semen spills in collection room error and  few man are too anxious and mixes tap water to make the total volume identical to normal ejaculate vol of 2-5 ml.
-       Few men use saliva/ some lubricating agent to ease the masturbation and this can falsely decrease the count.
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Failure to procure   a sample can be very embarrassing and disheartening  for a man   and can produce long  delays in treatment/ cancellation of the cycle unless frozen sample is ready well ahead which is costly   . To avoid this problem always    ask whether a man can collect a sample when advising a semen test. If  he  reports difficulty in collecting semen instruct him to try collecting at home  using coitus   interrupts . Special  non  spermicidal condoms are  also available. Those  who are still unable to collect a sample will usually be  able to ejaculate when  stimulated with a vibrator .
Message on male subfertility :--1) It is  important  to remember  that semen   analysis is only a rough  predictor of fertility  2) So reassurance is very important  when the semen  is sub normal   because  the male  ego is very threatened by a poor  semen report 3) It is not uncommon to see  that  many pathology laboratories still quote  the old  norms  misleading  the doctor and making   the couple    unnecessarily nervous.4)  Many  men with  poor semen   parameters will still father   children while others  with seemingly normal   parameters will be infertile. 5) The duration    of infertility   should be considered in addition to the semen   analyses. If the duration is short   then even with a low   count  the chances of pregnancy   are good  while if the   duration of infertility is long then even  with a normal analysis  the chances of pregnancy   are poor.  Time acts  as a filter  sorting  out the fertile from the sub fertile regardless of the semen parameters  Hence   young  couples  who have  been trying only for  a short time should not rush into advanced reproductive techniques.
Azoospermia is present in 1% of all men   and 10-15% infertile  men. To  establish diagnosis of azoospermia : Semen    specimen is  centrifuged   at high   speed  and pellet is examined    at magnification of 400 X.
Note :   Absence of  sperms  should be documented on two  occasions   to diagnose   azoospermia .
Azoospermia can be 

Obstructive  : Blockage   anywhere   in the ductal system  from efferent ductules  to ejaculatory     ducts  as a consequence of :
Severe   infection
Iatrogenic   injury  during  scrotal   or inguinal surgery 
Congenital   absence  of vas.
Intrauterine Insemination
Non  obstructive : It  may be due to :
·     Intrinsic testicular disease
·     Endocrinopathies or other   conditions that suppress spermatogenesis
Note : Men  with non obstructive azoospermia should have a careful examination of centrifuged   sample as in one third of   these men  a very low sperm production  insufficient  to drive epididymal transport   and entry to ejaculate is present . These  sperms can be recovered  by TESE   for ICSI. If the case the case under discussion is a confirmed case of OLIGO,& urosurgron has examined and excluded anatomical diseases -endocrine evaluation, including PRL, Cortisol, DHEAS-O4,TSH, Renal, Metabolic profiles and karyotyping has been done and H/O drug intake and life style have been duly analyzed then there are several options depending on the age of female partner, duration of marriage etc. If female partner is >35 yrs and duration-of marriage is > 10-14 yrs, I shall prefer for ICSI straightway.-because from social point of view upbringing of child usually takes about long 15 yrs active life on the mothers side. But this ICSI is applicable if count is persistently below< 10 million. I understand many will opt for IUI with oral antioxidants,/ pooling of several samples-->IUI, but as because the female partner is aged I personally is biased for ICSI/traditional IVF-ET. The other option particularly for relatively young couple, say wife is somewhere between 30-32 yrs-then possibly the oral antioxidants , modified life style of husband , avoiding illicit drugs may be attempted. In such settings IUI has a definite place provided the count is 5-15 million with over 30% motility and at least 608 % morphology  normal. But when husband comes to know that his count is low he, willfully refrain from coitus in the IUI cycle so that a good no. of sperms will be available for IUI procedure. This should be strongly discouraged. Result of IUI will be low.. I must admit, I have no personal experience of treating male partner --with HCG/hMG .not to speak of CC.My mentor, Prof. B N Chakrovorty used to prescribe Methyl Testosterone  Tab during the period 1065-1085 when I was associated with him and worked under his supervision. But , If count is below< 5 million ,I routine perform Karyotyping and exclude Fragile X syndrome/ CF gene mutation if couple can afford. before I proceed for ART procedures(be it ICSI/IVF-ET). I have no experience in prescribing on Tamoxifene, /Inj testosterone- but now I am impressed with results of antioxidants particularly those containing Vit E, C B12 selenium.

