Abstract
Surgical sperm retrieval (SSR) is used in situations where sperm suitable for fertility treatment cannot be obtained by other means, principally from the ejaculate. Even sperm obtained from cryptozoospermic samples can be used for intracytoplasmic sperm injection (ICSI) and the major indication is therefore azoospermia. On occasion, sperm suitable for treatment cannot be recovered due to problems with ejaculation and if techniques like penile vibratory stimulation or electro-ejaculation fail in men with conditions such as spinal cord injuries, or if sperm suitable for ICSI cannot be recovered from the post-orgasm urine in men with retrograde ejaculation, then SSR may be needed. A rare indication would be an ‘emergency’ retrieval procedure where a patient cannot for psychological reasons, produce a sperm sample on the day of oocyte retrieval and there are therefore no sperm available to proceed to treatment. As an alternative to cancelling the cycle, some authors have reported success by utilising SSR, although oocyte cryopreservation would be an appropriate alternative approach. In cases of obstructive azoospermia (OA), reconstructive male genital tract surgery where applicable, should be considered. Some authors describe excellent outcomes for vaso-vasostomy particularly in situations where the interval between vasectomy and reversal is short and the female partner is young with no fertility issues [1].
1 Why Perform Sperm Retrieval?
Surgical sperm retrieval (SSR) is used in situations where sperm suitable for fertility treatment cannot be obtained by other means, principally from the ejaculate. Even sperm obtained from cryptozoospermic samples can be used for intracytoplasmic sperm injection (ICSI) and the major indication is therefore azoospermia. On occasion, sperm suitable for treatment cannot be recovered due to problems with ejaculation and if techniques like penile vibratory stimulation or electro-ejaculation fail in men with conditions such as spinal cord injuries, or if sperm suitable for ICSI cannot be recovered from the post-orgasm urine in men with retrograde ejaculation, then SSR may be needed. A rare indication would be an ‘emergency’ retrieval procedure where a patient cannot for psychological reasons, produce a sperm sample on the day of oocyte retrieval and there are therefore no sperm available to proceed to treatment. As an alternative to cancelling the cycle, some authors have reported success by utilising SSR, although oocyte cryopreservation would be an appropriate alternative approach. In cases of obstructive azoospermia (OA), reconstructive male genital tract surgery where applicable, should be considered. Some authors describe excellent outcomes for vaso-vasostomy particularly in situations where the interval between vasectomy and reversal is short and the female partner is young with no fertility issues [1].
Some studies have suggested that there may also be occasional situations where SSR techniques may be indicated where sperm is available in the ejaculate. The Cornell group examined their outcomes in patients with cryptozoospermia where the couples had had at least one round of ICSI treatment using ejaculated sperm and one round of treatment using sperm recovered by microdissection testicular sperm extraction (MicroTESE). In an understandably small number of cases examined in this retrospective analysis, by comparing the two approaches that were performed closest (temporally) to each other, a significantly higher fertilisation rate was identified in the MicroTESE group. Furthermore, a higher pregnancy rate was found when more than six sperm were seen in the ejaculate, following the post-preparation spin down examination of the samples. Due perhaps to the small sample size, no other significant findings were identified [2].
A multicentre study from Europe recruited couples who had experienced recurrent treatment failure using ICSI, in cases where the male partner had a high percentage of DNA fragmentation in his sperm. Sperm taken by testicular biopsy in this group showed a significantly lower percentage of sperm DNA fragmentation and also a significant number of clinical pregnancies. Although other studies have now shown similar results, as with the Cornell study, it is perhaps difficult to apply the results of this work to more general andrological practice. However, it is important to remember that SSR can be considered in situations other than azoospermia [3].
2 The Development of Surgical Sperm Retrieval
The introduction of ICSI and the first reported pregnancies using this technique [4] has revolutionised the care of couples with male factor subfertility. It paved the way then for sperm to be recovered surgically from the testes and to be used to treat couples affected by male factor subfertility. Prior to this, the only options available for couples were male genital tract reconstructive surgery in situations where it was an option (ie vaso-vasostomy, vaso-epididymostomy, or in the rare occasion of ejaculatory duct obstruction, trans-urethral resection of the ejaculatory ducts) or using donor sperm. It is worth mentioning that despite the rise of assisted reproductive techniques, these procedures are still valuable (and indeed cost-effective) in appropriate cases.
