Azoospermia, defined as the total absence of spermatozoa in the ejaculate, requires a reliable laboratory diagnosis through repeated semen analyses with centrifugation to exclude cryptospermia, followed by appropriate sperm retrieval techniques (TESA, TESE, or micro-TESE) based on whether the condition is obstructive or non-obstructive, with the choice of retrieval method depending on testicular volume, FSH levels, and histopathological findings.
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From Absence to Opportunity: The Science of AzoospermiaAdded:
faculty members and all the delegates.
Thank you for joining. This is Sahiti on behalf of Shield Connect welcome you all for today's webinar from absence to opportunity the science of Azus PMIA organized by IFS Tamil Nadu chapter. So let us start the webinar with Sarasati Bandhana.
lamp lighting.
It's my privilege to introduce Dr. Ajenta Bupati Ma. Mom is the secretary of IFSTN chapter from 2026 to 2028. Mom has 15 years of experience in reproductive medicine, trained in reproductive medicine in UK and mom has membership in so many societies. I welcome you ma'am and I hand the session to you. Thank you Saiti for the kind introduction. On behalf of Indian society Tamil Nadu chapter, I warmly welcome all our esteemed speakers and participants.
Today's webinars on aospermia brings together valuable insights and practical approaches to complex area of male infertility. I'm confident this session will be highly relevant for our clinical practice. Thank you all for joining us.
Let's begin. I'm uh it's my pleasure to introduce Dr. Arti the coordinator for the program. Can I have Dr. Arti slide please?
Dr. Arti is a managing director lead consultant Manu Hospital Kamaturur.
She's active member of IFS and all the other societies. She's center in charge of Semar Kuatu. She's a present executive committee of our team. She's a past joint secretary of IFS Tamiladu chapter. She's vice president of Cox.
She is also recipient of young talent award visa 2022 and Dachara award is 2024. Uh welcome Arti and please I request you to kindly take over the session.
>> Thank you. Thank you Ajenta. Good evening everyone. Uh actually it's my pleasure. uh Ajenta has given me the opportunity to be the coordinator for the first CME which we are conducting on behalf of this uh new tenure where Ajenta has taken over as the secretary.
So uh I I I selected uh good topics for the day. This being the first uh webinar uh we have four vibrant speakers. Um I would like to invite the first speaker Dr. Saruna Dvi.
She's a senior clinical embryologist, health and care professions council UK registered clinical scientist. She's got more than 20 years of clinical practice.
committee member of ACE India and visiting faculty of Aspire and Mysore University and she's got affiliations with national and international level hospitals um especially international with care for UK sims clinic republic of Ireland. Her areas of interest are advanced embryion sperm selection and previous IVF failures along with the clinical audits and quality control in IVF. I would like to invite um suna Dvi to speak on one second from zero to strategy interpreting ausperia and securing sperm. Welcome Dr. Sarunvi.
>> Yeah. Uh good evening everyone. Thank you so much Dr. Arti for the kind introduction and um congratulations and all the best to team IFS Tamilad chapter. Best wishes to you for your future academic endeavors and um so I'll share my slides.
Do you see my screen?
>> Yes, ma'am.
>> Okay. Is it moving?
>> Ma'am, please make it as full screen, ma'am.
>> Yeah, sure.
Is it moving?
>> Yes, ma'am.
>> Okay, without any further delay.
Um, so today's topic of my presentation is um confirmation and interpretation of aospermia and if any surgical retrieval of the sperm for aospermic men plant.
How do we process and secure the sperm?
It's purely a laboratory perspective I'm going to talk about. there is no much clinical um correlation except in a few points would come.
So semon analysis is the key um investigation of male infertility we all know. So as per world health organization auspermia is defined as the total absence of spermatzova in the given ejaculate that's all it's not implying any specific underlying cause anything so no sperm in the sample is called eospermia it's affecting high number of men in across the world around 10 million men from 2013 report must be more so you know the impact now so it is affecting the treatment outcomes etc. So a proper reliable laboratory diagnosis of aospermia is very important in an ERT setup. So as an overview I'm going to touch the evaluation and interpretation of the no sperm situations happening in the laboratory. If surgical retrieval like testicular sample retrievals are planned, how we process the sample to make sure it's available for ixie and we can cryopreserve the sample and just a slide about future development just one or two biomarkers we are having. So and then I would just summarize the whole uh presentation. So in a normal day we have the sample um container given to the man and instructions given receive the sample keep it for liqueifaction at 37°C in the laboratory to have a uniform spread of the sperm. Do the microscopic and microscopic examination give the report as per the WH referral values from the sixth edition from 2021. So there is a um a given normal range limit for all the parameters. So in case if you are checking the sample on a counting chamber, you have loaded the sample and you're seeing no sperm present in the ejaculate that will appear like this. You may not be seeing any visible sperm on the entire area of the slide or the counting chamber across the grid or outside the grid and you may see only the seinal fluid with its contents like debris and cells may be present. So now what are you going to do in the lab? So how do we evaluate?
Evaluation is just not there. So we may have to go back to pre-examination um details from the patient as well as after that you may have to really decide what you're going to do after the microscopic evaluation in the as a first step. So pre-examination um details must be collected from the patient. For example, his history did he have any previous reports of aospermia any zero count or there were situations he couldn't collect any ejaculate like apermia does he have any fever is it just leading to transient aospermia whatever sometimes the patients come with frequent ejaculation with a short period of abstinence so that may also give u there may not be enough um stores in the epidermis to give samples so there may be no sperm or poor sperm in the initial um sample did he spill any sample particularly the initial sperm rich fraction that is a question because later we'll be totally composed by the seminal vesicular fluid so initial fraction so this much of information we have to collect from the patient and come back to your sample now during the microscopic examination you might have observed the appearance and the color and the and the homogeneity of the sample everything so see whether there is less opaque compared to the normal semen sample which is gray opolescent and homogeneous. So the opacity may give you some information and check the volume now it is 1.4 ml as per the sixth edition otherwise whatever I quoted in this um presentation was just referred from previous papers so it was just having all the 1.5 there is no much difference it is 1.4 4 to 1.7. So just have an idea about what was the volume make it accurate and pH see whether it is acidic or alkaline that is going to give more information for clinical interpretation to your clinical team.
Okay for example on a broad scale you may be dividing it into obstructive non obstructive or hypo hypo whatever. So normal volume normal pH no sperm in the initial sample may be connected to NOA low volume acidic ejaculate less than 7 or 6.8 8 PH may be connected to obstructive visospermia. HH will have hypospermia, less volume etc. So this is very important you make sure that you make a document of all these information. So coming to the microscopic examination. Is there anything missing? Your junior or and technician or some practitioner is checking the samples. Is there an incomplete liqueifaction? Because if somebody's in a hurry to make sure uh to not make sure that it's completely liquefied or it is taking longer to liqueify, you may be checking the portion where it's completely liquefied but sperm is present in a non-queified portion. So that could be a a reason or do you have any sperm aglutinates aglutination or aggregation? So aggregation is sperm attached to the sperm cells like uh sorry cells present in the seinal fluid or sperm to sperm association is called aglutination either head to head tail to tail or the other way around.
So just check is there any sperm aglutination present somewhere else other than your portion like whatever fraction you have used for checking.
What about the competency of the practitioner? Um we have a standard protocols in the laboratory for someone to do the semon analysis independently.
still how many aosopermic samples they have checked in the and during their course of uh training. So uh could they differentiate between artifacts and the sperm everything to be queried at that point in time and replication of a wet preparation second sample after complete mixing and liqueifaction should be checked. Cross verification means two people must check another senior should check the sample to make sure the initial neat or raw sample is having no sperm present in the 10 microL whatever we have checked what happens next post examination the standard practice in the laboratory is to plet the whole sample on high speed so that you don't miss out any sample and it also excludes cryptospermia we know what is cryptospermia initial need sample will have no sperm in the pellet you may find low number of sperm that is called cryptos sperm. Yeah. So we make sure it's not crypto and poor oligo. Uh so just make sure it's on the high speed and the time is maintained. So 300 sorry 3,000g it is more or less it's 4,000 to 7,000 rpm depending on the size of the rotor. Um and sometimes we may just wait for 5 minutes finish the spin and check the sample give 15 minutes so that you are not missing out anything and that is confirmed this nose bumper. So confirmation happens at least with two consecutive semen analysis not just with a single sample. So he has to repeat the semen analysis with the uh prescribed um abstinence period again so that we can just give enough information appropriate information to the clinician. So in 2010 who edition just adopted the sediment the word so pellet of pelleting of the sample is very very important. Do we have any alternative methods other than centrification in the laboratory to check the entire sample? Yes, we have first one low semen dilution that is uh with the fixative as 1 is to2 ratio but this takes it's like laborious you may have to use large volume counting chambers make a thorough check or multiple chambers as needed to check multiple samples still it's not going to check the entire sample. So next one is the fllororesence microscopy.