What are the Top of Form
·         What are the Physical properties of semen ?? A) opacity:--  If semen looks absolutely transparent (like water) then there is reason to believe that count is really too low. But after due liquefaction if it (liq sample) is reasonably turbid then it implies a fairly good amount of sperms must be present to make the liq. sample( crude sample) turbid in naked eye/ or at least opaque. .Otherwise it would have been as clear as water provided there is absence of pus cells in light microscopy. This observation may give a clue about oligozoospermia or azoospermia
·          
·         B) Viscosity:  A highly viscous sample  may falsely cause  OLIGOZOSPERMIA (low density) semen-A) if semen is viscous- a primary disease of prostate/ seminal vesicle-has to be considered due to lack of hyaluronidase enzyme. However in a viscous ample too actual  count will be apparently low if the technician is not dedicated & do not know how to assess the count in a viscous semen .  . Prostate secrets PAP, Vesiculase, Hyaluronidase enzymes etc to liquefy the coagulum formed at upper vagina soon after ejaculation which coagulum sticks to the upper vagina loosely.,Threby even if female partner leaves bed for toilet or dress change  most of the ejaculated semen remain stuck at upper vagina  entrapped in coagulum.. The semen coagulum forming after natural ejaculation -on the ectoCx/ upper vagina- after deposition in the female genital tract starts liquefying after about 10-20 minutes and then though most of the sperms at the periphery of coagumlum are dead or devoid of motility die to acid pH. We should remember that sperm cells are the most fragile cells of body and Oocytes and anterior horn cells of spinal cord arte the largest cells of the body and none of last two cant regenerate once damaged..


 Low density if associated with low volume semen implies collection errors, frequent coitus/ diseases of accessory glands ( to be confirmed by clinical exam/ TRUS(transrectal Ultra sonography) / Clinical evaluation by Urologist).

What else to order in oligozoospermia?? Presence of blood/urine & Bilirubin may be ordered if persistently report come as oligozoospermia  .Incomplete ejaculation occurring due ,out of apprehension in uncommon settings--- may be rare cause of oligozoospermia  so also unilat ejaculatutory  duct obstruction (semen of pH will be fall below 7). .
How useful is clinical examination?? Therefore it is mandatory to clinically examine the male partner before embarking on costly tests- karyotyping, endocrine evaluation, TRUS etc/ Colour Doppler not to speak of antioxidant/ Antibiotic Ry.
Relevance of PCT in 2020??  I personally still insist on POST COITAL TESTS in low density sperm count cases( 7 motile sperms/HPF) is excellent and defies the Lab report of oligozoospermia.. Sometimes things become easy .
Pus cells may not be pus cells : No unnecessary antibiotics please:-Incidentally pus cells and immature sperms are not usually differentiated with appropriate stain (peroxidase stain but not by H E stain) neither agglutination of sperms are duly tested. Regards-Dr. S K Pal.
 For kind attention of junior members only:-There several books available on male infertility formulating tr. plans for male subfertility .. I quote herewith which may be of help to U. A) Male subfertility . -A clinical guide-Ed, Anne M Jwequier, Cambridge University Press(www.cambidge.org) B) Male Infertility- Contemporary Clinical Approaches. Andrology, ART& Antioxidants-SPRINGER, Ed. Sijo J. Parekttil , Ashok Agarwal. C) Infertility in the Male- 4th Ed. Ed Larry I Lipshultz, Cambridge University Press(www.cambidge.org); D) Male reproductive Dysfunction Author- S C Basu, Jaypee) Additionally the Biennial Review of Infertility Vol 3, 2013, (Springer Publisher) -the very first chapter is dedicated on role of antioxidants in male subfertility..Dr Pal.


