Turek on men's health
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Award-winning urologist - and pioneer in Men's Health - Dr. Paul Turek blogs weekly about issues such as infertility, vasectomy and vasectomy reversal, sexual and hormonal dysfunction and more. Keep up with the latest on this fascinating field of medicine.

Sperm from Skin? Almost!



sperm from skin.
Cool photos of artfully stained human sperm precusor cells in the mouse testis (Courtesy: Ramathal et al. Cell Reports. Epub 1 May 2014)

Can skin be turned into sperm? The answer is “yes” in mice and “almost” in man. Yup, we are one small step closer to the holy grail of making sperm from stem cells. And this time, it looks like it might happen using stem cells that are widely available for men.

What’s the Buzz?

You know that I am obsessed with helping men who have no sperm become biological fathers. When FNA mapping yields no testicular sperm, I ask men to do what they have to do to keep moving forward…but to stay tuned to the research advance as well. Honestly, I consider our latest published research a significant “moment” in the sperm-from-no-sperm continuum. And, it hinges on the great potential of good ole’ stem cells.

Where’s the Beef?

In this study, we took tiny skin biopsies from generous patients who were deemed, by the latest and greatest techniques such as sperm mapping, to have no testicular sperm. They also had good reason for there circumstance: each harbored a genetic issue called a Y chromosome microdeletion.

Then, using Nobel Prize proven technology, my collaborators at Stanford University cleverly converted these adult skin cells into stem cells. A cool, and now old-school technique in stem cell science. They then transplanted these adult stem cells into mouse testicles to see what they would do within a relatively natural and ready-made, “live” testicle. You see, stem cells like to “fit in” and typically respond to their environment or “niche” and develop into cells that suits their surroundings. When mouse stem cells are placed into mouse testicles, they develop into germ cells and, eventually, sperm. But, would human sperm develop in the mouse?

Putting human stem cells into mouse testicles, though, presents an unusual challenge. Because of obvious evolutionary divergence between mouse and man, human sperm have never been made in the mouse. So, we did not expect to see human sperm develop in this model. And we didn’t. But what we did find was both exciting and surprising:

  • Skin-derived stem cells from profoundly infertile men gave rise to early germ (sperm precursor) cells in mice, similar to cells from fertile men.
  • The degree to which infertile men made early germ cells in the mouse testicle was 5-10x less efficient than that observed with fertile men.
  • Stem cells that missed the testicular tubules and were found outside of the correct “niche” developed into tumors at high rates. Not good but important to know.

This research suggests that even men with the severest forms of infertility may actually start life with a precious few functioning germ cells, which they then lose as they age, resulting in sterility as adults. That, my friends, opens up an opportunity where there was none before. In addition, it suggests that cells other than embryonic stem cells (the mother-of-all stem cells and entirely unavailable to men) might be used to make sperm in the future. Another opportunity. Lastly, it tells us that the stem cell “niche” (here a mouse testicle) is indeed a powerful place that, if engineered just right, might allow us grow a patient’s sperm from stem cells in the future. Could our artificial testicle be that place? We’ll simply have to wait and see…

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71 Responses to “Sperm from Skin? Almost!”

  1. Nas Shah

    Hi Dr Turek,

    It’s Nas, thought I’d circle back and say what great achievement this is and what great work is being done by some great minds.

    With such efforts and advances being made on this, I assume once all the creases have been ironed out we will be able to actually implant these cells to a infertile male? Are we on the verge of a new horizon Dr Turek, I don’t expect you to be calling me next week and asking me to be on the first flight to CA but I suspect it will happen in the near future?

    Nas

    Reply
    • Paul Turek, MD

      Dear Nas, thanks for circling back and thanks for the encouragement. We are doing it for you and many others like you. You fuel this stuff, in all its glory.

      Reply
  2. Jen H.

    Dr. Turek, I’m interested to know how far away this is from becoming a reality? Months? Years? And would it work for a man with SCOS?

    Reply
    • Paul Turek, MD

      Dear Jen, Likely years away. We are making progress for sure, but it is slow. Should work fine for a man with SCOS (Sertoli Cell Only Syndrome)

      Reply
  3. Foxy

    This is incredible. Assuming that this research proceeds down a successful course, what are the chances that it would be an option for family building in the next 10 years?