Their their sperm is diluted with the fixitative and this fllororesence will be labeled onto a sperm nuclei. So the entire sample can be checked in the microscopy and find out whether any sperm is present. There are limitations the cost as well as less accuracy. So most common routinely method used method in the laboratory I would say is the centrification of the sample.
So when it comes to centrification of the sample and checking it again. So I practice like you take the whole pellet leave it on a round dish like 60 mm dish take it to the Xy microscope so that you have the entire area checked entire sample checked you don't miss out anything coming to the fructose testing is it necessary some of the milk line fructose is fructose testing is necessary when it's there is an obstruction that is what is going to indicate us because it's a marker of seminal vesicles function but some of them would say some of the authors are saying like fructose not at all required still we need to know What is fctosis say? It could be qualitative where you add resource in all kind of chemical boil it for 45 minutes it color turns into red from the colorless. So there is a positive note that there's sperm present that may be present. If it is not turning into red no otherwise you have to go on a quantitative phototric method where the same is mixed and then checked under spectraph photoometer. So you know the range of fructose present.
If it is less than 13 mg per deciliter, I'm sure it is going to be no fructose present in the sample. So you interpret now as a confirmed aospermia. How do you do that? Because at least you need to have two samples. First analysis in my practice in my team we don't say it is aospermia. We always say no sperm found and to repeat the sample because there are a lot of there is a biological variability in the sample as well. In two different intervals when they give the sample there may be variation only the second sample we confirm the findings of the previous analysis and interpret that as aospermia even if they have got an aospermia result from elsewhere I don't know whether it's a reliable lab or accredited so I would always repeat at least once so that we have two samples to confirm that now every information is passed on to the clinician proper communication is there within the team and the clinician is going to uh make a treatment plan for the couple. So she may be or he may be planning for a surgical retrieval of sperm so that we know whether any sperm is present from the testicular sample.
There are different methods of sperm retrieval available as you all know uh testicular epidmal um aspiration or extraction from the testice or microsurgical testicular sperm extraction microy. So how this is planned as well as when this is planned is entirely depending on multiple parameters totally upon clinical decision I would say. So it depends on the hormones and etc your clinical valid evaluation as well as how the patients mindset is all about. Do they want to know about the sperm earlier? Are they ready for a backup plan like a donor sperm plan in case if there is no sperm?
Do you think it's an obstruction? Then you may plan it on the egg collection day or you may have to do it early. So either it is diagnostic or clinical the decision is from the clinician. But the job from the laboratory of processing the sample is the same with any of the samples only microtissa takes longer otherwise it's the same. So when they give the aspiration for example we see the sample like this under the microscope. So aspiration may have the fluid but may not be having any tissues.
Sometimes they will have you will have small short tubule uh content tubular content in that. So you may be seeing different type of cells red blood cells other cells and you may be seeing the sperm they may be motile um slow progressive or immortile anything is there. So you have to document all this information how many sperm you see on high power field as well as what is the rate of motility and if you want to add on anything the presence of zetto cells etc that gives enormous information to the clinical team. When it comes to testicular samples like proper tubules are given to you like tissues there are different methods of processing those testicular samples could be mechanical or enzyatic micrfluidics or magnetic levitation but mechanical methods are the most commonly used as well as easiest the easiest method what we follow in the laboratory I'll just show you um the picture this is very interesting from estas and our own Alexis reported in 2012 there's a nice picture. So you see the dish where this tissues are given to you in the buffer from the testus from the extraction etc. So this is the tissue focused max um on a mag magnified picture. So these are the tubules what we are seeing. So what we use is the tubicle in syringes 1 ml sized with the needles and I generally bend the needle so that you have an angle to touch the tubule and completely press the tubules both the sides so that the contents of the tubules are released into the fluid what you have the buffer.
So keep repeating it's like a spaghetti.
You just rotate as as like a spaghetti and keep pressing so that every area of the tubulus is releasing its own content and you are taking the whole sample under the microscope that is the highest magnification you're going to take it in the X microscope and see again the number of sperm present and hypograph the motility the pattern etc. Everything needs to be documented. You need to document the appearance at and the and the texture of the tubules also. They are sometimes dark. They are not uh sometimes they when you touch them they are dry and you don't see any sperm inside and whenever they are smooth you are expecting some kind of sperm present inside. So is there any spermatitis present? Is it elongated spermatzova?
Everything to be documented from the embryologist that is going to be quite useful to the team. When it comes to microti samples I would just advise like it takes longer to finish the procedure for clinician the surgeon as well as the embryologist. It's highly uh strainous, laborious for us. It the OT needs to be well equipped. You have to have all the equipments for the microscope for the surgeon as well as the microscope for us because we need to dedicate somebody for 2 hours minimum. You get 25 to 50 samples given from the surgeon and we have to just merate every single sample and then just go and check under the microscope collect sperm present sperm absent and pull all the samples and make sure everything is fine for the um um injection IC or whatever. So you can plan the microy on the previous day one of the centers where we were doing microy in and out. Um we may have one or two microy sample exes every single day out of the whole number of exes. We used to schedule that the previous day so that we know we have enough we have no sperm or we have sperm. We can leave it on the room temperature. Next day you can wash it and use it for the ixie. So how do you prepare the sperm for ixie?
That is very important means processing and washing of the sperm. So the method of preparation is based on the gross estimate of the sperm density and motility. So is it less number more number? How many are motile? Everything is involved. There are two different types most commonly used in the lab. One is simple washing. Add buffer spin it for 5 minutes take the entire sample load it for and go ahead. So where there you have a worry about you may be losing the sperm from different washing methods you better go with simple washing. Other method is gradient centrification. So you can use two different discontinuous cent gradients or a single gradient or mini gradient like you reduce the volume of the gradients. um where you have red blood cells, debris from the cell, cellular debris, animotile sperm, everything is present. You want to separate them from the sample so that your ixie becomes easier and our voice will be lesser. Go for gradient centrifugation dish preparation in Ixie just one slide.
You may have to make larger droplets like legs add the sperm into it. The final pellets you have P droplets other hepisplain buffer media um droplets sperm is added go across the edges so that easy to find the high motile sperm go to the PVP immobilize them take it for injection so in my practice I always do the fishing first you collect enough number of sperm or even more number of sperm um ready in the PVP droplet load the oite so that the micromanipulation time is less and the exposure for oides is very minimal in case if you have only immortile sperm present in your testicular samples you don't see motility even after leaving it for a couple of hours what you do there are different types of sperm selection on Ixie uh to have select the viable sperm to be injected for the first one is hypoasmotic swelling test where you add the sperm solution in the buffer to a lower concentrated solution for example if you're taking a sperm buffer adding to one is to one water sterile water that becomes half the concentration add it you add to the add the sperm to the lower um hypoasmotic solution you see the sperm curling and you have to select the sperm and inject.
Next one is sperm tail flexibility test.
This can be done you can use the micro injection paper touch them and feel or you give laser shots to see the movement of the sperm and select it. Last one is use of modality stimulants which is uh quite commonly used widely used across the centers and these ones example penttoxillin and theophilain what we have used so far there are so many phosphodiest trace inhibitors which are acting as motility enhancers. The simple mechanism of them is they will increase the cyclic adenosine monophosphate cmp that is to give energy to initiate the movement or speed up the motility when they are exposed to that solution for 20 to 30 minutes. It's a peak 20 to 30 minutes they will gain the motility after 30 40 minutes they will slow down with the motility and go back to immortile status. So you have to be covering that window collect all the sperm. So usable for XC efficacy has been reported and we have seen quite a good amount of results from the microtrTc used with pentoxfillin and theophilain and um long-term effects as like any other add-on for the sperm or any any add-ons we use in the laboratory to be studied.
So do can we do cryopreservation of the testicular samples? Can we thaw them and use it for exi in the future? That is an additional question. So how do you secure sperm? That is the that is the answer for the title what been given to me. So where do we cryopreserve the sperm? Either we will cryopreserve the sperm intentionally if it's a diagnostic da or desi or if you have exiden and you have any number of sperm still available as surplus it can be frozen secured for the future for the future cycles. For any patient who are having good amount of sperm, you think like they will survive after freezing and thawing, I would certainly suggest a freezing.
