Male Infertility: Fellowship in Reproductive Medicine

Differentiating Pre-Testicular, Testicular and Post-Testicular Causes

Now, let us see the hormonal profile and other parameters in pre-testicular, testicular and post-testicular. Because you need to identify, they will give you the scenario and investigations and we need to look for specific cause.

So, what happens in the pre-testicular and post-testicular causes that we will see. What happens to the FSH? The levels are low in the pre-testicular causes while it will be high in the testicular and post-testicular it will be normal. Then testicular size will be small in pre-testicular and testicular cases while it will be normal in post-testicular cases.

Spermatogenesis will be normal in post-testicular. Testosterone level will also be normal in post-testicular while spermatogenesis and testosterone levels will be low or this spermatogenesis will be impaired in pre-testicular and testicular cases and treatment for pre-testicular is hormonal while for testicular you have to go for ART and post testicular also there is a surgery role of mainly surgery if it is a obstruction and other option is ART so if it is a post testicular cause you will find that the FSH levels are normal testicle size is normal spermatogenesis is normal and testosterone levels are normal okay and pre testicular testicular there will be difference of the FSH okay FSH levels will be low in pre testicular cause while in testicular the FSH levels are high.

History Taking in Male Infertility

Testosterone level may be low or normal in testicular phases okay and in pre testicular it will always be low okay because FSH is also low so testicular this particular testosterone will also do okay that is how we differentiate this we have already seen the role of history in male like medical history, surgical history, fertility, sexual history, medications in medications please concentrate again nitrofenazine, cementidine, sulfasilazine, pyramidolactone, alpha blockers, methotrexate, colchicine, amiodarone, antidepressants, phenothiazines and chemotherapy so these are the drugs which they have implicated in affecting the semen parameters okay and social history also we need to take.

This particular table we have discussed so I will not go into the detail but the parameter can be asked in the SBA okay so normal volume 1.5 concentration 15 million per ml total number 39 million per ejaculate total mortality is 40 percent progressive is 32 percent normal forms 4 percent only and vitality 58 percent okay so this table you need to know.

Physical Examination in Male Infertility

Physical examination we need to check see the general habitus of the patient the secondary sexual characters generally there is a decrease in the body hair that will point out towards the androgen deficiency there may be gynaecomastia suggestive of hypogonadism height, weight, BMI is to be noted, blood pressure is to be noted then scrotal examination is to be done in a standing position and the testes we need to palpate both testes and assess for the size and look for the consistency. Normally the consistency will be firm however if it is a soft and small there is liking to be impaired aspergillosis if it is hard that is abnormal and if you cannot palpate the testes look for the groyne okay there is a possibility of the undescended testes and these cases require reference to the urology okay sometimes they may give all these clinical findings and then the groyne swelling might be there and in the option there can be reference to the urology can be the answer sometimes we are looking for only the surgical or medical options for the treatment but in EMQ sometimes the referral and they are checking whether we are doing the appropriate referrals or not and we are able to identify the cases where the referral is required so look so don’t neglect these referrals also okay or sometimes you can have the some appropriate treatment along with the referral like here the referral to the urology and there may be suppose obstructive cause then the surgical repair could be a surgical repair by the urologist will be the appropriate option okay then epidermis look for distention suggestive of obstruction there can be induration suggestive of inflammation then vas deferens confirm presence when it is present bilaterally or not absent vas deferens is seen we need to suspect a congenital bilateral absence of the vas deferens and that is seen associated with the most probably cystic fibrosis okay then varicocel more common on the left side the feeling is like a bag of worms prominent with the valsalva manual and may cause ipsilateral testicular atrophy best examine in the standing position we also need to check the penile and prostate examination there can be macropenis or hypospadias and digital rectal examination is to be carried out and look for any prostate abnormalities or semen vesicle enlargement etc.

Investigations in Male Infertility

Now coming to the investigations investigations for male infertility the first line investigation is the semen analysis and the parameters we have already discussed single sample is sufficient if it is normal but if it is abnormal you have to repeat the sample after three months however we will require immediately if there is osmosis or severe semen abnormalities in that particular case we have to repeat immediately okay so low volume what is the cause if the volume is less than 1.5 there can be retrograde ejaculation obstruction androgen deficiency or incomplete collection or there can be unejaculation also okay so for semen analysis there are certain things which we need to remember there should be abstinence of for minimum 72 hours more than five days abstinence will may lead to decrease in the motility in the semen parameters within how much time we need to analyse it should be analysed within one hour of the collection transport can be done at the body temperature level and entire ejaculate must be collected okay it should be kept at a body temperature then hormonal pattern what happens in primary testicular failure if there is a testicular failure then FSH and LH levels will be raised so we’ll go to the endocrine test okay so endocrine tests are indicated if the sperm count is less than five million per ml okay or there is osmosis or there is erectile dysfunction or low libido or suspected endocrine disorder so these are the cases in which we will go for the endocrine profile okay so what will be the pattern in primary testicular failure you will get a increase FSH LH however the testosterone level will be low that is a primary testicular failure if it is a secondary testicular failure that means the primary is pre-testicular cause there will be decrease in FSH decrease in LH and testosterone level will also be decreased if the levels are normal but there is osmosis that will suggest you of obstruction okay and if there is an increase FSH alone that is suggestive of isolated spermatogenic failure okay so testosterone is highest in the morning so when you have a borderline testosterone level you need to interpret the levels very cautiously especially if the sample is not collected in the morning and the level is borderline then it will be better to check the sample in the morning okay.