    Reply
    • Paul Turek, MD

      Dear Foxy, Really hard to call. This paper alone was about 4 years of work!

      Reply
  4. Nick

    My wife showed me a article today about the clinical trials for sperm from skin cells. I would like to be on this if at all possible. Ive been told I was azoospermic and had sertoli cell only syndrome. We are having trouble finding the blog with that information in it. Can you help us?

    Reply
    • Paul Turek, MD

      Nick, my patients who (thankfully) donated their skin for the recent Cell paper on making sperm from skin were in a scientific research study, not a clinical trial. The tissue donated and the products made are not suitable for clinical use. We are not offering a clinical trial at this time that would make USABLE sperm from skin. This will take some time, possibly several years.

      Reply
  5. Jenna

    Dr Turek, I know that it would be a ‘ball park’ guess but when do you envisage this treatment becoming available? I keep seeing “years” but at the age of 25 with a partner 10 years older with SCOS I am keen to know whether this is something that may be able to help us or whether realistically it may just be a little too late.

    Reply
    • Paul Turek, MD

      Jenna, REALLY hard to say as it depends on research progress, funding and even politics. What I can say is that, after a several year hiatus, things are moving along nicely at this point. Stay tuned for more findings to be presented soon.

      Reply
  6. Mona

    Dr. Turek, when can we expect this to come life? Your effort means the world to us with new hopes and new life. Mona and surinder

    Reply
    • Paul Turek, MD

      Dear Mona, thanks for the encouragement as it constantly fuels and motivates me. Really hard to say timeline. Each of these important papers is 3-4 years of work.

      Reply
  7. Mandeep Sahi

    Hallo Dr Turek,
    My husband is suffering from sertoli cell only syndrome.We are married since 5 yrs.Last yr my husband had a testicular biopsy, which reported SCOS. We are very depressed.Now my husband is taking Homopathy treatment from india from last 9 months.But I dont know wether it will help me out or not.Please tell me if there is any ray if hope for us to have a biological child.Thanks .

    Reply
    • Paul Turek, MD

      Dear Mandeep, consider FNA mapping before trying some experimental procedure that might generate scar tissue in the testicle. A colleague of mine. Dr Michael Haeberle does mapping in Berne, Switzerland and does a fine job.

      Reply
  8. T

    Husband had a micro tese only one sample on one side. Said nothing was found dx sertoli cell and aplasia sclerosis. Would a FNA be up his
    alley or is it completely hopeless with that dx? Hoping to go through ivf soon they want to do another micro tese but before cutting on him
    Wanted a second opinion.. whats the consult fee? Really dont want to use back up sperm. Having a hard time with that. Dr is willing to freeze part of eggs if we have to go that route. Still young (28) really hoping and praying the skin to sperm will be in our time if no one can find anything in him. Its been a heartbreaking journey.

    Reply
    • Paul Turek, MD

      Dear T, sorry about your negative adventure to date. Why only mTESE on a single side? Why only a single biopsy? These questions are relevant as there may be significant side-to-side variation in sperm findings, at least on mapping. Probably others were worried about testosterone levels, but with mapping you can get similarly good information as a mTESE but without all the invasiveness and trauma. So, I would think an FNA is definitely “up his alley!”

      Reply
  9. Giselle

    Dear dr Turek, my husband was one of your candidates and actually donated skin for research at stanford due to azoospermia and negative results with fna mapping. If this was something that actually became a procedure, would you be contacting us with the good news?

    Reply
    • Paul Turek, MD

      Giselle, I want to personally thank you and your husband for generously donating your time, energy and skin (!) for this project. We will certainly contact you if we are able to make sperm from skin. Since this was scientific research, any sperm created under research protocols cannot be used clinically for IVF-ICSI. Safety studies are necessary before clinical use.

      Reply
  10. Giselle

    Dr. Turek, I know you can’t specify times and dates on this research becoming an actual approved ivf procedure, but do you think if skin sperm works it can be a clinical procedure within 5 to 10 years from now? Just wondering…. Thank you

    Reply
    • Paul Turek, MD

      Dear Giselle, I feel that 5-10 years is reasonable.