Particularly for NOA men because they may need more cycles to achieve the success. Protocol is the one used for normal ejaculated sperm. You have to mix with uh freezing media. Add them drop by drop fashion because the sperm should not be um able to cope up with the shock if you're adding them completely. Mix them properly. exposed to liquidation vapor and then do a flash freeze like this the picture on the right. So there are different methods of cryop preservation as well. One is like when you have very small number single digit numbers you are having in the sample means you can take an empty zona um and then inject the sperm into it secure it and freeze the entire zone of pelvic for future purpose. Second one is whole tubil cryopreservation. Once the sperm presence is confirmed from the testicular samples no more masseration but save them all as tubules in the wilds later when the ex is scheduled you thaw them as the tubule process them by then wash them and use it. This is also been practiced from different um IBF clinics. So thawing is very similar to a normal ejaculate thawing. Thaw the sperm whatever device we have got it in in the room temperature. Wash it for 5 minutes with the buffer to remove the cryoprotectants. Do the exec because you have frozen and thought we are expecting a lower level of motility or very poor motility zero motility expected from these kind of samples. Then again you have to think about sperm motility enhances to gain the motility posting to use it for exe.
In case um there is a scenario that there is no sperm present in the testicular samples when you are checking under the microscope initially as well as after pelleting from the testice what do you do obviously like centrification check the pellet and these tissues um are placed in bo solution and sent for testtopathology examination the solution is very toxic so we generally don't keep it inside the laboratory complex it's always outside and that's how it's useful for the hystopathology examination and they will give you the report and the clinician has to interpret with the Johnson score the possibility of the patient to have some sperm in the future it can be interpreted by then so coming to the future development I have just one slide just to hint um within this 20 minutes I have to finish you know so that seinal plasma proteomics that appear to be having high potential to identify some biomarkers. So many of the proteins in the seminal plasma are expressed in the testus as well as in the epigenous and they are highly associated to fertility. So some of the proteins may be useful um they can serve as biomarkers non-invasively to give a discrimination between non-obstructive esospermia from obstructive. So if you have some information like this, I'm sure it is going to be quite easier and useful to make a decision on the treatment plan for the couple and plan the cycles very successfully.
To summarize my presentation, a reliable laboratory evaluation to confirm aospermia is very very important. Clear instructions verbally and written to be given to the patients at the time of collection and you have to get the feedback from the patient if necessary.
We have to have sound protocols for the laboratory techniques to have reduced error as well as high precision for evaluation and reporting of the sperm quality must be present. So there should be a communication and clinical interpretation of seinal parameters and proper counseling um with the patients as well as planning for treatment to be enhanced and the choice of the sperm preparation and Ixie as well as the methods for career preservation um must be uh like followed properly as per the instructions from the SOPs. Um finally the laboratory must have a quality control quality check on entire aspect every aspect in the laboratory to make sure um we have not missed out anything in this manner like for example if we have an aospermic example we are not missing out anything and we are on the right direction we're planning the cycles and then give the pregnancy and the live birth to the treat um to the couples who are just coming to us for the treatment from from the ASUS permit.
So thank you so much. These are my references.
Thank you very much.
>> Thank you.
>> Thank you. Thank you very much. Uh Sarati.
Um that was a very clear description about diagnosis, interpretation and sperm selection techniques as well as stressing us the importance of quality check at the end of your uh talk. Um so far we don't have any um questions in the chat box but I would like to ask you one question in what type of patients do you recommend micrfluidics for your exy patients >> patients it's not about yeah right >> so yeah where we have high amount of sperm DNA fragmentation >> found um there is a big debate on that DNA fragmentation in most of the times we have something around 50%age. So if it is exceeding 25%age, we may just give the option of micrfluidics. It's more natural. It avoids centrification. So that we may think like the sperm collected from the micrfluidic chamber is going to have high DNA integrity and less DNA fragmentation. So the patients with IDFI will have micrfluidic selection.
>> Okay. Thank you.
So um we'll be moving on to the next session. Thank you. Thank you so much Sadi. Please uh stay for our next presentations as well. If you have any questions or chat, I'll ask you in between.
>> Thank you so much.
>> Thank you. So now moving on to the case based discussions. Um more or less I think it's going to be like a dialogue between uh two speakers our own Dr. Anit Kumar and Dr. Mad Priya. Uh welcome Dr. Anit and Dr. Madu. So Dr. Anit is a director promise fertility center Chennai and consultant in Sri Kumaran Hospital West Tambberam. His areas of interest are infertility and reproductive endocrinology, high-risisk obstetics and male infertility. He is um executive committee member of ATNRC and IFS Tamil Nadu and he is backed the youth icon fertility award from ISAR in 2023 and he has authored five chapters in medical reference textbooks. Dr. Dr. Mad Priya a very good friend of mine uh she's a clinical director and senior fertility physician Nova Aia fertility MRC Nagar Chennai and she is uh back >> yeah tell me an >> no sorry ma'am >> okay so uh Dr. Madu has bagged uh awards for her papers and posters in Oxy, RCG, ACG, YSR and she has also won the youth icon award in 2023 and best paper award in COGS 2024. She has published in BJOG and UCP and her special interests are biological hair for poor ovarian or sperm reserve patients and encoertility.
So over to you Anif and Madu to discuss about cases.
>> Thank you madam. So >> writing >> we have planned it such that I'll be presenting a case on nonabitetas permia >> and madu madam will be presenting a case on abs to adjust.
>> Oh that's a two case presentations.
Good. Good. Sorry I think I thought it as a dialogue. Okay go ahead please.
>> Yes ma'am. Yes madam.
Okay. So uh so my case uh is on uh maturation arrest. Uh so we'll be talking about diagnostic pitfalls or how to manage the case. Uh so going directly to the case presentation. Um uh so we hired a male patient around 30 years. Uh they both doctors. Uh the male was on a slightly obese uh range of DMA forum 34 and when they came with me they had um uh salmon report of has been done twice and confirmed. Um uh so other past history is uh they there's no medical and surgical histories. Uh there are no other relative history like anosmia or fat test chemotherapy therapy. Noism was negative. The female partner was around 31 years old. Uh she was a physician.
She had regular cycles and no gynecological complaints are present to the female partner. Uh so on examination um uh the main was well built around BMS 34. Second section are well developed.
Pification was normal. Testers were well designed well normal sized around 16 to 17 ml each. Uh every was normal batch was present val was seen and parallel examination was not done but transcal ultrasound was done to confirm. uh so normal testicular volume with aspermia so this is like bit confusing so if the testice volume is bit small so we could make the conclusion that uh probably it could be nonstructive also so moving on to an investigation part so these are the investigations done again I did an assess to confirm theia FSH LH was in the normal also was a normal around 420 product in 25 we could consider as a normal or high normal TSH was normal. Keratyping done was also normal. Micro deletion was also done which also showed no dilution.
Ultrasound showed normal testicular with no adequacy. A transc ultrasound was done. Um so in this uh also it showed a mild right with a poorly visualized right semicles.
similar is equal to not seen or probably unilateral obstruction was the picture that initially was came and that was the working diagnosis. So based on that um so these are the based on this like a normal testicular volume was normal was normal and probably a right unateral obstruction. So we were actually I was more actually consing the patient this could be probably an obstructive uh and uh okay uh so we could go for stimulation uh so the couple opted to go for a trial tisser before going for naive stimulation because and both were doctors so it was easy for me to consult and both were quite accepting for the fact that they did want to go for a trial ta uh so bilateral so so patient is portion for a trial ta bilateral trial t local anesthesia with such sedation also So uh so around 6 to9 quadrants was sampled in each quadrant of tesa for the testers. Uh so interoperative uh tracing and analysis showed that the lot of abundant vacated cells were present. Uh that a lot of immature cells was also noted but there was no mature spermata was seen. So the sperm so the tissa was actually a failure. there's no sperm retrieved and this TSA sample was then sent to an estopology showed sperm certoite arrest with certly cells present light cells present there's no tubular fiber and Johnson score was around four to five in this case so this is a Johnson score so the score basically tells from no semiferous tubles to complete satogenesis this patient's Johnson scores around four to five was what is reported and based on this Johnson Johnson score you could probably say what would be a a sperm retrieval rate.
Uh if the patient was again posted for a microisa uh so with the with the uh joint score of 4 to 5 the sperm retrieval rates could be around 10 to 15 percentage what realistically concept for the patient. So uh uh so this is uh a maturation of uh sperm uh thing. So you could see that uh the round germ cells go through various places like primary spermicide, secondary spermicide and then move on to a mature head, neck and tail formation. So this patient had an arrest at primary to secondary sperm site. So what is so failure of jamson to complete the programmed repiated sequence within the semiferous epidium as maturation arrest. Uh so so because of this you can see lot of accumulated arrested type of cells could also be seen. Uh so it could be a primary maturation error a secondary maturation or late maturation arrest. So um depending upon what stage of maturation arrest is in or it could be also classified as a uniform maturation arrest and non-uniform maturation arrest where identical uniform maturation arrest is identical arrest is through seen throughout all the tubules. This is very consistent and the probability is probably low and non-uniform maturation arrest is there are variable arrest stages as seen across tubules and and in these cooperation the probability is little bit higher since we are sampling in multiple st location and then this could be a uniform or mutation error is difficult to say. So what are the reasons maturation errors could happen?
