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Category: Infertility

Young Adults Male Infertility Causes & Treatment

Posted on by Dr. Ali Thwaini

Infertility is a common problem affecting young adults. At least one and six couples would be suffering from this condition. It is the inability to conceive after one year of unprotected intercourse. While traditionally fingers are always pointing towards the female partner, men are equally responsible for inFertility with 50% being caused by the male factor.

Of course, there are other factors causing infertility despite Both partners having normal parameters. When it comes to male factor infertility, there are several causes such as infections, trauma exposure to toxins, or congenital problems. Many of these factors are easily treatable, however, some might require an intervention to facilitate conception (Assisted fertilization). While this started fairly recently in the 80s with limited success, With the advancement of technology and medical sciences, success rates of dramatically increased.

Sperm harvest, though challenging, is becoming more feasible with the improvement in technology. This includes Microscopic testicular sperm extraction, Epididymal sperm aspiration, etc. The application of regenerative medicine in many aspects of healthcare is becoming more popular, however, when treating infertility, this remains to be experimental. Watch the space!

Dr. Ali Thwaini is one of the urologists and provides male infertility treatment in Dubai

Testosterone Treatment; pros and cons

Posted on by Dr. Ali Thwaini

Testosterone, a steroid hormone, helps maintain muscle, bone, and libido. Men in their 4th decade (mid-30s), begin to have less testosterone in their bodies, at an average of just under 2% per year. If that drop continues, it could lead to hypogonadism or low testosterone. This happens to 20% of men in their 60s.

Also, Metabolic syndrome; an increasingly common condition, and testosterone deficiency in men, are closely Linked. Studies have shown that Low Testosterone Levels are associated with obesity, insulin resistance, and an adverse Lipid profile in men.

Metabolic syndrome and Low testosterone are associated with increased all-cause and cardiovascular events.

Replacement of testosterone to its physiological levels produces improvement in insulin resistance, obesity, lipid derangement, and eventually sexual dysfunction along with the improved quality of Life. However, there is little evidence on the effect of testosterone replacement on mortality in men with Low Testosterone Levels.

Testosterone Replacement Therapy (TRT) aims to boost those low levels in men with T deficiency. But TRT has had its advantages and disadvantages.

Testosterone and hypertension:

Derangements in lipid metabolism play a pivotal role in the formation of atherosclerotic plaque. High total cholesterol and LDL-C are proatherogenic whereas high HDL seems to be protective against atherosclerosis. The same pathogenic process is also implicated in the development of metabolic syndrome and type 2 diabetes although elevated total cholesterol and LDL-C are not part of the definition of metabolic syndrome. Declining levels of testosterone with age is associated with a relative increase in oestrogen levels through the increased aromatase activity. The increased oestrogen levels are associated with increased circulating cholesterol and more atherogenic lipoprotein particles.


A number of studies have shown a negative correlation between testosterone levels and total cholesterol and LDL-C. A meta-analysis of 19 clinical trials in hypogonadal men reports that significant reductions in total cholesterol and LDL-C is associated with intramuscular TRT.

Studies have shown that low testosterone levels are associated with known hypertension. Conversely, men with anabolic steroid abuse are known to have an increased risk of developing hypertension.

Testosterone and Atherosclerosis:

Low testosterone level is associated with the presence of atherosclerosis. A 4-year follow-up study demonstrated that low testosterone led to increased deterioration of the atherosclerosis. This provides evidence to support the hypothesis that testosterone deficiency promotes the pathogenesis of atherosclerosis.

Testosterone Replacement Therapy (TRT) – FAQ

Are there other than low testosterone that explains sexual dysfunction?


 Yes. Low libido and erectile dysfunction, for example, have many contributing factors to rule out, including heart disease and psychological issues.

When would I know my Testosterone Replacement Therapy is helping?

Your doctor should confirm within 6 months or so whether TRT has improved your symptoms. If it hasn’t, discuss ending treatment.

Will TRT affect my ability to father children?