      Reply
  11. Sam

    Dear Dr. Turek, DH diagnosed with azoospermia, went directly for ICSI in 2011 but no sperms retrieved during testicular biopsy (TESA). The Gyneac termed it as primary testicular failiure ( without conducting any test).Since then we didn’t go for any further medication or investigations. Currently on thyroxine 25mcg. Kindly suggest the further course of treatment n suggest if there is any hope.WAITING EAGERLY FOR UR RESPONSE.

    Reply
    • Paul Turek, MD

      Sam, A thorough evaluation of azoospermia includes a good history and physical exam, reproductive hormones and even genetic tests. A semen analysis with an “extended search” (pellet analysis) for sperm can also find ejaculated sperm where no one thought it might be. Stable thyroid disease is an unlikely explanation for this condition and a TESA procedure is simply insufficient an examination of the testis for sperm when it is often located in pockets in nonobstructive azoospermia. Consider a visit or a Second Opinion with us.

      Reply
  12. Amy

    Is there any update on the MR Spectroscopy treatment announced a few years ago?

    Reply
    • Paul Turek, MD

      Not lately. Patents are still being pursued voraciously.

      Reply
  13. Tom

    Dear Dr. Turek, I have anorchia – I’m curious as to whether these techniques coupled with the ‘artificial testicle’ you have developed could potentially be used to aid someone like myself. Thank you for your time.

    Reply
    • Paul Turek, MD

      Dear Tom, YES! They may be ideal for you to be a biological father in the future. You are the reason we are doing this!

      Reply
  14. Sam

    Thankyou so much for your reply, means a lot to me. Actually I’m from india n I wish it was posiible for me to come to your clinic. Anyways, desperately praying for ur success.I wish that it happens asap so that the dream of many couples like us comes true. wishing u alll the best.

    Reply
  15. Nas

    FYI, I’ve been in discussions with Professor Eisenberg at Stanford University, I thought I’d let you know that in October I plan to visit him and his team to do a skin biopsy.I thought I’d assist you and your team at Stanford. Plus Prof Eisenberg was keen for me to undertake the procedure so I kindly accepted, plus I need a vacation so I thought I’d come to the US once again and no better reason than this I guess. I may say come past your practice and offer my support and say ‘hi’

    Regards,
    Nas

    – See more at: http://theturekclinic.com/sperm-skin-stem-cells-male-infertility-azoospermia/#sthash.XVSJ0nwX.dpuf

    Reply
    • Paul Turek, MD

      Nas, good to hear that others are participating in our research! Stop by and say hi!

      Reply
  16. Mark

    Dear Dr. Turek. I had testicular cancer in both testicles. I´m on TRT for 7 years now, and still not happy with it. Will the artificial testicle be able to produce testosterone?

    Reply
    • Paul Turek, MD

      Dear Mark, the artificial testicle is a laboratory device that makes sperm outside of the body. We are however, developing cell lines of Leydig cells that may, in the future, be implantable within the body and replace current testosterone therapies.

      Reply
  17. khan

    hi dr turek
    i am liveing in uk i am 46 years of age with non obstructive azoopermia small testicals consultant gynaecologist and andrologist/subspecilist in reproductive medicine and surgery said that i will have 20 0/0 of sperms retrival in about 6to8months

    Reply
    • Paul Turek, MD

      Dear Khan, with NOA you have a 60% chance of having sperm on FNA Mapping. Not sure what “20 0/0″ means.

      Reply
  18. JD

    hi Dr. Turek,
    I had prostate cancer about 6 yrs ago and been cancer free since after my prostate removed. Now I’m 68, I had vasectomy done over 35 yrs ago. My current wife and I wants to have a baby since she never have one. Do think there’s chance for us to get pregnant.? What procedure should I go through? I greatly appreciate your reply. Thanks.

    Reply
    • Paul Turek, MD

      Dear JD, Good to hear that that you are cured of prostate cancer and are now considering fatherhood! By having your prostate removed, you essentially underwent a second vasectomy in a different location (the pelvis). One thing that I can say for sure is that after having your prostate removed, a vasectomy reversal would not work to allow for natural pregnancies as you have vasectomies in two places on each side (the one in the pelvis is not reconstructable) and your ejaculate is now altered in character after prostate removal. Having said this, you could very well still be making sperm in the testicles that could be retrieved behind the scrotal vasectomy and used with IVF-ICSI to have a child. You would need some tests to help determine if this is true, including testosterone, FSH and possibly inhibin levels.

