Premature ejaculation

Premature ejaculation is common. It is when ejaculation occurs too soon during intercourse. The normal duration of intercourse is between 5 and 6 minutes, but this can vary.

It is not unusual to have premature ejaculation once in while. If it occurs frequently then you may need help. Premature ejaculation can be caused by prostate problems, medications, anxiety, stress and relationship issues.

It is important to seek help to ensure there are no underlying medical conditions.

We now offer new therapies for premature ejaculation including Fortacin Spray. To find out more about our Andrology and Mens Health services, please call us on 01925 202180 or email us at info@reproductivehealthgroup.co.uk

Vasectomy reversal

We undertake vasectomy reversal on a regular basis using magnification techniques which provide success rates of up to 95% for those patients who are within 10 years of vasectomy.

A consultation is usually undertaken with your partner; sometimes it may be that your partner will need a female fertility opinion. If the latter is the case then your partner will be referred to a female fertility specialist, before any vasectomy reversal is undertaken.

What is a vasectomy reversal?

You have previously had a vasectomy for contraception. You have now decided that you wish to have this reversed so as you can try to have children with your partner. The tube that carries the sperm from the testis to the penis is called the vas deferens; this is what is cut at the time of a vasectomy. A vasectomy reversal procedure involves putting the previously cut ends of your vas deferens back together.

This is done under a general anaesthetic and takes approximately 2 hours. The scrotum is opened to access the area. At the time of surgery your surgeon will try and put back together the tubes in the most appropriate place so as to allow sperm to travel through again. Several stitches are placed to join the tubes on each side. These stitches are very fine, almost as fine as your hair, so to ensure that they are placed properly we use magnification. If this operation is done using the naked eye then the result may not be as good.

Why do I need a vasectomy reversal?

With your partner, you have chosen to have a child. Having had a vasectomy before, this is not currently possible using natural methods. If you wish to have children using natural methods this is the best option for you.

What are the alternatives?

  • Sperm retrieval and ICSI
  • Adoption
  • Donor Sperm
  • Not to have children 

To find out more about vasectomy reversal and our other Andrology and Mens Health services, please see here: https://www.reproductivehealthgroup.co.uk/andrology-mens-health/

Unexplained Infertility

It can be very confusing for patients to be told by their IVF specialist that they have ‘unexplained infertility’. They find it hard to believe that infertility can still be unexplained despite the medical and technological advances that exist today.

The truth is however that despite cutting edge medical technology, there are some things which still cannot be accurately determined or diagnosed. But the good news is that despite not knowing the exact nature or cause of infertility, it can still be overcome. Unexplained infertility can be treated and couples can become parents. Sometimes, specialists may not know the full reasons behind a problem but are still able to offer a solution and this is certainly true of unexplained infertility.

Only after conducting all the relevant investigations first should unexplained infertility be diagnosed and an appropriate treatment plan considered.

Learn more about unexplained infertility here.

The role of antioxidants in male infertility

Whilst several causes of male infertility have been recognised, in the majority of men the precise mechanism remains unknown. Many studies of such idiopathic cases at the molecular level have highlighted the significant role of “Oxidative Stress”.

This entails a state of imbalance between reactive oxygen species (ROS), aka “free radicals”, and antioxidants as an established factor in male infertility. Sperm are particularly vulnerable to DNA damage and accelerated cell death.

Antioxidants exhibit a beneficial effect in reversing sperm dysfunction. Supplementation may include the Vitamins C, E and B9 (Folic Acid), the trace elements Zinc and Selenium and the substances Carnitine, Coenzyme Q10 and N-Acetyl Cysteine. They have been shown to:

  • improve semen parameters (concentration, motility and morphology)
  • reduce sperm DNA fragmentation
  • improve clinical pregnancy rates
  • improve live birth rates

However, the heterogeneous nature of various studies, including the use of different antioxidants at different concentrations and in different combinations, hamper our ability to implement an ideal treatment modality. Proper diagnosis and treatment are difficult.  Antioxidants must be chosen so that they work in synergy and with some selectivity for the male reproductive tract. Overdoses and self-medication with antioxidant formulations that use random ingredients and dosages may be counterproductive and impair fertility. At RHG, we provide advice on when and how to use supplement combinations.