SPERM MOTILITY
 Sperm motility  is assessed as a percentage  of total   sperm   population  exhibiting any motion. Factors   which   effect sperm  motility are :
Patients   age, health  status, and  length of  time  last ejaculated
Patients    exposure   to outside  influences  such   as  excessive  heat or toxins
Length of time  and adequacy of handling from  collection to analysis.
Forward  progression
Whereas  sperm  motility represents  the   quantitative parameter  of sperm  movement   expressed  as a  percentage   sperm progression represents the  quality   of sperm   movement   expressed in a subjective scale. 
Forward progression is graded on a  scale of 0 to 4
0:  No   motion
1:  Motion  with no forward progression
2 : Erratic   movement with slow  forward  progression
3: moderate   speed with relatively straight   forward  motion
4: Rapid   forward progression

The motility of each sperm is further   graded a to d
Poor sperm motility   may be due to :
Testicular dysfunction
Anti sperm   antibody 
Genital   tract  infection
Partial  obstruction of ejaculatory  duct
Varicocele
Prolonged    abstinence
Immotile  cilia  syndrome



Intrauterine  Insemination
Total   progressive  motility Percentage  of sperms exhibiting purposeful forward motion . The probability  of conception increases with increasing motility  upto 60%
 Motility assessment can be done in two ways
1.A wet  preparation
2.Computer   aided sperm  analysis.
Six   uL of undiluted well  shaken semen  is put on a  clean slide and covered  with a cover slip. This   gives   a standard  depth of observation. Examination  should begin after   one minute  when flow has stopped.
Motile sperms are defined as any sperm with a moving  flagellum whether or not the sperm is progressive.
Number of fields to be examined: At least 5  randomly selected fields are sampled
Number of sperms  to be  counted : 200 spermatozoa  are counted for motility and classified. The  counting procedure   is repeated  in the second chamber.
Difference in  counts between two chambers : if   the percentage  of difference  between  the two  values is :
10%  or lesser  the mean   of the two  values  is taken
More    than 10%  a third reading is taken  and an average  of the three is taken.
CASA
The CASA  instrument   digitalizes the electrical  signals that result from repeated video  scans of a field  of sperm The sperm cell is recognized because  of its  optical  contrast  with the background. CASA  provides  numbers   that quantitative  the vigor and pattern of movement   on a per  sperm  basis.
When  no motile sperms  are observed a sperm  viability test  should be done to differentiate  viable non motile  sperms from dead     sperms  as it is important to identify living  non motile  sperms  for ICSI
Sperm  morphology
Normal   sperm  morphology has been related to fertilizing potential  of sperm. This may be because :
1.Abnormal   sperms inability   to deliver  genetic material  to cytoplasm   of the egg.
2.Sperms are   more likely  to have   diminished motility     due to :
3.Hydrodynamic inefficiency of head  shape
4.Abnormalities in  tail structure   which prevent normal   motion
5.Deficiency in energy production which is  necessary for movement
Do not bind to the zona    as well as normal   sperms.
Sperm  morphology  usually is assessed from seminal  smears  that are prepared  at the time of  semen evaluation   and subsequently   stained . It can be  assessed in several   ways the most  common classification system  being  the third edition WHO    standard and the Kruger  strict  criterion .
BASIS: Spermatozoa  with visible anatomical  defects are not functional cells  and there   are many clinical   reports   that associate  defective sperm  shapes  with infertility   . There is considerable  variation      in visual  morphology assessment . According to the WHO k standards the cut off for normal   semen forms  is 30%   . This was  decreased to 14%
Whereas  sperm  concentration and  progressive motility  have value  in discriminating fertile  and infertile  men  strict  sperm morphology   has  emerged  as the one most discriminating value.
Strict sperm morphology represents  the best  predictor  of sperm function    is a widely accepted   indication for fertilization by ICSI.