Most commonly it could be genetic aberration. There's a lot of genes that have been implicated uh for maturation rest or it could be because of a hormone changes like gonotropin deficiency calments uh or some uh uh uh uh this thing or it could be environmental like uh just one second one second.
Is my screen visible? Sorry. Sorry for the distance.
>> Yes. Yes. Go ahead and it's visible.
>> Okay. Sorry. Sorry. Sorry. Uh so it could be very uh sometimes it could be toxic or acquired. It could be because of chemotherapy, radiotherapy. Sometimes obesity itself one of the reasons implicated but we couldn't be very sure.
Sometimes it will be idiopathic also. Um so how do you treat mutilation errors?
Uh so there are some evidence that putting the men on high dose of recominant epicets and LH combination could improve your chance of sperm retrieval or it could also increase the chance of sperm and ejaculate. Uh there are various studies there are lot very less number of studies done on maturation errors hardly a handful of good quality studies. uh so you could expect a marginal improvement of sperm in about 10 to 20% of cases across various studies. Um so what did I do for this patient? So I did consult them that uh okay let us go on a recombinant FSH and recombinant LH for two per uh I mean twice weekly. So we council that around 10 to 20% chance that you might get exactly sperm if there is no disperate around around 20 to 25% is what we did.
So on mid month 3 months we did analysis uh it showed a persistent perpia. So serum app was elevated which was saying that the patient is complained to the treatment.
So it was decided to go for a full 6 months course and after 6 months also there was no improvement. At this point of time the couple were not willing to wait any more time and they did want to go for an IVF stimulation with simultaneous micro this couple. Uh so the female partner had pretty normal features of AMS 3 and uh 30 I mean she 31 years old. So we did an antagonist protocol and 16 M2 was done. Microisa was done by a neurologist. Uh so with an operative microscope and with adequate uh magnification.
Uh so uh we trying to see any dilated sensor but there is no dilated seen through it. There was an extensive micro done over 3 to four hours was spent searching for tubules. But the outcome was even after this thing there was no spermatosa was seen bilaterally. Again the sample was done sent for pathology all the samples and both samples uh with proper examination found that still mutation error was found. Uh so uh even with the microissa with early maturation error from some sites there micro the tissome could be only up to 20 to 30%age depending upon what the you need to consider that patient patiently. So obesity in this patient could cosmonic be a reason. Uh obesity has lot of factors why spermance is affected because of armation cordal hypothermia oxidative stress and adopine dirulation.
So in this patient what happened was they didn't want to go for a donorite this couple. So they did wanted to go verify all the sites that was um um available because um at this point they found very difficult to make the decision. Uh so you could do a relication it could be a good bridge therapy rather than cons directly for uh donas at that point of time. uh so because us postification is pretty good around 80 to 80 85% do survive clinical pregnancy rates are pretty normal with fix because we brought adequate number of usage around 16 the pregnancy will be pretty high also another important of doing is cyclop because making them putting them on spite for a donor formation is very difficult uh they could have adequate time also to decide what they want to do. All these things are reason that uh it is always constant before pick up itself. Uh should better to not put the couple on the spot and make them decide then and there.
Um so uh what will be the future plan for this couple?
Uh so at this point of time uh it is very difficult. Uh we are in the discussing phase. Uh so I've suggested them to do a whole exam sequence. uh in the whole of some sequence we could identify some sperms that could possibly uh say which uh what are the recent information could be find there are some experimental treatment these all experimental treatment that has been in research none has been properly used for clinical practice yet uh so there was an high is treatment given for male patient only one case single case evidence was done so there was sperm one some sperm improvement was found this is done in sation where rounds per sperm injection done and live birth rate was got and then future perome stem cell transplantation was done in animal mode only these are pre-clinical studies um so what are the learning points so normal testicular volume and normal gonotropic hormone profile do not exclude nonobstructive testicular what is going to give us so in this patient we had unilateral transal abnormality uh so but uh just because patient doesn't mean that it could be abstia John score of five. Uh so we need to consult them properly about what is the chance that sperm material rate could be in microiza. So empirical therapy even with good dose of recom may not give um improvement. So that but that is a good treatment option. So you need to at the end of the day you need to cons them properly give them realistic numbers what is going to be the perman rate. So which will help you the patient make informed decision properly. So microisa is gold standard uh when permanives superior to just a plain TSA. Uh soification if PL is not microisa is a good option. It needs to be given to the patient and it is quite popular now and in this patient what we're going to plan is in doing a whole exam sequence in future which could help us in identifying what could be the reason for unexplained maturation arrest in the future. These are my references. Thank you.
>> Thank you Anit. That was a brilliant presentation and thanks a lot for sharing your experience with us. Uh please stay with us uh till uh Madu finishes her presentation.
>> Madu are you there?
>> Yes.
>> Good afternoon man and all. Uh can I request uh Sahiti Priya to actually go ahead with the PPT slides for my sake.
Thank you so much.
So good afternoon one and all. Thank you so much for the kind introduction Dr. Artima. And at the outset thank you if Samaladu team for giving me an opportunity to talk about obstructive aospermia in this webinar.
So as we see in this slide the average sperm concentration million per ml this is just a reference value right from 1973 to till date where we see that the sperm quantity keeps decreasing.
This also tells us that the male infertility is on the rise and the male fertility is declining. Next slide please.
So when it comes to the bottom end and it is zero and it is aospermia on the paper which says about the semen analysis is aospermia considered the end of male infertility 1% of general population and about 10% of people with male infertility do have aospermia as the diagnosis and obstructive AOSpermia which contributes to about 40% cases of aospermia mostly is correctable or a person is able to get a biological plausible baby from his own gametes in nearly 100%.
Next slide please. So when we think if there is light at the end of tunnel in case of obstructive aospermia we all know that more than 90% and nearly 100% of people with obstructive aospermia which are properly diagnosed without an associated non-obstructive aospermic condition have a full-blown potential to have good sperm retrieval recovery. But yet this obstructive aospia is a frequently misdiagnosed and mismanaged condition that prevents the man from having his own biological broken. Next slide please.
Now there is an important step here to differentiate between abstractive and non-obstructive. And yes we have direct factors and indirect factors. directly the size of the testice, the volume of the testice, the volume of the semen, the sperm parameters, the hormones, the FSH and the LH and directly by doing a Pisa or TSA check and if necessary a testicular sperm extraction or a microt if it is a obstructive aospermia.
Identifying obstructive aospermia is the first step using the indirect assessments followed by differentially diagnosing it from the non-obstructive aospermia where there is no sperm production or very local focal sperm production inside the testice and to choose the type of surgical sperm retrieval technique that has to be done.
strategize the treatment policy and to know in some cases if surgery could be an alternative option rather than an IVF or ART and all these needs nuances in counseling the couple because it not only depends upon his factor but also on the female factor including her age, the ovarian reserves, the tubal factors and their age factors and the number of years that they are married, how many kids that they would like to have. Next slide please.
So as we see obstruction as a cause of aospermia it could either be the obstruction in the vaso epidmal region or it could be at the vasal area was difference is obstructed either because of congenital absence or acquired because of either vasectomy or because of infection post infectious or ejaculatory duct obstruction which is post infectious most of the time. Next slide please.
So whether it's a congenital absence or an infection or post vasectomy or because of the idiopathic reasons that we have an aospermia which is not considered a non-obstructive cause. Next slide please. We do have a stepwise evaluation.
What is the first step? As we all know there are two times that a semen analysis has to be done to make sure that it is a diagnosis of aospermia.
Secondly, a clinical examination like sometimes absence of a vast difference unilateral or bilateral or the presence of associated non-restrictive aospermia if the testice is going to be smaller in volume or shrunken or associated varicos. These all could be identified using the clinical examination followed by hormone check mainly the golod droplets and then imaging mainly the transferral ultrasound and if necessary genetic testing to rule out chromosome abnormalities.
Next slide please.
As we have different types of obstructive aospermia, there are case-based scenarios which we can discuss to identify how a man can present with obstructive aospermia and how do we derive at the conclusion and how do we go ahead with the management.
So there are four cases lined up where case one is about this male who is 30 plus years. He's been having 3 years of infertility. normal libido normal sexual uh function and no abnormalities in the erections. Simmon analysis done twice during the fertility assessment showed aospermia. So volume has been 6 ml which is low and the pH has been acidic of the semen and the semen analysis also showed absence of fructose. Next slide please.