Eight things to ask your fertility clinic

1. How does the clinic decide which treatments to choose?

Through a thorough consultation with the individual or couple involved, including examining medical and reproductive histories, and by carrying out relevant tests and investigations, your consultant will be able to identify which course of treatment is the right one for you.

View RHG’s range of  fertility assessment packages here.

2. What tests will I have to have?

There are a number of tests that you can expect to have as your consultant looks to identify what may be causing any fertility issues. An initial fertility assessment on either one or both partners in the relationship can help to ensure any issue is dealt with without paying for needless treatment if a simpler or more cost-effective solution can be found.

3. Does the clinic work with patients to ensure the treatment for them is the most suitable?

Some fertility clinics are simply IVF clinics, with this being the treatment option offered to all patients. However, this may not be the best option for everyone. At RHG we will only recommend the best care pathway once we have carried out all the appropriate investigations.

4. What treatments are available?

There are a variety of treatments available, from IVF (In vitro fertilisation), where eggs and sperm are brought together outside the womb in a laboratory, to IUI (intrauterine insemination). For IVF treatment, there are also a number of different techniques, such as ICSI (intracytoplasmic sperm injection) and IMSI (intracytoplasmic morphologically selected sperm injection).

5. What success rates does the clinic have?

Before you start out, you want to know that you have chosen a clinic that has high success rates in helping people to achieve their goal and become successfully pregnant.

View RHG’s latest success rates here.

6. What are the costs involved?

You can view our clear and transparent fertility price list here.

7. Are women with specific conditions accepted at the clinic?

If you are affected by a specific issue, you may find that not all clinics are able to offer you treatment. At RHG we are able to treat all gynaecological and infertility conditions under one roof at our Cheshire based Centre for Reproductive Health.

8. What makes the clinic different to the others?

In our case, it is our dedicated integrated fertility and women’s health hospital, one of the first ever in the UK. Every detail was designed by our consultants and embryologists, using their extensive experience to ensure that our patients receive the best possible care, using the very latest technology in a state of the art environment.

If you would like to organise a fertility consultation with us to discuss any of the above, or additional questions you may have, please do contact us on 01925 202180 or email us at info@reproductivehealthgroup.co.uk

Polycystic Ovary Syndrome (PCOS) and Fertility

Polycystic Ovary Syndrome (PCOS) is a common cause of infertility in women due to its impact on ovulation. Changes in hormone levels affect the way in which your body produces and releases eggs and can cause irregular periods. If regular ovulation is not occurring this can make it difficult to achieve a successful pregnancy.

Can I still get pregnant if I have PCOS?

This is a question that we are asked regularly at RHG and the answer is yes! PCOS is one of the most common types of female hormone disorder and is one of the leading causes of infertility, but that is not to say that you can’t have a baby if you suffer from PCOS. The question is, which treatment is right for you?

Treatment options for PCOS and infertility

There are a number of potential treatment options including conventional fertility treatments, such as IVF, but also natural, nutritional measures, improving diet and making changes to lifestyle.

For some women, simply making changes to their weight is enough to completely resolve their symptoms and restore a regular menstrual cycle. The best diet for women with PCOS who are overweight is one that promotes stable levels of blood sugars and lowers insulin levels. It is recommended to see a nutritionist who can recommend an appropriate programme.

For other women whose lack of ovulation is the main issue, ovulation induction can be used to help stimulate the development of mature follicles at just the right time in the cycle.

Improve your fertility potential

RHG’s experienced specialists can advise on the best treatment programme to help alleviate symptoms and improve fertility potential.

Embryo implantation failure tests

Embryo implantation failure is part of what we called the dreaded diagnosis of unexplained infertility where people are putting out so much time, effort, money, emotion and yet it keeps repeating with each IVF cycles.