Yes. TRT decreases sperm production potentially affecting Men’s fertility. Upon stopping TRT, fertility will likely return. In a small number of men, infertility is permanent.

Are there other “natural” measures to elevate my testosterone?


Reducing weight ( in overweight men) and resistance exercises may help boost your levels without medication.

Extra Caporal Shockwave Treatment plus Regenerative Medicine and Treating a Male Sexual Dysfunction: An update

Posted on by Dr. Ali Thwaini

Male sexual dysfunction is an increasing modern life condition with more than 40% of men being affected as age of 40. This is further complicated by the increasing prevalence of metabolic syndrome and the sedentary lifestyle. This has led to ever increasing incidence of atherosclerosis hyperlipidemia and type two diabetes.

Natural Cures for Erectile Dysfunction

In addition to the importance of the emphasis on improving the lifestyle measures and treating a male sexual dysfunction(Mainly in the form of exercise stopping smoking minimizing the alcohol intake and adopting healthy diet), Other medications seem to help Though on a temporary basis.

Recently there has been increasing interest and more permanent and as close to natural as possible solutions for male sexual dysfunction. Below are some of them:

Low-Intensity Extracorporeal Shock Wave Therapy

LiESWT:Shockwave therapy was introduced since the early 80s with the first experience being targeted towards kidney stones. However, recently, studies have shown that microtrauma and used by shockwaves would lead to an acute inflammatory reaction of the effect of tissues with the resultant stimulation of the healing process towards normality.

This would theoretically stimulate the growth and development of small blood vessels with the resultant increase blood flow to the affected area. This has been adopted and treatment of cardiovascular diseases and other several musculoskeletal conditions.

Urology, being at the forefront of other specialties, has adopted this method and treating various mail conditions including Peyronie’s disease and Erectile dysfunction.

Although shockwave treatment as monotherapy has now been adopted at the Urology guidelines its results are marginally encouraging With an estimated success rate of around 70%. The treatment is fairly simple considering 2 to 3 weekly attendances is at the clinic with a 15-minute session per visit for up to six weeks and the results are expected between three and six months

Platelet-rich plasma cells

Another recently adopted treatment for a variety of medical conditions mainly cosmetic with the principle of using the patients’ own fluids after being purified, keeping the platelets and other essential growth factors and nutrients and possibly Stem Cells, to help regenerating and repairing the damage tissues.

While this method is widely adopted in various clinical conditions, its effectiveness in treating erectile dysfunction is yet to be determined

Whilst there are several animal studies a demonstrating the improvements of the erectile tissue following PRP treatment there are no human trials supporting the above.

Stem cell therapy:

Stem cells are “toti-potential” and their nature with the ability to grow and regenerate and eventually specialize into functional sells according to the organ they are being introduced to

There are few but reliable human studies mainly in treating men with erectile dysfunction following radical prostatectomy with the stem cell therapy and the results are very encouraging with more than 80% success in terms of improving erections and penetration until orgasm. However, the number of participants in these trials as very limited.

Stem Cells and LiESWT combined:

The aim of injecting the Stem Cells is to direct them into the targeted area with the aim of repairing and regenerating cells and resultant improvement of the function of that organ.

Stem Cells, however, need guidance to go to the affected area. There are several animal studies demonstrating and using microtrauma to the target in the organs followed by injection of Stem Cells with the resultant of higher concentration of those cells to go to the affected tissue.

Hence, logically, by combining low intensity ESWT and stem cell therapy at the same time might improve the delivery of the stem cells and the two methods would yield more encouraging results in treating erectile dysfunction.

Ongoing studies regarding the above are being carried out and the results are anxiously awaited

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Undescended Testicles: Symptoms, Diagnosis & Treatment – Dr.Ali Thwaini Urologist Dubai

Posted on by Dr. Ali Thwaini

Undescended Testicles

This is a rather common condition and is even more common in premature babies. Around one in 20 male babies is born with an undescended testicle. In about one in 70 cases, the testicle remains undescended when the child’s testicles are not in their usual place in the scrotum. Generally, only one of the testicles is affected, but on rare occasions, both testicles fail to travel to the scrotum. 