      Reply
  19. Oyibo

    Dr Turek, I am tired. Yes tired. I am 54 and still very fit. Just finished my surgery today from St Lukes hospital when Dr Silber told us the truth: Doctors at Cornell Hospital in New York had lied to me all along. Well have just 1 testicle and the only descended one had a benign tumor(never had it easy in life) which was removed in Cornell 3 years back, then did mTESE which Dr Schlegel 2 years ago and found no sperm. The problem is my doctor never informed me that what remained in my scrotum was just scares. Got the the sad news today, but i am still producing testosterone. He wonders how. He said my only option is Stem cell. My wife is so devastated. Please what do you think. Can the artificial testicle work for either of the testicles? because i seriously believe the undescended testicle is still active. Please help.

    Reply
    • Paul Turek, MD

      Dear Oyibo, that is quite a story. I honestly don’t believe that Cornell physicians are “lying,” but simply doing the best that they know how. Certainly the artificial testicle has potential to make sperm for you in the future, but it will take some time! Follow here for details.

      Reply
  20. Erik

    Hi Dr. Turek.

    I was diagnosed with non-obstructive azoospermia last year after micro-tese and FNA mapping surgeries. My Doctor was Dr. Smith at UCSF. I live in the Bay Area. Would it be possible to join your studies? I would love to volunteer and help with your research and studies.
    I know Dr. Smith is working on stem cell research related to azoospermia. Are you and him working together? I am part of his study and he is using samples from my surgeries I believe.

    Reply
    • Paul Turek, MD

      Erik, that’s unfortunate. I know Dr. Smith well as I helped to train him in the field. Many centers are doing stem cell research and that’s good for you. Everyone is taking a somewhat different approach. I am inviting men into our research who have been FNA “Mapped” and have no sperm as they have been very thoroughly characterized for our studies.

      Reply
  21. Maria Walsh

    My son was born with undescended testicles that atrophied after surgery. He produces no testosterone at all and will start testosterone therapy soon. He is 12 years old now. Is this research or current research for infertility something that applies to him?

    Reply
    • Paul Turek, MD

      Maria, Technology to non-invasively image testicles to find sperm might apply to your son. Stem cell based treatment that use stem cell sources outside the testicle may also apply. The timeframe of 10-20 years until your sons wants kids will almost certainly apply!

      Reply
  22. Sarah F

    Hi, Dr. Turek,

    What does this imply for someone with maturation arrest?

    Reply
  23. Sara

    Dr. Turek,
    Is there enough funding for the stem cell to sperm research, or do you need more? I want to contribute to the study if at all possible. Please let me know.

    Reply
    • Paul Turek, MD

      Sara, So, so kind of you. The US government is finally turning it eye toward funding this type of research. That means that many universities will be vying for money to do this research along with our privately funded venture. This is all good for patients.

      Reply
  24. Garland

    I am was diagnosed with testicular cancer and had both testicles removed. I would like to be considered for one of your scientific studies if at all possible. I am getting on TRT but am wondering if human testicles is a requirement for the application of the sperm once developed.

    Reply
    • Paul Turek, MD

      Garland, I stay up late and work hard to help men just like you. We are hoping that testicular cells may not be necessary to make patient-specific sperm.

      Reply
  25. Nas

    Hello Dr Turek,

    How are you, I hope you are well. Nas again, just popping my head back through your door to find out how progress was going with the stem cell skin studies that were published earlier this year.
    It seems only yesterday that I was given my diagnosis of sertoli cell only syndrome (doesn’t get any easier excepting this as the years go by). I do remain positive that you and your team’s work will help me and many men. I appreciate it won’t be tomorrow but god willing in the very near future?

    Any update welcome please on the subject?

    Happy holidays to you and your team.

    Regards,
    Nas

    Reply
  26. ka

    Resetting the developmental clock of human stem cells, scientists have been able to create primordial stem cells (PGCs) in the laboratory. This feat, already achieved in mice and rats, is now possible in humans because scientists discovered how to coax human stem cells to assume a more “naïve” state—a more thoroughly epigenetically “reset” state. To induce this state and go on to create human PGCs, the scientists had to recognize how techniques developed for mice and rats were unsuitable for human cells. Ultimately, the techniques the scientists developed succeeded with both human embryonic stem cells and induced pluripotent stem (iPS) cells.