For unexplained failure of implantation we would say that it is usually two cycles of really good embryos that are transferred, with proper number of embryos, easy transfer, the cycle looking great but the outcome is either not getting pregnant or even worse those early slowly rising HCG levels where everybody knows it’s just a matter of time until it ends in a miscarriage. At RHG, we try to give her a chance of having nausea, vomiting, breast tenderness, and a 20-30% chance of caesarean section because we believe she is going to make a good incubator if we can select the best investigation and treatment approach.

The treatments we offer help us tailor her next treatment cycle closely to her needs. Around one-third of implantation failure cases are due to embryo abnormalities. And we know sometimes an embryo can be perfect and still can’t implant due to her womb lining. Our extensive recurrent implantation tests help us look into the embryo factors, paternal factors, endometrial tests, and maternal factors. Briefly they assess the mother’s clotting profile, immune screening, levels of uterine natural killer cells and autoantibodies. Hysteroscopy is a test which allows us to assess the womb cavity by direct viewing and carry out treatments if required. High levels of sperm DNA fragmentation have been linked with miscarriage and treatment options such as testicular sperm extraction for ICSI can benefit those couples.  Preimplantation genetic testing helps us select the best euploid embryo while time lapse imaging of the embryo (Embryoscope) monitors embryo cell divisions and these cell time points help predict further development potential. Overall, they allow us to select the best embryo which will be more likely to implant.

Putting Male Health First

When a couple fails to conceive, males are found to be solely responsible in 20-30% of cases and contribute to almost 50% of cases overall.

Professor Luciano Nardo, founder and medical director of Reproductive Health Group (RHG) in Daresbury, has dedicated his entire career to helping couples who are seeking to conceive a child and argues that while female reproductive health is often at the forefront of a woman’s mind, men can easily overlook or ignore their own reproductive health.

He says: ‘Couples that have been unable to achieve conception after one year should be investigated. One in eight couples have problems with conceiving their first child and the fact that in just under half of these there will be a male factor that is contributing demonstrates it is important always to consider the male.’

‘Sadly, the provision for male infertility within the NHS is rather poor, with facilities still very female orientated both locally and nationally. Ideally, all diagnostic and treatment procedures should take place under one roof, not least because of ethical and legal concerns over the movement of sperm samples between locations. At RHG we have all the expertise and clinical facilities required to undertake all relevant research and procedures. We have also recently appointed both Professor Vijay Sangar, Consultant Urological Surgeon, and Mr Arie Parnham, Consultant Urologist and Andrologist (specifically male diseases and conditions) and specialist in male fertility.’

The first step for any couple seeking support with infertility is to see a specialist, of course, but what does this mean for the male partner?

Mr. Parnham says: ‘The first thing we must do is a full health check. Studies have shown that men with impaired semen parameters are also more likely to suffer from poor health. We also undertake a semen analysis. If this is abnormal we would repeat the test and if still abnormal then perform blood tests to check hormone levels and whether there might be some genetic abnormality – with appropriate genetic counselling, of course.

‘Some patients will need further tests, including ultrasound imaging of the testes or prostate, MRI scans or vasography. It might all sound rather scary when listed like this, but treatment can be as simple as making some lifestyle changes – stopping smoking, weight loss, improved exercise etc – though on occasion minor surgery may be necessary and in that case we have all the facilities we need at RHG.

‘It’s sad, but there is still a lot of stigma associated with male infertility and very little research in this area, although this seems to be changing. Many men view infertility as a challenge to their masculine identity and so either ignore the issue or find it very difficult to talk about. RHG understands this and has private facilities and counsellors to help.’

Professor Nardo adds: ‘By bringing Vijay and Arie to the clinic, we can offer a unique, bespoke, integrated service where all aspects of male and female infertility are addressed in parallel under one roof, allowing efficient investigation, treatment and excellent outcomes.

‘I believe we should start educating men from a young age about awareness of their reproductive health. By paying no attention until the time they are seeking to conceive, what might initially have been small problems can escalate and cause much heartbreak down the line.’

Professor Sangar agrees: ‘We offer a full male reproductive health check at RHG, whether you are currently actively to trying to conceive, or not. This check-up is, I would argue, something men should consider as a regular thing. It can not only pick up on infertility issues, but also signs of more serious issues.’