The mechanism of the azoospermia indicates what type of procedure can be employed to recover sperm for ICSI. Techniques to recover sperm from men with OA are nearly always successful, and so the techniques used to recover sperm from such cases are usually minimally invasive. It is more difficult to recover sperm surgically from men with sperm-production problems that have resulted in non-obstructive azoospermia (NOA) and the chance therefore of achieving biological paternity is much lower. The introduction of the MicroTESE technique, which utilises optical magnification to directly inspect the testicular parenchyma, by Schlegal and co-workers in Cornell University [5], has significantly increased the chance of recovering sperm from men with NOA. This modern technique is considered the gold standard in terms of recovering sperm in this particularly difficult-to-treat category of couples, when compared to single-site or multi-site TESE. Indeed, as sperm can be recovered in approximately half of non-obstructive cases where single site TESE failed to recover sperm and a third of cases where multi-site TESE has failed, the case for performing these less effective procedures in such men is seriously weakened [6]. A further study examined the outcomes in men undergoing MicroTESE SSR with those undergoing multi-site biopsy. This study showed that the recovery rate in the MicroTESE arm was significantly higher than in the multi-site TESE arm [7].
3 Investigating the Azoospermic Man prior to SSR
The detailed assessment of male fertility is covered elsewhere in this book (Chapter 3), but a few key points should be reiterated. The history and examination findings can explain the mechanism or even, on occasions, the precise cause of the problem. It is unfortunately not uncommon to encounter patients who have never been examined before, to then find relevant abnormalities like absent vasa deferens, large varicoceles or low volume testes, which can explain the problem. Occasionally scrotal examination may reveal suspicious lumps. Testes cancer is the commonest solid malignancy in young men. Men with fertility problems are at an increased risk of developing it, (possibly due to the shared aetiology of Testicular Dysgenesis Syndrome) a fact that should be explained in the clinic, along with instructions regarding testicular self-examination [8]. It is mandatory to examine the genitalia of men who have significant male fertility problems and those who are to undergo SSR, to ensure that there are no surprises on the day of the procedure in terms of the patient’s anatomy and to ensure that the patient is suitable for such a procedure. It is not unheard of in patients admitted for sperm retrieval who have not been examined before, to be found unexpectedly to have cryptorchidism when they are on the operating table. This situation should never arise. Furthermore, a patient who cannot tolerate his testes being examined is unlikely to tolerate a local anaesthetic procedure well either, and finding this out in advance could prevent a procedure being abandoned on the day.
A clear explanation for the problem is of great significance to the patient. A high FSH will confirm a sperm-production problem and in an azoospermic male, indicates a non-obstructive aetiology. The reverse however is not necessarily true as a significant number of men with a normal FSH and azoospermia can also have a non-obstructive aetiology (late maturation arrest). In this situation, the FSH level is within the normal range as the biological trigger for inhibin B release is the pachytene stage of meiosis, not the production of mature sperm, meaning that the patient could have a normal FSH (and normal-sized testes) with no sperm production.
The testosterone level of patients should be recorded pre-procedure as patients with a sperm-production problem not uncommonly have a low testosterone. This should never be corrected in advance of the procedure with testosterone replacement therapy, which can, by interfering with the hypothalamo-pituitary-gonadal axis, inhibit endogenous testosterone production and thus interfere with any spermatogenesis that may be occurring. Some clinicians use HCG, FSH or clomifene to boost sperm production, but this is controversial [9]. Whilst karyotype or (where indicated) cystic fibrosis testing can provide useful aetiological information, it is helpful also to perform Y microdeletion testing prior to attempting SSR, in situations where the underlying reason for the azoospermia is not known. This is to exclude the Y microdeletion patterns AZFa and b, which are believed to be incompatible with successful sperm retrieval as they result in complete Sertoli cell–only syndrome and complete maturation arrest respectively, in affected males. (Those men who bear the more common defect AZFc have hypospermatogenesis and do therefore have a chance of undergoing successful SSR, although the couple should be aware that such a defect would be passed on to any male children that they may have through ART).
Appropriate assessment of the azoospermic man allows him to be put into (in most cases) a mechanistic category, which will then determine what the most appropriate surgical sperm retrieval procedure would be, assuming of course that the couple wish to undergo ICSI treatment. Some couples in whom a genetic problem is identified decline SSR and furthermore, some couples prefer to opt for donor sperm treatment even when SSR is a possibility. The clinician’s role is to provide the couple with appropriate information within a supportive environment, which will enable them to make what is the right choice for them. Some couples require more information and support and although men are sometimes reluctant to seek it, should be offered counselling.