So here the low volume of the semen together with the acidic pH and the absence of fructose points towards obstruction in the distal area which could either be commonly an ejaculatory duct obstruction post infection or sometimes it could be a vasal obstruction in the distal part. Now use of semen analysis done twice at least one week apart with a clinical examination which is done to rule out the congenital absence of difference and an imaging which is helpful to identify the volume of the testice and the blood flow will help in pinpointing that it is an ejaculatory duct obstruction. Next slide please.
So if it is going to be a congenital bilateral absence of vast difference then it's going to be a sperm retrieval along with ixie that's the treatment of choice. In case of ejaculatory duct obstruction we have a trans urethral resection of the ejaculatory duct as another option too. But whether the surgical repair is considered or an art procedure is considered again is based on various other factors depending on the condition depending on his marital status number of years that he's married to the female factors like the age the ovarian reserve and the tubal factor and also on cost factors.
Next slide please.
In the case two, he's a man 28 years who is diagnosed to have aospermia.
He has got a past history of epidemorgitis. In our setting, the most common infection that we think about is a tuberculosis. Of course, there are bacterial reasons which are lined up next to that. And now his clinical examination shows thickened epidmus and his other parameters like the transctal ultrasound and his hormones are normal. Next slide please. So here the epidermal architis induced obstructive aospermia is an obstruction at the level where the testice and the epidmus meets. So this is identified using a semen analysis done twice a week apart at least showing aospermia which confirms the diagnosis of aospermia. A clinical examination showing thickened epidmus with a past history supporting the same with an imaging showing the epidmal thickening can help us identify this to be an obstructive aospermia indirectly.
Use of hard modes where the FSH LH done is normal guides this into the diagnosis.
Next step this will be evaluation whether a surgery is needed or an art is required at this point. A microsurgical repair needs to be concentrated where the patency go is claimed to be about 50%. The pregnancy rate is found to be a maximum of 30%. This does not include the live birth rate. Next slide please.
So considering these rather than a vasoepidostomy a surgical sperm retrieval with Ixie would be a better option whenever there is a obstructive aospermia due to infection at the epidma or junction.
Coming to the case three where we have a 40-year-old male. Here both the quantity and the quality matters. He has undergone vasectomy 10 years ago and now a new female partner they want to have fertility. Next slide please.
Post vasectomy the nuances depends on the number of years after the vasectomy when the vaso vasal anesmosis is to be tried the sight of the vasectomy it also depends on the female factors as we have already seen so now whether it's going to be a reversal or an IVF is a question here next slide please in case the female factor is normal. Age of the female is less than 35. The tubal factors are good. Both tubes are patent and healthy and her ovarian reserve is good as well. The number of children that they are trying to have is more than one.
Cost factor is considerably low then a vasectomy reversal is a first step to be tried.
But because vasectomy reversal always doesn't give a guarantee in case they have to go ahead with a vasectomy and then they do not have a proper sperm production and then if there is an associated non-obstructive aospermia which has not been identified then they're going to go ahead with an art after surgical sperm retrieval which is going to cost them doubly. So identifying obstructive aospermia making sure that there is no associated non-obstructive aospermia becomes very very important. Next slide please.
So in case a surgical sperm retrieval technique and an ixie is identifiably the chance or the choice that the couple intend to it's a good choice especially in people after vasectomy more than 10 years that they've had the vasectomy for or in case of foster conception is needed because the age of the female is on the higher side and her amh or the oarant reserve is decreasing or they prefer only to have a single child and in case there is a sexual dysfunction that is persisting. So even after correction of the vasectomy uh even after the surgical repair the possibility of pregnancy doesn't happen.
Same is the case when the ovarian reserve is poor or the associated tubal factor is abnormal surgical sperm retrieval of the sperms with ixie becomes the treatment of choice. Next slide please.
As we go ahead with the last case, we have this man with aospia where everything is normal. Normal testicular size examination is normal. Vast difference is present. The hormones have suggested that the gut dropins are normal. Even a carotyping is done to identify the cause and it is found to be normal. Next slide please. This is an idiopathic obstructive aospermia. And here a semen analysis done twice one week apart identifying an obstru identifying an aospermia and no clinical examination imaging or hormones or genetic testing suggesting the reason for obstruction. We consider this idiopathic and the treatment of choice as well as an investigation for why an obstructive vospermia exists can be a surgical sperm retrieval. It can start right from tisa upperccutaneous epidmal sperm aspiration if that doesn't help microepidal sperm aspiration or a teasa testicular sperm aspiration or a testicular sperm extraction. Finally, if nothing out of these surgical sperm retrieval works, then a microtz that is microtesticular sperm extraction is the treatment of choice here.
Next step please.
What if obstructive aospermia is diagnosed? Tissa is done. No sperms are obtained. As we saw the ladder has to go up from teaser. You can shift tease testicular sperm extraction. If that also doesn't help then a microt where a complete opening up of the testice to identify the best of the seminiferous tubules and then taking the uh sperms from those good semin but it is also very important to know if there are no sperms even after a microtz and TZ which constitutes about 1 to 2% of cases of obstructive aospermia then it's important to re-evaluate the diagnosis because most of the time it's a misdiagnosis of only an obstructive aospermia and misdiagnosing the associated nonobstructive aospermia and considering that there is no non-obstructive aospermia existent is the reason for a flip in the diagnosis. Other reason which could lead to no sperm despite an accurate diagnosis of obstructive aospermia without any associated decrease in the sperm production is due to complete epidmal fibrosis.
So in cases next slide please in cases of obstructive aospermia which is properly diagnosed which is ruled out of the associated non-obstructive aospermia where the hormones suggest that it is obstructive aospermia and the sperm production is good where the female factor is all fine including her age the ovarian reserve the tubal factor and the number of children that they want to have is less.
Yes, there is light at the end of the tunnel and there is nearly 100% chance for obtaining his own sperms though not 100%age of pregnancy rate. Thank you one and all. If there are any questions we can take it over before we go ahead with the next session. Thank you so much for the opportunity.
>> Thank you Madu. That was a brilliant presentation with four different cases.
Uh we have with us um um Dr. Kartiken he's a microsurgical andologist and neurologist from Apollo Chennai. So uh can we have some discussion with sir about these cases?
>> Yeah.
>> Sir are you?
>> Yeah. Good evening. Yes sir.
>> Just one minute. Okay.
>> Yes.
Meanwhile, I'd like to introduce Dr. Karthikin. Uh he's a microsurgical androgist and neurologist at Apollo main hospitals, Greens Road, Apollo Fertility, Chennai and Andromed Anaagar, Chennai. He has done clinical fellowship and observer uh in andrology from great mentors like Dr. Vinit Malhotra and Dr. Ranjit Raaswami from Dio's Mental Health Center and Miller School of Medicine, University of Miami, USA. He's a fellow of European Committee of Sexual Medicine, European Society of Sexual Medicine as well and um he's uh he's authored chapters in practical urology textbook and he's editor of andology session of urological society of India.
He's got um so many uh awards specifically he's the best outgoing student in urology and as well uh in MBBS graduate from Jupiter Pondicherry he's a best outgoing student presently he's the editor men's health society of India member of editorial committee Indian journal of urology and co- member of Indian school of urology sir >> yes ma'am good evening and thank you for this opportunity I thank Ajenta mam and the for this wonderful the concept itself is very good that from zero to opportunity and I thank both Dr. Anit and Dr. Madubria madam for putting out those those uh cases so well. So what I was uh thinking is I already have the presentation ready and uh this contains some of the information which has to be discussed. So can I start the like I can complete the presentation and whatever is pending can be take up.
>> Sure sir please go ahead.
>> Okay.
Yeah, I think the slides are visible.
>> Yes sir. Yes sir, it is.
>> Okay. So both Dr. Anit and Dr. Madup madam they showed lot of like so many varieties of cases and how do we go about managing them. So in the initial two three slides I think around 2 three minutes it will take to just brush up like how do we as andologists evaluate isospermia so that then the treatment can be discussed later. So as we all know complete absence of sperms Dr. Sargonomad also told about the cryptospermia. So we all know that when a sample is given the first important thing is to spin and check for sperms.