Management of infertile men with no sperm


Part One – Introduction

Azoospermia affects 1% of all men and accounts for 10-20% of males who present with infertility. It is defined as the complete absence of sperm in the ejaculate. The largest groups are: abnormally descended testes (17%), Klinefelter’s syndrome (14%), infertility of unknown cause (13%) and previous vasectomy (5%). Essential to the workup of male infertility is the semen analysis. According to WHO specimen collection guidelines, two samples (if the first is abnormal) are required. The goals are to determine the underlying cause and subsequently either treat it if possible; or retrieve sperm for assisted reproductive techniques. All investigations and treatment options are available at the Reproductive Health Group or can be organised by our Urologists at nearby hospitals.

The clinician needs to attempt differentiation between obstructive azoospermia (OA) and non-obstructive azoospermia (NOA).

Obstructive (or post-testicular azoospermia, OA) accounts for 40% of azoospermia and can result from a multitude of causes which may be due to a structural (e.g. vasectomy) or functional problem (e.g. failure to ejaculate). Men with OA classically have normal sex hormones (testosterone and FSH), normal testes on clinical examination and normal ultrasound.

NOA can be classified as pre-testicular (the rarer cause; often due to abnormalities of the hypothalamus or pituitary gland in the brain), or testicular; leading to impaired formation of sperm within the testes. Pre and post-testicular azoospermia are often treatable, whereas testicular causes (apart from azoospermia associated with varicocele), are generally not correctable.

Causes of Obstructive Azoospermia (OA)

Structural

Iatrogenic / traumatic

  • Previous vasectomy (most common cause of OA)
  • Inguinal hernia repair (especially with mesh)
  • Pelvic or scrotal surgery (e.g. hydrocele repair, orchidopexy)

Congenital

  • Congenital bilateral absence of the vas deferens (CBAVD)
  • Young’s syndrome (sinus and chest infections and azoospermia)
  • Mullarian or Wolfian duct cyst/ ejaculatory duct cyst

Infective

  • Chlamydial or gonococcal infection

Functional

  • Drugs, spinal injury, neurological, previous pelvic or abdominal surgery

Causes of Non-obstructive Azoospermia (NOA)

Pre-testicular (hypogonadotrophic hypogonadism)

Congenital

  • Kallmann’s syndrome (inability to smell, delayed puberty)

Acquired

  • Previous surgery of pituitary gland
  • Treatment with testosterone
  • Granulomatous illness
  • Haemochromatosis
  • Autoimmune diseases

Testicular (hypergonadotrophic hypogonadism)

  • Klinefelter’s syndrome
  • Maldescended testes or torsion
  • Varicocele
  • Tumour
  • Drugs – steroid abuse, chemotherapy, gonadotoxins
  • Infection – mumps
  • Idiopathic (i.e. unknown cause)


Part Two – History and Examination

For men referred to the Reproductive Health Group for azoospermia, your Andrologist will carefully explore your medical history and carry out a physical examination as required. Subsequently, various investigation might be required (described in Part 3), before a management plan can be suggested.

History suggestive of Obstructive Azoospermia (OA)

  • Previous surgery (vasectomy, inguinal, scrotal, retroperitoneal)
  • Genitourinary infection
  • Chronic bronchopulmonary infection
  • Family history of cystic fibrosis
  • Normal libido

History suggestive of Non-Obstructive Azoospermia (NOA)

  • Delayed development/ onset of puberty
  • History of undescended testes or testicular torsion
  • Previous gonadotoxic treatments (including chemotherapy and radiation)
  • Environmental exposure to gonadotoxins
  • Treatment with (or abuse of) exogenous testosterone
  • Headaches
  • Visual disturbance
  • Pituitary surgery
  • Low libido

Examination Findings suggestive of OA

  • Normal male characteristics
  • Inguinal or scrotal scars
  • Normal testis size, consistency and position
  • Epididymal fullness or cysts
  • Vasa may be absent
  • Vasal defect from vasectomy
  • (if present assess for position and length of defect and for sperm granuloma)
  • Prostatic or midline cyst on digital rectal examination

Examination Findings suggestive of NOA

  • Lack of male characteristics
  • Small atrophic testes
  • Undescended testes
  • Varicocele
  • Gynaecomastia (breast swelling)
  • Visual field defects


Part 3 – Investigations

Semen analysis

Semen analyses are vital in establishing the quality and quantity of sperm in infertile patients. According to the WHO, at least two evaluations should occur over a two months period.

