Functional but not yet fully matured sperm, taken from the testicular tissue using a surgical procedure, can also be used for successful fertility treatment using the ICSI method.
TESE makes parenthood possible for couples where the man’s semen has no sperm, or only sperm unsuitable for ICSI treatment (e.g. “dead” sperm). Where there is no sperm in the semen (azoospermia), we distinguish between obstructive azoospermia (OA) and non-obstructive azoospermia (NOA).
OA: The sperm cannot travel through the seminal ducts (e.g. in the area of the epididymis or vas deferens). Sperm formation (spermatogenesis) in the testicles is intact. The most common causes of OA are vasectomy (surgical occlusion of the vas deferens), inflammation or congenital seminal duct malformation. Ejaculation disorders, for example with diabetes mellitus or following lower abdomen surgery, can also lead to symptoms of OA.
NOA: The testicular tissue and/or spermatogenesis is defective. Approx. 1% of all men are affected. A whole range of factors may be the cause for this condition, including congenital absence of germ cells, previous undescended testicles, inflammation, chromosome disorders, hormonal hypofunction, previous chemotherapy and/or radiotherapy and - not as rarely - high-dosage treatment with testosterone.
The procedure takes the form of an out-patient surgical intervention, lasting approx. 30 minutes. In most cases, it is carried out under general anaesthetic via an approx. 2 cm long incision in the skin of the testicle. The tunica vaginalis, underneath the skin, is then prepared and the tunica albuginea is exposed. Scratches of 3-4 mm are made at one or more sites, and the protruding testicular tissue is removed with fine scissors. Generally, 5-6 tissue samples (biopsies) measuring about the size of a match head are taken from each testicle. One of these biopsies is placed into a fixative for later histological evaluation (e.g. to exclude the possibility of an early-stage testicular tumour). The remaining samples are placed into culture medium and prepared for the “post-operative TESE test” procedure (see below). After the removal of the tissue, the various layers of the testicle are closed with absorbable sutures. Patients can be discharged around 3-4 hours later.
The rate of complications (e.g. formation of haematoma in the scrotum) requiring subsequent surgical treatment is approx. 1-2%. In most cases, there is no subsequent deficiency in the male sex hormone (testosterone).
Before the patient is discharged, the most important step of the treatment concept takes place in the laboratory - the attempt to identify sperm in the biopsies. The patient thus finds out on the same day whether the TESE was successful.
There are various methods and techniques for this. We favour the “wet prep method”, whereby the tissue is placed directly on a slide and squashed gently for microscopic viewing. As the microstructure of the semen-forming tissue in the biopsy is hardly changed, an experienced specialist can verify the presence of small areas with spermatogenesis very quickly and with great certainty from individual biopsies.
If sperm are identified, cryopreservation is carried out (cooling to -196°C) on the whole preparation. This procedure leads to practically no cell loss. The cryopreserved samples can be thawed at a later point if needed, and the sperm used for ICSI. In most cases, several preserved samples, which will keep almost indefinitely, are available. This generally provides an opportunity for complete family planning.
If there are no genetic findings to contraindicate surgery (e.g. certain Y-chromosome microdeletions), the strategy of the surgical tissue sampling is based on the medical history and current hormonal situation. FSH (follicle-stimulating hormone), secreted from the pituitary gland, and inhibin B, produced in the testicles, are particularly important “marker hormones”. If the levels of both hormones are within the normal range, tissue samples can be taken from one site on the testicle. However, if there are deviations (FSH too high, inhibin B too low), several (multilocular) biopsies are recommended, from different areas, as in this case an uneven testicular tissue quality must be expected (Spiess et al., 2008).
OA (normal FSH and inhibin B): sperm identified in approx. 80-90% of cases. In the remaining 10-20%, there is most often a germ cell maturation arrest, i.e. the level of sperm development required for ICSI is not reached.
NOA (FSH elevated, inhibin B lowered): sperm identified in approx. 30-65% of cases (Schulze et al., 1999). With NOA cases, the chances of success depend on the method of the post-operative TESE test and the competence of the investigator. Unfortunately, in most clinical studies on TESE, these factors are not paid sufficient attention.
Over a period of 6 years (2010-2015), we were able to achieve almost identical pregnancy rates per egg retrieval cycle for the treatment approaches using IVF (direct addition of sperm to eggs), ICSI with ejaculated sperm and ICSI with sperm from TESE samples: 27.5%, 30.4% and 31.6% respectively.
Unfortunately, not all pregnancies following assisted reproduction result in the birth of a child. The corresponding birth rates per retrieval cycle (from 2010 to 2014) for the three treatment forms in our clinic were: 19.9% after IVF, 22.5% after ICSI with ejaculated sperm and 22.6% after the use of TESE sperm.
The “chances of success” for ejaculated sperm and cryopreserved/thawed TESE sperm are identical under ICSI conditions.
Recent studies have suggested a correlation between an increased DNA fragmentation rate in ejaculated sperm and increased early miscarriage rates. In a doctoral thesis under our supervision, it has been shown that the DNA fragmentation of mature spermatids / testicular sperm in the testicles is very low (Duhnke, 2011). It could therefore be considered that a TESE attempt is worthwhile for couples who have experienced repeated early miscarriages for no identifiable reason. However, this treatment approach is still experimental at present.
In recent years, the so-called “micro” TESE (Microdissection Testicular Sperm Extraction) has been increasingly put forward as the method of choice for testicular sperm retrieval. This is a relatively time-consuming, invasive procedure, during which the testicle is completely exposed and dissected across its full length. The doctor then attempts to identify possible areas of spermatogenic activity under the surgical microscope. Most of the available scientific papers on the topic report increased TESE success with the microsurgical technique. However, these data are based on a comparison of the “success rates” for TESE vs. micro-TESE for the individual author of the paper. But there are significant differences between research groups in terms of the reference value alone (result of conventional TESE).
On comparing the published micro-TESE results with our own data from the less invasive conventional TESE technique, no advantage of the microsurgical procedure could be found.