    The creation of human PGCs was accomplished by University of Cambridge researchers led by M. Azim Surani, Ph.D., and Weizmann Institute of Science researchers led by Jacob Hanna., M.D., Ph.D. Together, the researchers compiled their findings and reported them December 24 in the journal Cell, in an article entitled, “SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate.”

    “We demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells,” wrote the authors. “The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline.”

    The authors emphasized that the SOX17 gene is critical for “specification,” the process whereby human stem cells are directed to become PGCs. This was a surprise as the mouse equivalent of this gene is not involved in specification, suggesting a key difference between mouse and human development. SOX17 had previously been shown to be involved in directing stem cells to become endodermal cells, which then develop into cells including those for the lung, gut, and pancreas, but this is the first time it has been seen in PGC specification. Another gene, BLIMP1, represses endodermal and other somatic genes during specification of hPGCLCs.

    Unlike mouse embryonic cells, which are easily kept in their stem cell state in the lab, human iPS cells that have been reprogrammed have a strong drive to differentiate. They often retain traces of “priming.” To remove these traces, the researchers created a method for tuning down the genetic pathway for differentiation, effectively creating a new type of iPS cell, which the researchers dubbed “naïve cells.” These naïve cells appeared to rejuvenate iPS cells one step further, closer to the original embryonic state from which they can truly differentiate into any cell type.

    Working with naïve human embryonic stem and iPS cells, and applying the techniques that had been successful in the mouse cell experiments, the researchers managed to produce cells that, in both cases, appeared to be identical to human PGCs. The researchers then further tested and refined the method. By adding a glowing red fluorescent marker to the genes for PGCs, they were able to gauge how many of the cells had been programmed. Their results showed that quite a high rate—up to 40%—had become PGCs; this quantity enables easy analysis.

    Dr. Hanna points out that PGCs are only the first step in creating human sperm and ova. A number of hurdles remain before labs will be able to complete the chain of events that move an adult cell through the cycle of embryonic stem cell and around to sperm or ova. For one, at some point in the process, these cells must learn to perform the neat trick of dividing their DNA in half before they can become viable reproductive cells. Still, he is confident that those hurdles will one day be overcome, raising the possibility, for example, of enabling women who have undergone chemotherapy or premature menopause to conceive.

    “Having the ability to create human PGCs in the petri dish will enable us to investigate the process of differentiation on the molecular level,” explained Dr. Hanna. In addition, as indicated in a press release issued by the Weizmann Institute, further research could provide answers as to the causes of fertility problems, yield insight into the earliest stages of embryonic development, enable the development of new kinds of reproductive technology.

    “Germ cells are ‘immortal’ in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next,” added Professor Surani. “The comprehensive erasure of epigenetic information ensures that most, if not all, epigenetic mutations are erased, which promotes ‘rejuvenation’ of the lineage and allows it to give rise to endless generations. These mechanisms are of wider interest toward understanding age-related diseases, which in part might be due to cumulative epigenetic mutations.”

    Reply
    • Paul Turek, MD

      Dear KA, Thanks for posting this. It is nice to see independent confirmation of our stem cell work published in Cell in May 2014 by others. Means that we are getting closer and closer to the truth.

      Reply
  27. Maria Walsh

    Hi Dr. Turek,
    I wrote in once before and have another question. My son was born with undescended testicles that atrophied after surgery. I was told he produces no testosterone and he will begin testosterone therapy soon. He is 12 now. I noticed that he started having underarm odor. Is this possible without testosterone? All the research I have done on this has confused me further.

    Reply
    • Paul Turek, MD

      Dear Maria, Boys can pass through puberty normally with fairly low testosterone levels. I am not sure how anyone could say that he “produces no testosterone” when this is true of all prepubertal boys. That statement can only be made after puberty or during a failed puberty.

      Reply
      • Maria Walsh

        Thank you for responding! After his testicles atrophied he had a blood test that came back showing that he had no testosterone. I didn’t realize that the low levels that are created in places other than the testicles would be enough to kick start puberty.