Men with certain forms of obstructive azoospermia (OA) may have a reduced ejaculate volume (less than 1.5mL). Obstruction in the prostate will result in low semen volume with low pH and fructose levels. Normal volume implies non-obstructive azoospermia (NOA) or obstruction of both vasa or epididymes.

Hormone profiling

Follicle stimulating hormone (FSH), luteinising hormone (LH) and early morning testosterone (T) should be measured. OA results in normal hormonal levels, whilst pre-testicular and some testicular abnormalities may have abnormal levels.

Low Testosterone with elevated FSH and LH may be found in primary testicular failure (where the testes have stopped working properly, for unknown reasons). Should there be an abnormality of these hormones, an endocrinology referral should be strongly considered. Pre-testicular infertility (with low Testosterone and low FSH and LH) should be further investigated with prolactin levels and imaging of the pituitary gland (such as a brain MRI).

Genetic testing

Genetic testing is an important part of the workup for azoospermia, especially when considering NOA. In these cases, there is an increased frequency of chromosome abnormalities – for example Y-chromosome microdeletions and Klinefelter syndrome.

• Sex chromosome abnormalities

Klinefelter’s syndrome (KS) is the most common chromosomal abnormality (affecting one in 600 males) and accounts for approximately 15% of NOA. The “classical” form (47 XXY) accounts for 80-90% of KS cases. In the remaining 10-20%, so called “mosaics” are found. Clinically, these men have small firm testicles (<5cc) and may demonstrate normal virilisation, but also scant or female hair distribution. Testosterone may be normal or low, whilst FSH is increased.

• Y-chromosome abnormalities

Three microdeletions on the long arm of the Y Chromosome account for about 7% of severe oligospermia/ azoopsermia. AZFc varies between azoospermia and oligospermia. There is a 70% chance of finding sperm with AZFc and thus micro-TESE and ICSI are indicated. If intracytoplasmic sperm injection (ICSI) is utilised, these aberrations will be passed onto male children. In certain countries, pre-implantation sex selection of female embryos may be considered.

With AZFa or AZFb microdeletions, it is highly unlikely that any sperm will be found. Thus, microscopic surgical sperm extraction (micro-TESE) is not indicated and ICSI will fail.

• Autosomal disorders

Cystic fibrosis (CF), an autosomal recessive disorder, is due to a gene mutation. (Children can only develop cystic fibrosis if BOTH parents have the mutation.) It is associated with congenital bilateral absence of the vas deferens (CBAVD), which affects 1% of infertile men. Therefore, in infertile men with no vas on either side, testing for CF in both parents and referral to a genetic counsellor should be offered.

Imaging Options include ultrasound (US), magnetic resonance imaging (MRI) or more invasive methods including vasography.

Scrotal Ultrasound

Scrotal US can verify the size of the testes and look for the absence of structures as well as for evidence of obstruction such as spermatocele or dilatation of vas/ epididymis/ rete testis. It is also useful if the physical examination is suboptimal due to body habitus or testicular pain, or if examination findings are equivocal. In patients with NOA, scrotal US should be strongly considered as there is an increased risk of testicular cancer.

Transrectal Ultrasound

Transrectal US can identify ejaculatory duct obstruction. Aspiration of the seminal vesicles can be performed. Sperm aspirated in such manner can be used for ICSI.

Renal tract Ultrasound

Renal tract US should be performed when unilateral absence of the vas is noted – 20% will have no kidney on the same side.

MRI

MRI can be employed to identify ejaculatory duct or prostatic cysts. It enables evaluation of the vas deferens and seminal vesicles and may indicate the site of obstruction.