Towards the end of pregnancy, the testicles travel through a passage into the scrotum. Both testicles should be in the scrotum by the time the child is one year old.

In some children, the testicles may be in the scrotum for much of the time, but cannot be felt there because they naturally rise back into the body through fear or cold temperatures. A parent can usually find this out by putting the child in a warm bath and checking whether they can feel both testicles. If this is the case, there is no cause for concern.

Symptoms of undescended Testicles

The condition is asymptomatic for the child but the affected side cannot be felt in the scrotum. The child will not be in pain, and the undescended testicles will not interfere with any bodily function.

However, if one of the testicles becomes twisted (testicular torsion), this will be painful, either in the groin area or the abdomen, depending on the location of the testicle at the time.

Diagnosis of undescended Testicles

The mainstay of the diagnosis is by clinical examination, preferably in a warm environment in order to relax the scrofulous and allow maximum change to have a proper clinical assessment.

Aetiology

On rare occasions, the testicle does not descend due to other problems with the testicles themselves or with the male hormones. We do not know exactly why this happens, but it is not due to anything that happened.

Undescended Testicles Treatment

The method of treatment depends on the suspected cause. If the doctors suspect the testicles have not descended due to a hormone problem, they may suggest a short course of a hormone called human chorionic gonadotrophin (hCG). This is more likely to be suspected if neither testicle has descended.

If the doctor does not suspect a hormone problem, or if the testicles remain in the abdomen after the hormone treatment, the child will need a short operation under a general anesthetic called an orchidopexy.

Undescended testicles are best treated in early childhood, usually just before or around one year of age. The child’s testicles will need treatment as they do not seem to mature properly if left in the abdomen.

The amount of sperm and fertility levels seem lower in men who have had undescended testicles, and even lower if they were not treated early in childhood. This is because the testicles need to be a few degrees cooler than the rest of the body to produce sperm.

Children with undescended testicles have a higher risk of testicular cancer in the future. It is easier to check the testicles if they are in the scrotum. If the testicles remain in the abdomen or high up in the groin, this also increases the risk of testicular torsion.

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What is an orchidopexy?

This is an operation to bring the testicles down from the abdomen to their usual place in the scrotum. This is a short operation under general anaesthetic, lasting about 45 minutes. Sometimes the operation needs to be done in two stages about six months apart.

In many cases, this can be as day surgery – the child will arrive at the hospital, have the operation and be able to go on the same day. Occasionally, a child will need to stay in hospital overnight.

Penoplasty (male enhancement)


The penile enlargement procedure is seldom discussed. Men in general are private about their privates at the best of times, and when it comes to such an intimate matter, they are even more introvert.


Stem Cell Therapy in Male Factor Infertility: Research Proposal:

Posted on by Dr. Ali Thwaini

Background:

More than 10% of couples in the world experience fertility problems. Infertility, defined as failure to conceive a clinically detectable pregnancy after >12 months of unprotected intercourse, is a common condition, reported by 1 in 6 couples.

Stem cells exist as undifferentiated cells. They are present in the embryonic and adult stages of life and are considered as a source for differentiated cells that make up the building blocks of tissue and organs.

Due to their abundant source and high differentiation potential, stem cells are considered as potential new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to multiply and then are utilized in vivo to “awaken’ the dormant spermatogonia” and are theoretically a potential source to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During the past few years, considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women.

There are several sources for stem cells: Embryonic-derived stem cells (ESC), extra-embryonic derived SC, and mesenchymal derived SC. Each has their advantages and disadvantages. In this contest of male factor infertility, another source of stem cells could exit, albeit, a sparse source; this is derived from autologous Spermatogonial stem cells. Whilst harvesting them is a relatively simple procedure at an outpatient setting, and there are no ethical nor moral issues with harvesting them, they are relatively small numbers in the testis; hence, extracting them would be rather difficult and it is challenging to be maintained in culture. Moreover, there is a risk of immune rejection.