So for somebody who is starting their practice only aospermia from CASA or some from some other regular lab may not be enough. The sample has to go to a fertility unit screened by an embryologist after centrifugation and then only we can declare it as. So this is a very important point and as we have been discussing throughout there is a non-obstructive and objective uses for this schematic diagram gives us an idea what is the basic difference between these two. So in objective there is homogeneous uniform sperm production where in non-obstructive it is patchy or focal spermogenesis as told by Dr. Madubria madam also. So when we are doing a surgical sperm retrieval whatever treatment the diagnosis whether it is non-obstructive or obstructive is very important because starting from the medical treatment till the type of surgical sperm retrieval depends upon what category we are discussing. So the causes can be hormonal imbalance, genetic abnormalities like line filter and Y chromosome micro deletion any which is still not fixed or it is fixed like arropexia has been done varicosil can be one of the causes any exposure to toxins chemotherapy radiation if that history is available. So these are in like generally the causes for non-obstructive espermia for obstructive already discussed by Dr. Madu it can be induced and it can be like congenital.
So it can be a congenital bilateral absin difference or it can be something like an infection or a duct obstruction or it can be postsurgical. So these are the causes.
So diagnosis simmon analysis as I just mentioned and detailed covered by the first speaker clinical exam I will be covering hormones and ancillary tests we all know just brush through. So a similar case couple married for 5 years aospermia 2.5 m fructose positive pH alkine this is a standard semon analysis looking like a non-obstructive uses permia so learning point is as I just mentioned and everybody has already mentioned the two simmon analysis your gap period is very important I have put three months because sometimes what happens is the sperms may come out in some like after some time the sperms may come and it can be very episodic or like there can be some times where the sperms Bump keeps coming out. So if there is a time available we can keep doing this analysis during the treatment. However for per say diagnosia we have to check.
So again Dr. Madu has already told this.
So whenever there is a acidic and the volume is low probably we are looking at obstructive esospermia. One important point to be noted here is if it is large volume say 10 ml 20 ml and the pH is acidic it can be uh urine instead of semen and uh the case which Dr. Madu told was like it was showing normal erections. So if there is erectile dysfunction there is large volume acidic semen or whatever then ask the patient whether the sample was correct. So as andologists whenever we take history for asospermy we still ask whether it was comfortable for you. Was the sample adequately collected? Uh is this the first time? Do you know how to collect a sample? These are additional information which we take on clinical examination.
Androgenization we all check testicular volume specifically if a pder or chrometer is available 15 to 25 ml is normal less than 10 ml we can think about non-obstructive esopermia and more than 20 25 ml can be taken as obstructive esopermia. We also should look for V difference on both the sides.
This is a clinical diagnosis. Even in the case presented actually we had done a trust. If the bilateral V is palpable and there is no epidmal fullness then probably your imaging is not probably necessary. So the clinical diagnosis CBD is always a clinical diagnosis. Whenever we have a doubt we always do a transone.
So look for epidemal tenderness which can be a marker of infection inflammation or epidemal fullness which can indicate a block. Similarly varicosil in standing position to look for what is the grade of the varicosil.
Could it be the cause for nonobstructive espermia? Varicosil and nonobstructive espermia is always a dilemma. We don't want to go into it today but then varicosil may not be the direct cause but varicoslectomy is certainly one of the important treatment options to be considered especially when the microcy is negative. We also look for scar of the previous surgery like a hernia hydroil etc which may lead to a block in the sperm passage. So again continuing the same patient uh borderline testicular size both vas palpable no epidemal fullness 2.5 female fructose positive all these things indicate that there is no obstructive here it is looks like non-obstructive we will do the hormones FSH LH testo so we all know the pathogenesis and like the HPG axis so on physical exam if the testicular size is low suggests hypoenism and noa but if it is normal probably OA may be a pro possibility.
Similarly, V is usually present in NOA very rarely like the VS is like absent in NOA and semon volume usually normal in NOA. It can be low in OA. FSH is usually normal in obstructive esoperia.
In non-obstructive it may be FSH is normal or high again testosterone usually normal in obstructive. In non-obstructive it can be normal or low and there are specific genetic tests for each thing. If it is a congenital like CBD then it is cystic fibrosis gene and for NOA it is carotyping YCMD. So up to this information is very important because okay up to this information is very important because we need to again come to this picture because we need to see whether we are on this side or that side. That is how we then go for the treatment.
Again the microal obstruction was already uh discussed by Dr. Madu. We have to understand that diagnosing microal obstruction is very difficult.
The block can be anywhere from distal to proximal. This is the proximal most obstruction. The only thing which is more proximal to this is the retest obstruction. Both these things we don't have any imaging to diagnose this. But on examination if there is epidemal fullness which is persistent even after ejaculation if the epidemal fullness persists then probably we are looking at this reason also and we can look in for a VA as one of the options otherwise it is not possible to diagnose this particular thing on either MRI or transcraculation it is a very even though it's a good diagnosis to have it is not very common because we have to have diabetes nerve related problems or very low tes Testosterone then only we are looking at retrograde ejaculation some retro surgery has already happened then we look at retrograde otherwise routinely it is not a usual diagnosis so whenever the semen volume is less than 1 ml we are looking at retrograde or we are looking at obstruction or a difficult sample collection so when we look at the next step we see the testicular volume semen volume FSH and if the FSH is low testosterone is low it goes into hypo hypo And if FSH is high no chromophane use then it is testicular failure. So the only treatment is sperm retrieval.
So at the end of this we have nonobstruct permia where there is a deficient hormone which can be low testosterone that is hypo hypopicure or genetic defects or varicosin. So these are the three main possibilities.
Genetics we all do carping y chromosome.
I will come to the advanced test later.
So the purpose of doing the AF is if it is A or B then practically the chances of getting sperm is less we may even avoid a microcy if it is C then there is maximum chance of sperm retrieval. This statement should not be misunderstood telling that if there is asc 50 to 70% sperms will be available out of Y chromosome. If this is only positive then only you get a chance to get sperms otherwise in other as of A and B there are no chances of getting sperm. And the second thing important to know is this is because we can do a PGT if we get sperms and good embryos we can do PGT to avoid the vertical transmission.
So in this patient again the genetics were normal everything is okay. So what next? So as I mentioned if the genetic is favorable we can go for sperm retrieval in XC. Again I will talk about surgical single stage sperm retrieval in the end. So we have to know this point very clearly that we can do a epidmal sperm aspiration or a testicular sperm aspiration. Nowadays misa is out of use because we either by simple needle aspiration itself we get sperms. Why do we have to go for a large microsurgical procedure when Pa itself can subside remain suffice and testicular sperm is the source especially non-obstructive whereas epidemal sperm is mainly the source in obstructive and good prognostic non-obstructive. So when we post a case when we are looking at the treatment plan if the FSH is high if the testice is small then we don't do P there we have to in fact do a TA or microtc if the test is normal CBD good palpable epidmus then P is the treatment so the difference between TISA and like a microt is in microtc like in an obstructive the sperm production is uniform so wherever you hit you are going to get sperm whereas in non-objective you hit the blank areas, maybe you're not going to get sperms. That is where a microcy comes in handy where we identify the probable area of sperm production under the operating microscope at 25x magnification. So this is a basic difference why a microt will work when a tissa will not work. So many people ask if it's a damaging procedure. We go by anatomical planes. It does not damage the latex cell or the testicular architecture. Therefore, it is a good procedure and the complications are not less. It means not more when it is done regularly in the center. But the requirements are it requires a dedicated over time of at least 3 hours. As Dr. Sunvi told the embryologist should be ready to spend 2 three hours for this case. It should not be on a day where there are 10 neck pickups already lined up and there should be a good quality operating microscope with at least 25x magnification. Of course, some skills and patience are very important.
So this case like went to some other place a tissa was done showed no spermoggenesis and the couple wants to proceed for further treatment. This is something very similar to the case presented by Dr. Anit. So when we like compare that patient with this patient of say going in for say microtc the only thing which you have to understand here is Dr. Anik presented a case where the testicular volume was normal and the FSH was normal. So that picture can be either obstruction or it actually otherwise also fits into a maturation arrest where this spermtogenesis is actually there but the maturation is not happening that is why the hormones are normal the testice is normal and it is mostly genetic. So in these situations we actually don't find lot of difference between a tissa and microt as I mentioned the focus of sperm production could have been there and that is why a microcy was done in that patient also. So similarly this patient also when we have a tissa negative non-obstructive esospermia how do we proceed as Dr. Anit mentioned donor sperm is certainly an option. Adoption is also an option. We have gonadotrophins which was used in that case and stem cells in advanced sperm retrieval. So these are the options in front of us. So when it is ta negative the first option is actually advanced surgical sperm retrieval and not gonadotropins especially when the FSH is high and we are seeing that this patient is going in for more of testicular damage and testicular failure. So it is many people says we have a probe also what we have it in the hand is more important than what we are going to get.