Vasography

Vasography is an invasive investigation used to identify the site of obstruction. It is rarely used in purely diagnostic situations and requires microsurgical skills.  It is an open procedure, usually undertaken as part of a therapeutic intervention to reconstruct an abnormality.

Testicular biopsy

Testicular biopsy may be helpful in differentiating OA from NOA in men with at least one palpable vas, normal testis size and normal FSH. It is is possible that performing a diagnostic biopsy may reduce the subsequent success rate of sperm retrieval via micro-TESE for NOA because of bleeding, haematoma and fibrosis. Therefore, should testicular biopsy be performed, having the ability to simultaneously cryopreserve sperm for use in ICSI is desirable.

Key Points for Determining the underlying cause of azoospermia

++ Most azoospermia can be determined via history, examination and first-line investigations

++ CFTR mutation should be tested for and genetic counselling offered for men with bilateral absent vasa. The female partners should also be counselled prior to using the sperm of these men

+++ Men with NOA should have genetic counselling with karyotyping and screening for AZF aberrations

+ Transrectal US +/- aspiration of seminal vesicles is important to exclude ejaculatory duct obstruction (EDO), particularly in men with low ejaculate volume

++ If one or both vasa are absent, renal US should be offered

+ Testicular biopsy may help to differentiate between NOA and OA in equivocal cases but has the potential to decrease the chances of sperm retrieval on subsequent Micro-TESE in cases of NOA: hence should be undertaken in units with facility to simultaneously cryopreserve sperm for use in ICSI.

Evidence level:

+++ strongly evidence-based
++ less strongly evidence-based
+ not evidence-based but clinically understood / clinical opiniona


Part 4 – Treatment: Reconstruction

Treatment of azoospermia depends on the underlying cause. Essential to determining definitive management is the evaluation of both partners. Female fertility factors (e.g. age, prior fertility, polycystic ovarian syndrome, endometriosis), the number of children desired, success rates of various treatment options, and even financial considerations, may impact the couple’s treatment choice. An understanding that treatments such as vasovasostomy (VV), vasoepididymostomy (VE), and varicocelectomy can take 3-6 months for optimisation of seminal parameters, may also influence a couple’s decision.

Reconstruction for Obstructive Azoospermia (OA)

OA can be overcome by reconstructive surgery, to relieve an obstruction and to restore sperm to the ejaculate. Alternatively, sperm can be harvested from either testis, epididymis or vas, in conjunction with assisted reproductive techniques such as IVF or ICSI.

Reconstruction includes vasovasostomy (VV), vasoepididymostomy (VE), and transurethral resection of the ejaculatory ducts (TURED).

Vasovasostomy (vasectomy reversal)

Despite the numerous factors to be considered, there are no controlled trials investigating whether surgical repair or sperm harvesting with assisted reproduction (AR) provide the better option. However, it appears that unless there are specific dictating female factors, vasovasosotomy provides a more cost-effective option with a higher delivery rate.

This procedure can be achieved by various techniques using an operating microscope or loupes. The principles of repair include a water-tight, end-to-end, tension-free joint with good blood supply.

Although a surgeon may plan for a VV pre-operatively, the decision to undertake VV or VE should be made intra-operatively by analysis of vasal fluid. After prolonged vasal obstruction (longer than 10-15 years), secondary blockage of the epididymis from high pressure can occur, requiring a connection between the vas deferens and the epididymis.

Besides duration since vasectomy, there are several factors that need to be taken into consideration – such as sperm granuloma, length of proximal vas and the microscopic appearance of fluid expressed from the proximal vas (using microscopy).

The following findings will promote VV as the choice of reconstruction:

• Copious clear fluid from the vasal stump on the testicular side

• Motile sperm in this fluid

• Whole sperm or sperm parts in this fluid

• Length greater than 2.7cm

• Sperm granuloma (a small nodule of scar tissue)

If there is absent vasal fluid or the fluid is thick and creamy, VE should be performed regardless of vasal length or presence of sperm granuloma.

An overall VV patency rate has been reported up to 86%, with an average pregnancy rate of 52%. The duration of obstruction and female fertility are important predictive factors in semen return and pregnancy rates.