Challenges with stem cell therapy in male factor infertility:

Besides genetic factors, azoospermia also occurs due to injuries, exposure to toxicants, immune-suppressive and anticancer treatments. However, a large proportion of infertile males are diagnosed as idiopathic with unknown causes, reflecting poor understanding of the mechanisms regulating spermatogenesis and sperm function in humans.
While several sources exit to cultivate and improve stem cells for particular functions, generating pluripotent stem cells that have the potential to differentiate and undergo mitosis followed by meiosis into haploid cells remains challenging.
There have been few animal studies (particularly mice) where autologous mouse induced plutipotent cells have been produced (miPSC). Those actually were cultivated into mature spermatogonia and early spermatids. However, only a few studies made successful in producing spermatozoa in mice. This is yet to extrapolate and translate into human trials.

However, there are few human trials where a successful culture of hiPSC was achieved, resulting in spermatogonia and few spermatids.

Possible sources of stem cells:

These can be derived from either embryo of the placenta (the former might have ethical problems and both might be associated with future, though minor, risks of mutations). Other cells are derived from adult bone marrow and fat cells, which are rich in stem cells.
The function of stem cells in male factor infertility can be divided into three possible functions:

  1. Stem cells are self-homing, and when injected into the human body, they can differentiate into the cells types native to these organs and parts. In this scenario, spermatogonial stem cells (SSC), travel to their niches upon transplantation into sterile testes. The transplanted SSCs then attach to the Sertoli cells and closely connect the blood-testicular barrier (BTB) to migrate to their niche on the basement membrane
  2. The second type involves the activation of dormant and suppressing cells. The growth and development of the human body is accomplished through cell division. With age, some cells stop undergoing normal cell cycles after division and show a state of functional dormancy. Stem cells can activate dormant cells and suppressor cells and encourage them to re-enter the cell cycle, proliferating by division. This has been well demonstrated with chemotherapy-induced premature ovarian failure (POF).
  3. The third type involves the paracrine secretion of various enzymes, proteins, and cytokines to promote cell proliferation, inhibit apoptosis of functional cells, and differentiate existing tissue progenitor cells into tissue cells in order to repair damaged tissues and grow new tissues. Spermato-genesis is a process regulated by testosterone, endocrine, and paracrine secretion/autocrine factors, such as the IL-1 family.
  4. The fourth type involves the exertion of an immunosuppressive function through cell-cell contact and secretion of soluble factors, inhibiting the proliferation of natural killer cells.
  5. The fifth type involves the promotion of the recovery of intercellular signaling. The signal molecule of the cell interacts with the receptor protein on the cell membrane, causing a conformational change in the receptor and the subsequent production of a new signal substance inside the cell. This triggers a response, such as an ion permeability, cell shape change, or some other cellular function change.

There are several ways of retrieving SSC, simply shown I the figure below:

Flow chart showing different pathways of potential utilization of stem cells into spermatozoa. (Left) Somatic cells may be de-differentiated into induced pluripotent stem cells (iPSCs), and then re-programmed to differentiate through germ cell lineage via transplantation into the testis seminiferous tubules, xenografting or germline stem cells in culture. (Right) SSCs may be harvested from the testis and kept as a tissue biopsy or processed into a single cell suspension. The tissue biopsy may be treated as an organ culture, autologous graft or xenograft to proliferate and differentiate SSCs to spermatozoa. Cell suspensions may be grown in culture and xenografted, autotransplanted into the testis seminiferous tubules, or differentiated in culture to harvest spermatozoa. (m) TESE, (microdissection) testicular sperm extraction.