So a patient who is scheduled for a microtc we should not waste time by giving monotropins and waiting for 3 to 6 months. So we don't know whether in this period sperm is available and maybe after 6 months the sperms may become zero also. So we have to always do a microtc a standard microtc before declaring that yes now also it is negative we want to go for any further treatment rather than after doing ta v we will give injections then we will do microtc that argument is not always right.
So this case if it is the tissa was done somewhere and shows no germ cells on hp.
So this is like more worse like than the maturation error. This is satis cell only.
So couple was skin to proceed for further treatment. In this case if there are no germ cells on a t- cell what do we do again the treatment is microt. So now we have to understand this slide very carefully. So if the hystopathology shows maturation errors then what does it mean and if it is showing only settle result what does it mean? So before going to that we should understand this point. Testicular hisytologology is not to be finalized only based on tissa report because we have sampled only few spots. A standard microt is required to identify focus of spermogenesis and diagnosis that is to be made on multiple factors. It is not one thing. Similarly, when you do a hystopath, we can have either a complete absence of gem cell which is set to cell only. A maturation arrest where there is a production but it is not maturing into a mature sperm.
Hypospermitoogenesis where yes there are few of mature sperms but it is not widespread across the testes and normal spermogenesis. So complete absence of cettoil and early maturation arrest the treatment is very difficult. We don't have much treatment available at this up to that level but late maturation arrest hypospermogenesis we can find out some additional methods like gonadotropin stem cell these things may help from late maturation arrest onwards from but for the early maturation arrest or somewhere already the patient has a client filter complete client filter a set of a a set of b these patients are not candidates for any treatment somebody who is otherwise idiopathy there is late maturation arrest onwards on a standard microtc Then these are the patients we may try pre-operative optimization later. So when we prepare a couple for treating NOA we will do a couple discussion like Dr. Anit showed very beautifully how we do a couple discussion we take female part parameters into consideration and the new thing which we are also seeing in the last one and a half years is many people now come and say we don't want donor sperm we want to do all the options available. So we have to now discuss do you want to go for a donor sperm mix straight away or you want to freeze the wides and then proceed and what is the role for medical optimization that is the next thing to be discussed. So at this point we can also apply the aotic criteria. So we all know about this I'm not going to the details but this category is the one which our patients are routinely fitting into the elevated FSH and the reduced or normal total testosterone. If there is a low sperm contuspermia probably this is one of the important groups where nowadays they are considering recominant injections. The other two things already it is an indication to add a gonotropin especially if it is hypo hypo injections will certainly work in 2 three and four is it going to be useful? We are like looking at evidence and personal experience to see how much and how far these injections will work.
Medical optimization before microt we have these questions forward when how how long what are the end points and why very important this first slide before second microtc highlight because as I mentioned if somebody has only done a teaser the treatment is not optimization the treatment is microtc if the microtc has failed then comes medical optimization so before microtc after understanding the hystopathology there is probably no role for preop optimization in cell only or early maturation arrest. How it is not oral medical therapy, we have very less evidence to tell that chlomophen and anosol may help whereas recominant certainly are having a role in these patients. The duration can be minimum of 6 months because we need at least two spermogenesic cycles to at least prepare the milu inside the testice to start the sperm production. If we are seeing some case like late maturation etc. we really don't know whether there is sperm production also. So we have to give or plan this treatment for 6 to 15 months or even 18 months. Then only probably we are going to make a meaningful difference. But uh eventually we always know like how much how much time to wait and when to go for the procedure. This is a gentle balance for each patient. It will differ. The end point is the improvement in hormones and finding sperms in the semen. If we find sperms in the semen there ends the matter. But if we are still having only aospermia then we need to see based on the female partner age the male's testicular size the hormone levels duration of married life everything put together we can decide when do we want to go in for the next microt why we have to do optimization is because we if we don't do anything we are going to get the same result again so we usually look for medical optimization before going for the second microt so the next thing is consider optimization before microcyc only in this as I already mentioned after a standard microt when no sperms have been identified based on hormones and female factors favorable genetics and hystopathology showing at least late maturation arrest not in just a poster status or when the female factor is unfavorable.
So when next microt depends upon it can be from 3 months it can go up to 9 months and varicosil repair if there are good findings like a big testice the varicosil is really very big the hormone levels are normal and if you're getting a biopsy of at least hypospermogenesis on hystopathology these are the situations when a varicosal repair also can help coming to the stem cell it is all empiric as of today we have only one trial from Dr. Ranjit which is a registered trial now the indication is nonobjective esoperia with the vance of some spermogenesis severe low sperm count and somebody who was so very low like counts further suddenly they become NOA these are candidates for stem cells also coming to gene therapy it is very very new and it will take a long time for us to reach this place so I won't discuss this at this point so the contemporary trends so what is happening now so presently it is better than before like I I started my andology practice in Chennai around 4 and a half years back. When compared to that time there is a lot of microisy happening now there is more acceptance like the patient is also accepting that okay we will undergo open procedure we will take the risk. Similarly the doctors are also now okay let us try a microcy it is not available we will always go for like the next option freezing as I have seen has now the embryologist and the reproductive fraternity is very confident of usite freezing. So this option we able to give to patients so that they don't have to break their head about everything at one point. We can safely freeze those whenever it is feasible and do optimization do whatever so that we are also taking the female factor into account and there is a quest there is a increasing quest because of chat GPT etc. There is acceptance also about additional options and we are seeing a keenness on own gamuts and techniques like single sperm vification are also helping whenever we are doing preemptive sperm retrieval what are on the horizon like Dr. chronic that is isotin which we also started using now stem cells yes in some patients we are starting to use the role of PGT especially in specific circumstances a sperm search will be available in India maybe in the next 2 three years and gene therapy on the horizon so the algorithm for management we look at the partner agent desired for own gamuts choose obstructive versus non-objective very important the only point which I like to highlight here is absence of vast difference is probably the only case where you can be certain about obstructive in all other situations it is only empirical diagnosis. Maybe if there is a ejective obstruction that may be one of the other reasons or post infectious obstruction. These may be the other cases where OA is certain but along with that procedure it is always good to combine at least a tissa to see if there are normal sperms.
So that's what I have written here. We should always have a hisystopath or at least a lab sample which says that yes spermogenesis is good then we have more like uh that is more favorable uh outcome and the VA decision is like a empirical vesso epidemal anesmosis can be done only if the partner is very young and the decision to do synchronous versus preemptive sperm retrieval in non-obstructive is now coming up. Take home messages. Algorithmic approach to identify the diagnosis. Testicular volume plus FSH can give us an idea of the diagnosis. Normal FSH values do not dictate such successful sperm retrieval.
All the cost as we have seen in the presentation. Normal FSH palpable epidemis will favor an obstruction.
Congenital bilateral absent was difference with normal testicular volume plus normal FSH. This is probably the best predictor of normal sperms in the OPD. And when there is a positive carotype or positive AF. So if there is a client filter we can clearly tell the patient that for your age for your reports for your testicular size you have only this much chance. Similarly when the A is C is present we can tell them you may get sperm. If it is A or B we can always tell you will not get sperm. So a positive genetic result actually pro prognosticate sperm retrieval better. And as all IVF and fertility consultants, we should be confident about discussing the donor sperm and timing of the sperm retrieval.
So we should be able to tell them like these are your options. This is your chance whether you want to go for donor sperm now or never. And then based on that decide when you want to do the sperm retrieval and donor sperm algorithm is under the perview of the IVF consultant if the couple considers at that point or is willing at some other point.
So there are so many more things to like do in this and I thank again the IFS for this opportunity. I will take just 2 minutes to present the surgical sperm retrieval and then take questions.
Yeah. So single stage surgical spermal is abbreviated as SSSR usually. So this is what we do. So this is to understand that we don't do a PR on one day and then come back and tell that we will do micro on some other day. Our preop workup and discussion should be such that we are able to tell the patient today if you don't get sperms probably never you will get sperm. So we have to have that confidence in mind. So as I mentioned already in obstructive it is epitimal and in non-obstructive it is usually testicular source.
So this is a pizza where we use a syringe the same which was told by Dr. Sabundi in the presentation. We use a very fine needle we stabilize the testes and use the epidermal like the full epidemis. We take the fluid it can be even done under local anesthesia. And this is how the sample looks. So for somebody with esoposmia this is the magnitude of sperms and good motile sperms we can get with a tissa. This is very different from what we get on tissa.
So for tissa we can either do it under local or general anesthesia. If you are going forward with the sperm retrieval of microt magnitude then we usually do it under GA. If it is a trial tissa which usually don't prefer we always still want to do a trial microtc but still in some circumstances we will do a trial tissa. So here we use a 18 gauge butterfly scalp set. We stabilize the testice and then we perpendicularly go into the testice multi quadrant we can go and we use a 10 ml or a 20 ml syringe to hold the vacuum and take out that core which comes out like that.