The   likelihood of male infertility   was increased approximately 4 fold when strict  normal   sperm morphology   was less  than 9% . The   9%    threshold value has a sensitivity of 43%  and specificity of  815  for identifying infertile men. When   sperm   morphology is assessed  according to strict normal   standard in vitro fertilization  efficiency  correlated   with percentage of  normal   sperms  during IVF.
Method   of preparation
The WHO   method  requires either  a wet slide preparation   or a fixed stained slide. A 10 to 20  ul drop  of semen  is prepared on a slide. After    placing   a cover slip   over  the  specimen   morphology may be  assessed  Alternatively the specimen may be fixed   with equal  volume  of fixative and Methylene  blue prior to fixing  it on the slide. At least   two smears   can be  made from fresh  semen sample.
Effect of  method  of preparation on results.  The method of preparation has an effect on results. Sperm   dimensions  are different on seminal  smears  in comparison   with wet smear   and staining  methods can affect cell classification . The  greatest accuracy   and precision    on morphometric    measurement   are obtained when sperms    are washed   and  resuspended  to standard  concentration before  slide preparation
If sperm   concentration is > 20  x10 ml 5 ul semen  is used
If concentration is < 20 x10 ml 10- 20  ul semen is   used.
They are  fixed and stored for  staining
Normal  morphology
For  a sperm to be considered normal   the sperm  head  neck  midpiece and tails should be normal   and single.
Method : Examination  is done in oil immersion at 100x  field  magnification . An ocular  micrometer is essential  for thorough    morphological examination . Defects are  expressed per 100 sperms  for that  region.
Number of sperms to be assessed : 200  sperms are assessed . Only  recognizable  spermatozoa  with tails  are considered   in the count. Immature cells   upto the stage of round spermatids are not counted . 100 consecutive sperms are counted  in two randomly selected areas
If  percentage difference  between the two is :
·     Less  than 15% then the mean of the two is recorded as percentage  morphology
·     More than 15% a third  reading is taken  and average  of all  three is taken.
Protocol for evaluation : Criterion for further evaluation is a single   head and tail. Sperms with  more than  one head or tail are scored as duplicate  sperms and are not evaluated further . so  also those without head classified   as headless or pinhead sperms  . Sperms  with any tail  abnormality are classified as  amorphous tail regardless of head  or midpiece morphology . The rationale for primacy of tail morphology      is that such sperms  can be considered dysfunctional because   absent or severely abnormal   flagellar activity will   result  in failure   of sperm  transport   to site  of fertilization    or penetration   of oocyte. If sperm  tails  are normal   in size  and shape   the head of  the sperm  is considered. Midpiece morphology  is assessed  last only  if head and tail  are normal . To be  classified as normal the sperm  must be normal in all three – head tail and midpiece.
There  may be sperms  with more   than one abnormality
Teratospermic index-Average number of sperm defects  per sperm
1.WHO   criterion for sperm morphology
WHO  criterion for assessing sperm  morphology includes   the following :
Head  Defects

·     Oval , smooth  head normal
Round  Pyriform , pin , double , and amorphous head is abnormal Head Defects
The  length of the head  should be 4.0-5.0 um and width 2.5-3.5 um. The length to width ration should be 1.50 to 1.75
There   should be a well  defined pale acorsomal  region comprising 40-70 %  of the head  area
The sperm head  appears pale blue in the Acrosomal region and dark blue  around
·      

Tail Defects

·     Single , unbroken  straight without kinks or coils
·     A  normal  semen  analysis   should  contain   30%    normal   sperms  using  WHO criterion
·     Krugers  strict criterion
·     In order   to perform  the Kruger  strict  criterion  sperm  morphology  is evaluated by placing  5 ul of liquefied semen  on a slide making a thin smear and air  drying at room temperature   . The slide is then   fixed  and stained    Kruger criteria  for assessing normal  forms  include  the following