If the female partner is aged 35 to 39, pregnancy rates are reported as 54%. However, once aged 40 years or older, these rates dramatically reduce to 14%.

Vas reversal outcomes

Obstructive Interval (years)Return of sperm ratePregnancy rate
< 397%76%
3-888%53%
9-1479%44%
>1571%30%

Vasoepididymostomy (VE)

VE is indicated for epididymal obstruction with patency rates of up to 80%, and pregnancy rates of 13-56% being reported. This procedure is technically very challenging and time-consuming. Use of an operating microscope is essential.

Transurethral resection of the ejaculatory duct (TURED)

TURED is a procedure which opens an obstructive midline cyst in the prostate or resects part of the prostate itself, dis-obstructing the ejaculatory ducts. The procedure can be performed at the same time as vasography (cannulation of the vas and injection of a dye).  Once the duct is adequately resected, a tinge of dye can be seen emerging in the prostate.

The procedure improves sperm numbers in 50% of previously azoospermic men, yielding a pregnancy rate of 25%. Complications include re-obstruction, rectal injury, retrograde ejaculation into the bladder and urine reflux, which may affect sperm quality and cause infections.

Part 5 – Treatment: Sperm harvesting, varicocele, hormonal optimisation

Sperm harvesting for obstructive and non-obstructive azoospermia (OA and NOA)

Several targets for sperm retrieval are possible – testis, epididymis or the vas. There are also different methods of harvesting sperm from these areas. It can be undertaken percutaneously (aspiration or biopsy) and with an open technique (with or without the operating microscope). The choice about which area to target and the means by which this is done is based on clinical presentation, available equipment and the skills of the surgeon.

Some options include:

  • Testicular sperm aspiration (TESA)
  • Conventional testicular sperm extraction (C-TESE)
  • Microsurgically assisted TESE (Micro-TESE)
  • Percutaneous epididymal sperm aspiration (PESA)
  • Microsurgical epididymal sperm aspiration (MESA)

Obstructive azoospermia

For men with OA, reconstruction may be possible and this should be considered. Without reconstruction, sperm retrieval is necessary to use with IVF/ICSI to achieve a pregnancy. Most men with OA have normal sperm production capabilities. Thus, any approach to the testis, epididymis or vas should yield sufficient numbers of sperm.

TESA may be all that is necessary. However, although a simple procedure, it yields the lowest sperm numbers which, and may not retrieve enough motile sperm for IVF. In these cases, a PESA or MESA can be utilised.

PESA involves percutaneous passage of a fine needle through the epididymis whilst applying negative pressure through a syringe. It is simpler and more accessible than MESA, as it does not require microsurgical training. However, it is not as precise, resulting in lower retrieval rates. Complications are usually minor, but can include haematoma, spermatocele and fibrosis and scarring at the injection site. PESA may therefore potentially compromise future reconstruction attempts.

MESA can procure sperm in OA in 90% of cases and pregnancy rates range from 40% to 60%. MESA has the advantage of being able to accurately target the epididymal tubules which, under the operating microscope appear favourable for containing motile sperm. Reconstruction might be possible at the same setting.

There is conflicting evidence as to the best choice for sperm retrieval techniques for OA. The American Urological Association (AUS) Best Practise Statement suggests there is no difference in outcome for IVF or ICSI in relation to the method of sperm harvest and therefore the choice of method is dependent on local facility and surgeon factors. The American Society for Reproductive Medicine guidelines suggest that MESA yields the best pregnancy rates in OA, but requires microsurgical expertise so cannot be recommended for all cases.

Non-obstructive azoospermia (NOA)

Depending on the underlying pathology, up to 70% of men with NOA, will harbour sperm within the testes and, if found on harvesting, live births can result in 30% to 50% of such couples. In men with NOA, the AUA Best Practice Statement recommends open surgical testicular sperm retrieval with or without microscopic magnification for patients with NOA. Cryopreservation of sperm should be offered at the time for use with ICSI.