Procedure and protocol:

The process involves two phases: 

The first phase is stem cell harvest and preparation: this involves collecting adipose-derived stem cells from accessible parts of the patients. Traditionally, adipose cells are abundant in the abdominal fat and upper thigh. This would provide the MSC that are required for mechanisms 2-5. This would be mainly helpful for men with severe oligo-asthenospermia. They are able to produce sperms albeit in sub-fertile quality and quantity.
For men who are azospermic; in addition to the above, SSC harvest is aimed from testicular biopsy (attempted at the same time) with the aim of extracting SSC for culture.

After proper patient counseling and office preparation, under aseptic technique, diluted local anesthetic with adrenaline is infiltrated into the abdominal wall on both sides. Then we allow approximately 15 minutes for the local anesthetic to work. Afterward, we harvest the abdominal fat utilizing a special fat harvest micro needle, which is well tolerated by the patients. After achieving the desired amount of the abdominal fat, it is transferred to the Stem Cell laboratory for purification and culture purposes; a process that usually takes between two to three weeks.

For azospermic men, testicular biopsy is carried out simultaneously and SSC is sent to the lab as above.

Patients are normally well enough to go home on the same day. Patients is normally counseled for the possibility of minor discomfort and bruising in the abdominal wall (and thighs, if they were utilized for the fat harvest, in thin patients).

In the second phase, the injection of stem cells into the ovaries; after two weeks from the harvest, the patient is prepared for laparoscopic injection of the stem cells into the ovaries.

This procedure is normally carried out as a Day Case under general anaesthesia. It normally takes less than an hour. After revering from the anaesthetic, the patient is normally sent home with minimal analgesics.

Proposal:

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We aim to prospectively recruit male patients with primary infertility and have a primary testicular failure (severe oligospermia or azoospermia) and include them in the above trial.

We aim to recruit a minimum number of 30 patients.

After consent, men will enter the above trial, that includes the following:

  1. Clinic consultation.
  2. Fat harvest (usually from the abdominal wall) and testicular biopsy. These are performed under local anaesthesia in a properly equipped procedure room in the outpatient department.
  3. Samples will be taken to the official Stem Cell laboratory, located in building 64 at Dubai Healthcare City for culturing.
  4. Patients will be sent the home the same day on symptomatic treatment if needed.
  5. Patients will be invited again to the clinic after two-three weeks when mesynchymal stem cells (MSC-from fat) and spermatogonia stem cells (SSC) would have been adequately cultured and are injected back into the testes under local anaesthesia and ultrasound guidance.
  6. Patients will be sent home with analgesia and prophylactic antibiotics.
  7. Patients will be invited to the clinic two weeks later for follow up.
  8. Semen analysis will be tested in three months, with a possibility of obtaining testicular biopsy afterwards (depending the results of the semen analysis). This will be carried out in the persistence of azoospermia. The aim is to look for live spermatogonia or sperms at various stages of maturation. This will be happening in liaison with the fertility clinic for the potential of freezing if applicable.
  9. Results will be published upon written consent from the participants.

References:

  1. Vladislav Volarevic, Sanja Bojic, Jasmin Nurkovic, Ana Volarevic, Biljana Ljujic, Nebojsa Arsenijevic, Majlinda Lako, Miodrag Stojkovic. Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges. Biomed Res Int. 2014; 2014: 507234.
  2. Fang Fang, Zili Li, Qian Zhao, Honggang Li, Chengliang Xiong. Human-induced pluripotent stem cells and male infertility: an overview of current progress and perspectives. Hum Reprod. 2018 Feb; 33(2): 188–195.
  3. Jing Wang, Chi Liu, Masayuki Fujino, Guoqing Tong, Qinxiu Zhang, Xiao-Kang Li, Hua Yan. Stem Cells as a Resource for Treatment of Infertility-related Diseases. Curr Mol Med. 2019 Sep; 19(8): 519–546.
  4. Connor M. Forbes, Ryan Flannigan, Peter N. Schlegel. Spermatogonial stem cell transplantation and male infertility: Current status and future directions. Arab J Urol. 2018 Mar; 16(1): 171–180.

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