Midpiece Defects
Midpiece should be slender   less than 1 um in width and one  and a half times  in length  of head and axially attached  to it . Midpiece
·     Straight slightly  thicker  than the  tail  

Cytoplasmic droplets should be less than half the size of the  normal  head and are stained green  Papanicolaou stain is used.
The   midpiece is stained red.
Tail
The tail should be uniform straight thinner than midpiece uncoiled and  approximately   45 um long attached  symmetrically
The tail is either blue or red
This classification  requires that all sperms which are not clearly normal are  considered abnormal   . The   forms are considered normal If > 14%  are normal .
Kruger  strict   criterion   for morphology
Classification
Normal - > 14%
 Borderline – 4 to 14%
Abnormal - < 4 % 
Abnormal :
The   defect could be in the head  midpiece or tail
Tail  defects : The defect seen are :
Short
Multiple
Hairpin
Broken  tails
Bent   tails
Tails   of irregular   width
Coiled  tails
Combination  of these
A high  number   of coiled  tails  indicate  that the sperms   have been subjects  to hypo  osmotic  stress. It may  also  be due to sperm  ageing . If > 20%    it must be   noted. Sperms   with any tail  abnormality  are classified as amorphous tail regardless of head or midpiece  morphology 
Head defects : These   are :
Large   
Small   Tapered
Round
 Amorphous heads
Vacuolated heads
Head  with small   acorsomal    area
Double  heads
Combination  of these
Pin head  or micro head sperm are not counted
Neck  and midpiece  defects
Bent   neck 
Asymmetrical    insertion    of the midpiece  into head
Thick and irregular midpiece
Abnormal   thin midpiece  
Combination of these

Cytoplasmic droplets : Cytoplasmic  droplets are more   than one third the area   of normal   head sperm. They     are usually  located   in the midpiece.
Method  of Measurement
A transparent overlay is drawn using a stage micrometer  to determine the size of the boxes. The overlay is placed  on the screen so that the base of the   sperm  head is aligned with the bottom of the overlay.
Normal : If   the length  and width lie between the boxes the classification is normal   
Large :  If the length and width  lie outside the outer box the classification is   large.
Small :  If the length lies within the inner box it is small
Tapered : if  the length lies outside  the outer    box or between the two  boxes and the width inside the inner  box it is  tapered
Amorphous : If  the outline of the sperm  head  is irregular   or asymmetrical  or both the classification is amorphous  regardless of sperm   dimension . If the outline is smooth   and symmetrical   but the length lies  between  the boxes  and width  outside  the outer   box it is termed  amorphous
Kruger strict  method  has been  used to  predict a  patient’s   fertility   to show   the most   consistent  prediction  of fertilization and    in vitro  following insemination. This method of assessing normal   sperm morphology  because  of  its precise non  subjective nature  establishes  a threshold value  below which   abnormal   morphology  becomes contributing  factor   to infertility .
Cellular  elements other   than  spermatozoa
The ejaculate contains cells other than spermatozoa  referred to as round cells. These  include   germinal  line     cells  sloughed from seminiferous tubules  epithelial  cells from genitourinary tract  prostate cells spermatogenic    cells and  leukocytes . A normal  ejaculate should not contain more   than 1x10 round cells

  Printed :IUI Tips.
Good semen preparation should have 6-8 million/ml of prepared semen and 99% motility.
Double IUI only when perifollicular PSV (Peak Systolic Velocity):- > 20-25 cm/sec.
Good success of IUI depends on good USGà Color Doppler/Power Doppler/ 3D power Doppler of follicles and endometrial blood flow.
CO2 incubator must, :IUI in the second cycle of post-drilling.
Prevention of OHSS.
If at the time of IUI the serum E2 is > 5000 pigmy/ml then possibility of IUIà immediately treat with IV albumin & start cabergolin 0.5 mg for 8 days.




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