Yeah.
And I already covered this testicular like teasing under the magnification of around 10 to 15x and then we look for sperms which may even be moving in a testicular sample that is very good.
Yeah. So when to do microt nonobstructive if you diagnosed it with especially testicular failure TI is negative small volume testice probably a microcy will work better. So they already told you the rational why we do a microt. So we go by midline scrotal incision. We use one incision to expose both the testice. We go in layers open the tunica. Open the testice in a transverse fashion.
So this is how the testice is bal in equatorial plane and we start doing the surgery at around 10 to 15. We are busing the tunica bleeding with the bipolar and we are able to start seeing the tubules here. This is a superficial just opening and looking if there are any dilated tubules we will take sperms from like the tubules from there. It is assess the general architecture and they assess the quality here itself. If you are able to find out areas like this which are distinctly different from the other areas then we just pick those tubules and give it to the embryologist and they will check it out and tell whether there are sperms. Already madam has told about the methods. So we will give it to madam and we will wait for the result. So then we zoom in more. We go from 10 to 15. Next we go to 20 25x and we are again looking for the same thing. Is there a focus where there are dilated tubules? So the thing we have to note here is we are looking for dilated tubules against a background of homogeneous tubules.
So that is how we keep zooming in up to 25x.
So these are very clearly different.
Okay these tubules. So this is what we are looking at.
And here also if you see when compared to these areas this is the area where there is a single dilated tub. So this is actually very small volume test is from where there is a very little area of focal spogenesis.
So if you see the great difference between the highest testice and some area where there is a dilated tube and we still go keep going we do the splitting go for lobule then go for four cotton resection we keep doing so that we explore all the areas do the hemoasis close with proline and then close the wound. So after that hard effort we may get a single sperm which is also very good for us. So again I thank you all for the patient listening.
>> Thank you very much Dr. Karthik. It was a crystal clear presentation on um in whom to do sperm retrieval techniques and how to do the techniques as well with a video presentation. Actually we wanted to ask you some questions regarding the case based discussions which you have already included in your presentation as you said but uh just one or two questions. uh in this case um uh as Amit said uh you said you already said medical management don't wait for medical management it's better to go for uh uh Tisa as soon as possible till he has the sperms this first case of madup priya where uh she was talking about u um I mean second case epidemis do you prefer surgery in these type of patients as a surgical um urologist or you would advise Tissa for these patients No, as I mentioned, whatever may be the case, we are looking at clinical findings.
>> If there is a palpable epidmus, then that is where we are looking at obstruction.
>> If there is no palpable epidemus, it is probably then based on the testicular size also. If there was a epidemic and that itself could have damaged the testice. Yes, the patient could have asosperia because of that. So, this is a tricky situation. Okay, we don't have so many epidemis coming with aospermia. M >> but if it is a block like a tuberculosis or infection then certainly there will be some findings okay we looking at obstruction >> if there is no then it is probably an effect of the infection damaging see both the sides epidemicis is very rare if it is a mums then that's a different situation where you get high FSH and we know the thing ms no primary testicular failure is a different picture bacterial infection UTA epidemic is different which is usually unilateral so bilateral lab market is presenting as non-objective is slightly rare. So whenever we see a NOA we are looking at whether there is obstruction or not. If there is no obstruction we have to go for sperm retrieval that is again based on the hormone value, testicular size and epidemal fullness. The one important thing before that is like the previous case. So Dr. Anit told that we will be giving like we will be uh what was the first question you asked regarding the first case?
First case, Amit's case that is about whether you will prefer medical management or Yeah.
>> So again mentioned in the presentation >> early and late. Yeah.
>> Yeah. Medical management comes after one microtc. So in this particular case what had happened is we did a TSA which was a trial. We did not get sperms. So we went for medical management and medical management at 3 months and 6 months we look for sperms. So the premise of medical management there was by giving in LH and FSH recominant is is the maturation error going to improve. So for that there is very little evidence that is what he also presented.
Similarly the dosage which was presented is actually 75 units LH and say I think 150 units FSH. I think the LH dose is much more and we use inibenb and 17 hydroxy proone as markers like if the 17 OP is very low then there is a role for increase like put giving LH >> there's a question about that as well sir there's a question in the chat Dr. Rajenta has asked this question. Could you please explain the role of 17 hydroxy progesterone and inhibilin B in evaluation and management of?
>> Yes. So coming to that inhibin B is a marker of a testicular marker of spermogenesis whereas FSH is a pituitary marker of spermogenesis. So if the testice is producing enough sperms okay if the spermogenesis is happening that is a like there is a B production because of which there is a negative feedback of the testes and that is why the FSH is low. So when the FSH is high we expect the inhibin B to be low. But there are some situations where inhibin B is now currently being checked as a marker which can help us to understand whether the testicular spermogenesis is improving. And the second thing if the indivin report is good then probably you will either get sperm or these testes will better respond to medical treatment. So that is the purpose of indivin 17 progesterone is applicable when we also saw Dr. Ranit's case where the oil was means he was talking about aromatization etc. We want to understand what is the level of intraesticular testosterone. So we all do serum testosterone. Many a time patient gives the sample at 11:00 p.m. like it's 11 like in the night and testosterone comes low. So we always ask for early morning testosterone that also can be low at times because of various reasons or obesity. At that point we need to have a intraesticular testosterone which is good enough for having the millu for sperm production. So 17 hydroxy progesterone is a surrogate marker of intraesticular testosterone. Remember 17 OP independent B both are not standard markers. They are new markers. So we all don't know whether this the information which we have is enough or we need to have more data. But when we are optimizing a nonobjective or a hypo hypo patient we can use the 170 HP as a marker. If the 170 HP is less than 0.5 that is an indication where you keep to give like more ovital or LHCG whatever and increase the intraular testosterone which can be monitored by uh serial 170 HP values.
For example, we have done a microtc. If the 170 HP is low, then we can optimize that 170 HP to reach the clinical range where it is around.5 to1. In this range, the increasing like there is a better chance for the millu to produce sperms.
Then on top of that we had the recominant FSH which can help in more sperm production. So it is not only about giving RFSH it is also about maintaining the testicular millu to produce like give that environment for sperm production. So this is how we differentiate and proceed towards optimization for second microis.
>> So what about the serial test? How often should we repeat to see whether it's >> yeah around 45 to 60 days once because we we titate the dose at around 45 to 60 days along with of course lifestyle changes etc which Dr. also mentioned but uh when we give the preop optimization we are we are looking at achieving target 170 HP levels which should be.5 to1 for example if there is a small test is high FSH low testosterone if the 170 HP is well in range say above 1 1.5 it means that that patient's testosterone level is okay intraesticular testo testosterone is reasonably good so there is a genetic defect that is why the spermogenesis is not happening and there waiting giving injections and then going for microt every 6 months may not make a that is no relevance for that if the 170 HP was less than 0.5 then giving injections till bringing that level to.5 and above that is uh like there you can wait otherwise waiting is not an option if 17 HP is already good to start with I think uh you understood what >> yes got it sir >> so there's one more question what was the pregnancy rate in microt say any followup needed Yeah. So there are two three questions here. So success rate of microt itself is around 50 maximum 60. It's a cohort like uh in the cohort the success rate is around 50 to 60 maximum 50%. I can tell you in our patients also but sometimes if the patient has good retrieval maybe there was an obstruction which either we didn't pick up or we didn't give that option to the patient.
So it is very difficult to tell what is the success rate of a microt but microt for standard NYA with high FSH is somewhere around 40%. That is point number one. Second point clinical pregnancy rate in these patients will be around 20 25% maximum. Third point followup is there is nothing to do regarding the testice or sperm production. But somebody who had a low testosterone to start with may require TRT initially but after 6 months that testosterone usually becomes okay. So if at all we are monitoring it should be testosterone at 3 and 6 months.
>> Um yes sir. So I think uh that's the end of questions. Uh thank you very much.
Thank you. I I thank all the speakers for the day. they have done a brilliant presentations and um I think it was a useful uh um academic session today.
Thank you. Thank you very much Dr. Ajenta.
>> Yeah. Uh dear speakers and participants and on behalf of IFS Tado chapter uh we extend our artful gratitude to everyone who made this webinar a meaningful and impactful session. A sincere thanks to the distinguished speakers for sharing their expertise and uh giving practical takeaway takeaway home points and a special thank you to all the participants for their active engagement, thoughtful questions and continuous commitment to learning and we acknowledge the efforts of the IFS Tamada chapter team for putting together this educational platform. A sincere thanks to Sahiti, Chitrakala and Shield for making this webinar possible. Uh thank you all for the wonderful webinar.
Have a wonderful evening. Thank you so much.
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