        Reply
  28. MT

    Hello Dr Turek, i recently read on sciencedaily web site significant advances into recreating primordial gem cells using human embryonic stem cells. is it good news for your artificial testicle? the article subject is : Egg and sperm race: Scientists create precursors to human egg and sperm. happy new year by the way

    Reply
    • Paul Turek, MD

      Dear MT, Yes this is good news. This recently published research from Cambridge University in England essentially reproduced what we should in our research that was published in May 2014. Such an independent confirmation of research findings is good news that the truth is being revealed.

      Reply
  29. Shiva

    Dr.Sir,Happy New Year !! I am now 54 , with SCOS ! I would like to have my biological child and one of the may patients who are eagerly waiting for your successful clinical trials ! Kindly do let us know when should we approach you for undergoing treatment sorry for poor English !)

    Reply
    • Paul Turek, MD

      Dear Hany, we are in the process of raising 600K from angel investors (and they really are angels) to continue this work. It was a good year last year for stem cells and sperm, a lot of progress was made, but there is still much more to do.

      Reply
  30. khalil

    Hello turek sir, after your successful stem cell research completion, will any crypt orchid azoospermic adult man of any age with small testicle have opportunity to make testicle larger & descended in scrotum as normal? Please tell me.

    Reply
    • Paul Turek, MD

      Dear Khalil, Certainly we hope to give patient specific sperm to any cryptorchid azoospermic adult man. However, we have no plans of making an implantable bionic testicle to put back. Currently we treat this with testicular implants.

      Reply
  31. BES

    Hi Dr. Turek,
    I have non obstructive azospermia. All my reproductive hormones are normal. My FSH and Prolactin were elevated slightly but we’re not flagged high. My Karotype and Y chromosome were normal. My testosterone was 600. I went through a TESE microdisection. No Sperm were found. The urologist said it was maturation arrest. Is this the end of the road for having a biological child? Is there any treatments to fix or reverse maturation arrest? Could there be a systemic illness causing this? It’s just a mystery and my wife and I have no answers. We don’t know why there are no sperm and everything is coming out normal.

    Reply
    • Jennifer Neeley

      Replying on behalf of Dr. Turek, the best thing to do is to get in touch with our office and get a Second Opinion. We can set it up easily and he is often able to review everything by phone to give you a real sense of where you’re at. Our number us +1 415-392-3200 or you can email us at social@theturekclinic.com.

      In health,
      The Turek Clinic Team

      Reply
  32. Nas Shah

    Hello Dr Turek

    Hope you are well, I was just wondering if there had been any progress with the skin sperm program.

    Are we any closer to getting trials in the near future.

    Thank you
    Nas

    Reply
  33. Amina Irshad

    I am also hoping for an update with this. any progress?
    for me and my husband to be able to have a full genetic child, with no donor, would be a perfect dream.

    Reply
  34. Gary

    Dear Dr. Turek,

    Please update us on the skin sperm research.

    Regards,

    Gary

    Reply
    • Paul Turek, MD

      Please see my latest update on sperm from sperm precursors recently announced in France.

      Reply
  35. m-gamal

    hi doctor turek i had undescended testicles which atrophied after the surgery all doctors left me no hope but the stem cell treatment which includes the injection of the stem cells into the testicle how is that different from the artificial testicle and i really need a solution soon. thank you

    Reply
    • Paul Turek, MD

      Dear M-Gamal, Most men with two undescended testicles have “atrophy” or testes that are smaller than normal in size. One measure of whether you may have sperm in the testes is if you are having sufficient testosterone production. So, are you taking testosterone replacement? If so, then making sperm is far less likely. If not, then you might consider FNA Mapping or mTESE to look for sperm. Stem cell technology is at least several years away from prime time.

      Reply
      • m-gamal

        hi Dr Turek, no im not taking any testosterone replacement but my medical tests that i made earlier this year indicated that my testosterone level was less than its normal range “1.6” and my FSH range was”35″ and most importantly my inhibine-B hormone “2” so due to these result will testosterone replacement will be any how sufficient, and what shall i do at the present time. thank you for your response.

        Reply
  36. m-gamal

    And due to these results may the FNA MAPPING give us any
    hope with the sperm retrieval

    Reply

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