Third is a genetic evaluation so in the investigations first we have seen the semen analysis, second we have seen the endocrine parameters, third now we are at genetic evaluation. The genetic evaluation will be required if there is a severe oligospermia or azoospermia or there is a vas deferens absence okay important conditions like a Klinefilter syndrome that is 47 XXY that is the most common chromosomal cause other is a Y chromosome micro deletion okay so there is a AZF region okay azoospermia region is there okay on Y chromosome especially long arm of Y chromosome it has got this AZF region and there are three types of this region AZF A, AZF B and AZF C okay so among these three types AZF A and B they have got a poor prognosis for sperm retrieval so these patients when there is a severe azoospermia and all sometimes we go for ICSI but these patients where there is a AZF A and AZF B these are the types in micro deletion then even with the sperm retrieval there is a poor outcome okay but if it is a AZF C type then there is a good sperm retrieval so AZF A and AZF B do not offer surgical sperm retrieval okay that is why Y chromosome micro deletion is going to be important okay then congenital bilateral absence of vas deferens generally associated with the CFTR mutation that is cystic fibrosis transmembrane conductive mutation is there then we need to test for the cystic fibrosis gene and these patients will have associated abnormalities in almost 30% of the cases so when there is a congenital bilateral absence of the vas deferens two things we need to look into it one is a check for the cystic fibrosis gene and second will be the look for the renal anomalies because 30% patients will have the renal anomalies so imaging we will be doing for scrotal ultrasound for varicose series suspected tumour okay then renal ultrasound if there is a absent vas deferens also because 30% of the cases there will be renal anomalies okay. The next investigation is a testicular biopsy it will be indicated in cases of severe oligospermia or azospermia or for sperm retrieval for ICSI and to differentiate between the obstructive and non-obstructive type of azospermia that will be important the testicular biopsy will be important.

Additional Sperm Function Tests

Other sperm function tests like post-coital test, sperm penetration test, hemizonal assay these are not done and even in the NICE guideline we have mentioned these additional tests are not required okay then there are sperm fragmentation tests like SCSA okay that is test for sperm chromatin structure assay then there is a comet assay there is a tunnel assay that is terminal deoxynucleotidyl transferase mediated DUTP nick and labelling again these are for research use and they are not to be done as per the NICE guideline okay so we will not go into this particular details of this test and do not select this as an answer in the final examination.

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Management of Male Infertility

Now what we have finished the causes, the history, investigations we have finished. Now let us see the treatment options for the male infertility okay now treatment may be medical treatment may be surgical no don’t forget the lifestyle modification that is always first okay and the duration is at least for three months for the lifestyle modification then coming to the medical treatment.

Medical Treatment

Medical treatment will be effective only if there is a specific endocrine disorder such as there is a hyperplasia or hypothyroidism or there is a congenital adrenal hyperplasia okay in hypogonadotropic hypogonadism you can treat with a GnRH or gonadotropins okay otherwise there is a limited role in idiopathic male infertility so even the medical treatment will be useful only in specific endocrine disorder okay then second if you have primary testicular failure generally no treatment to restore fertility okay if there is a testicular failure either surgical treatment is in form of ART you will have to do or if you are anticipating the testicular failure when the patient is undergoing for some radiotherapy or chemotherapy you can help them by restoring the fertility like semen cryopreservation before chemotherapy or surgical sperm retrieval plus ART or use of donor sperm so these are the options which are available in primary testicular failure.

Urological and Surgical Management

Then urological surgery especially in the post testicular causes so vasectomy reversible reversal can be advised and that the success will depend upon the surgeon skill technique and the time since vasectomy okay so patency generally as the duration increases there is a reversal is chances are reduced okay and it may be because of the anti-sperm antibodies and epididymal obstruction okay then second is a surgical sperm retrieval surgical sperm retrieval site can be testes or epididymis so testicular we have TESA, TESA or micro TESA and epididymis we have MESA and PESA technique okay then for surgical sperm retrieval we have indications such as obstructive ozoospermia, severe male factor infertility, ejaculatory failure and success rate in cases of obstructive ozoospermia it is 100% while in non-obstructive cases around 50% success rate is there. ICSI outcomes are better with obstructive ozoospermia done in tertiary centres with cryopreservation. Third is a in the surgery we can think of varicocel repair however NICE does not recommend for fertility treatment okay so NICE has not recommended repair of varicocel for the from fertility point of view what does the evidence says there is an improvement in semen parameters however there is a controversial role in the pregnancy benefit okay it may increase testosterone in a hypogonadal men.

Assisted Reproductive Techniques

Then other option for male infertility is a assisted reproduction in which we have IUI and IVF and ICSI so these are the only options which are available in the assisted reproduction so IUI indications actually on this slide there are many indications which I have mentioned but what indications we have discussed along with the NICE guideline you remember those indications only when there is a physical disability, sexual dysfunction, psychological issues or same sex couples okay so or infection so these are primary indications for the IUI okay here they have mentioned about the mild male factor infertility, immunogenic infertility, erectile dysfunction, hypospadias so pertaining to the male infertility the talk article gives these indications okay then washed sperm placed in the uterus and success rate per cycle is around 8 to 16 percent NICE recommends up to 6 cycles of unstimulated IUI and aim is to reduce the multiple pregnancy risk okay that is why this unstimulated cycles are used then IVF and ICSI these are the other options which are available in male infertility IVF in mild male factor can be used while severe male factor go for ICSI then in ICSI there is a use of single sperm which is injected especially in cases of oligospermia, osteoarthritis, oespermia, IVF failure this ICSI is useful and success rate is around 33 percent per embryo transferred in ICSI okay so that finishes the topic of male infertility.