Micro-TESE involves the use of a surgical microscope at 15x to 20x magnification, targeting larger and more opaque testicular tubules. This improves sperm retrieval rate. The majority of studies show statistically better retrieval rates ranging from 45% to 57% for micro-TESE compared with conventional TESE. Micro-TESE appears to claim a lower complication rate compared with conventional TESE, and there is a smaller volume of testicular tissue removed.

Conventional-TESE involves opening of the testois and excision of several tubules, often from several regions of the testis. The specimen is then sent for processing and immediate microscopic evaluation. Complications include haematoma whilst large volume TESE can result in permanent reduction in testosterone levels.

TESA involves percutaneous aspiration of sperm from the testis with a needle and syringe. Multiple passes are made. The benefits include no need for microsurgical training, rapidity and non-invasiveness. Retrieval rates range from 10-30%. It appears likely that TESA have sperm retrieval rates that are inferior to that obtained with TESE.

Hormonal optimisation

(For hypergonadotropic hypogonadism and subsequent sperm retrieval)

There have been several publications suggesting that optimisation of the hormonal environment improves sperm retrieval rates in patients with NOA.  These studies are particularly applicable to patients with Klinefelter’s Syndrome but may also be applied to non-Klinefelter’s patients.  Different protocols have been suggested and may include consideration of testosterone to oestradiol ratios, or improvement of FSH levels. The most common drugs used are Clomiphene Citrate, Anastrazole, Tamoxifen and/or hCG for 3-6 months prior to attempted sperm retrieval.

Risks of AR techniques

Whilst IVF and ICSI are available, there appear to be slight additional risks to both mother and child. The risks of pre-term labour (10% versus 8%), low birth weight (7% versus 4.7%) and birth defects (5% versus 4%) is higher in babies born following IVF compared with naturally conceived babies.

Key points for sperm harvesting

  • The type of azoospermia and surgeon preferences determines the method choice ++
  • OA should be treated if possible; simple sperm retrieval techniques can be employed +
  • NOA usually requires open surgical sperm retrieval with micro-TESE having the highest sperm retrieval rates ++
  • Repeated biopsies may reduce subsequent sperm retrieval rates ++
  • AR may incur slight absolute increases in major birth defects ++

Evidence level:

  • heavily evidence-based +++
  • less substantively evidence-based ++
  • not evidence-based but are clinically understood +

Varicocele

Recent data suggests a benefit for treating varicoceles in patients with abnormal semen parameters and a clinical varicocele. In patients with a clinical varicocele and NOA, the main potential benefit is for motile sperm to be detected in the ejaculate which may obviate the need for a (micro) TESE. Return of sperm into the ejaculate has been reported in 12 studies and range from 21-56% of azoospermic men post varicocele repair. However, these studies are retrospective and uncontrolled. Furthermore, most men still require a micro-TESE to retrieve adequate sperm for ICSI despite a varicocele repair. The absence of a varicocele may enhance spermatogenesis and improve the success rate at micro-TESE.

The choice of treatment of a varicocele is based on the skill set of the treating doctor, but based on two meta-analyses, microsurgical varicocelectomy has demonstrated the highest success rates with the lowest recurrence and complication. This has led some authors to suggest that a microsurgical varicocelectomy is currently the gold standard for varicocele repair.

Treatment of pre-testicular infertility

For these conditions, referral to an endocrinologist is recommended. In hypogonadotrophic hypogonadism, there are some effective medical treatments including androgen replacement and human chorionic gonadotrophin (hCG) combined with follicle-stimulating hormone (FSH). Pulsatile gonadotrophin releasing hormone may be used if there is a pituitary cause. Whilst testosterone replacement is justified for other symptoms (such as low energy levels and libido), there is no role for this to improve fertility. Exogenous testosterone can reduce gonadotrophin levels and hence impair spermatogenesis; and should be ceased during fertility treatment. Prolactin producing pituitary adenomas can be treated medically (microadenomas) or surgically (larger adenomas).
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Part One – Introduction
Part Two – History and Examination
Part 3 – Investigations
Part 4 – Treatment: Reconstruction
Part 5 – Treatment: Sperm harvesting, varicocele, hormonal optimisation
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