When is sperm retrieval recommended?

Sperm samples for in vitro fertilization (IVF) are typically obtained via ejaculation and collection of semen, which contains sperm. However, sometimes obtaining sperm via ejaculation is not possible, or a semen sample does not contain enough sperm. In the case of ejaculatory dysfunction, treatments such as medications, urinary sperm retrieval, prostatic message, penile vibratory stimulation, and electroejaculation are typically tried first. If these are unsuccessful, surgical sperm retrieval can be used.

Here are some reasons why patients may choose surgical sperm retrieval:

• ‍Obstructive azoospermia (OA): A blockage (obstruction) within the male reproductive tract, which leads to complete absence of sperm within the ejaculate (azoospermia).^i,ii Causes can be congenital abnormalities (such as congenital bilateral absence of the vas deferens), trauma, infection, previous vasectomy, or unknown.ⁱⁱⁱ
• ^‍Non-obstructive azoospermia (NOA): The inability of the testes to adequately produce sperm. Causes can include primary hypogonadism (abnormal testicular function that impairs sperm production) or secondary hypogonadism (which results from impaired hormone release from the pituitary gland or hypothalamus in the brain).^iv
• ^‍Anejaculation: When a patient experiences an orgasm but does not ejaculate or expel semen. Causes include obstruction of the ducts that produce semen, trauma, injury during surgery, radiation, or nervous system problems such as Parkinson’s disease, multiple sclerosis, and spinal cord injury.^v
• ^‍Anorgasmia: Inability to achieve an orgasm and ejaculate. Causes include certain medications (most commonly antidepressants), hormonal abnormalities, psychogenic stressors, or neurologic conditions.^vi
• ^‍Retrograde ejaculation: Ejaculation during which semen is not expelled out of the urethra but backwards into the bladder due to impaired contraction of the bladder muscles. Causes may be side effects from medications or procedures, diabetes, or unknown.^vii

What types of sperm retrieval procedures are available?‍

These are the main types of sperm retrieval procedures available:

• Testicular sperm aspiration (TESA)
• Percutaneous epididymal sperm aspiration (PESA)
• Testicular sperm extraction (TESE)
• A subset of TESE known as microsurgical/microdissection testicular sperm extraction (microTESE)

Following sperm retrieval, the sperm can be used to fertilize a female’s eggs (oocytes) using IVF with intracytoplasmic sperm injection (ICSI), which involves the embryologist selecting a sperm to inject directly into the mature oocyte. ICSI is used because sperm retrieval samples have lower numbers of sperm compared to typical ejaculated semen samples. Sperm retrieved via aspiration or extraction cannot be used for intrauterine insemination (IUI) or at-home insemination because the sperm are either non-motile or not fully motile and are too few for these methods to be successful.

What is testicular sperm aspiration (TESA)?

TESA is also known as testicular fine needle aspiration (FNA). It involves introducing a needle into the testes and moving it in various directions while applying suction to aspirate the contents into a syringe. The fluid that is aspirated typically contains components of seminiferous tubules as well as sperm. The contents are inspected for sperm under a surgical microscope.^viii

TESA is indicated for both obstructive azoospermia (OA) and non-obstructive azoospermia (NOA).^ix Like all techniques, there are some advantages and disadvantages:

• ‍Advantages: TESA is a simple procedure to perform and does not require more advanced training or equipment compared to other techniques. It can be completed under local anesthesia.^x Because TESA removes components of the seminiferous tubules along with sperm, it can be used for diagnostic purposes to identify the underlying cause of azoospermia (in addition to using the sperm retrieved for IVF with ICSI).^xi
• ^‍Disadvantages: Because TESA is completed “blindly” by moving the needle in different directions, the clinician does not know for certain which structures are being punctured by the needle. This randomness increases the risk of testicular damage and can lead to bleeding or hematoma formation following the procedure.^xii,xiii Furthermore, TESA may be less successful in some situations (particularly in the case of NOA) than testicular sperm extraction (TESE) or microTESE^xiv because the samples are taken blindly, and less tissue is removed with the needle than in TESE.

What is percutaneous epididymal sperm aspiration (PESA)?

PESA also involves aspirating fluid from the epididymis using a specialized needle. It differs from TESA in that the aspiration needle is inserted into the epididymis instead of the testes in order to retrieve the sperm. During PESA, the clinician feels for the head of the epididymis (which is situated at the top of the testes) and advances a needle through the epididymal duct while applying suction to aspirate fluid into a syringe. The fluid is then examined under a surgical microscope to identify if sperm are present. If they are not, the needle can be reintroduced to the epididymis at a slightly different location, and the aspiration can be attempted again.^xv PESA is only performed in cases of obstructive azoospermia (OA); it is not used for patients with non-obstructive azoospermia (NOA).^xvi

• ‍Advantages: PESA is a simple procedure that can be repeated multiple times if sperm are not retrieved. It does not involve an open surgical technique and can be done under local anesthesia.^xvii
• ^‍Disadvantages: During PESA, the epididymal duct is located only by touch and therefore the clinician may miss the duct during an attempt. Like TESA, there is a chance of puncturing a blood vessel leading to bleeding during the procedure. Finally, PESA can only be used for patients with obstructive azoospermia (OA), and it has a lower sperm retrieval rate than TESE in some cases.^xviii

What is testicular sperm extraction (TESE)?

TESE is a surgical sperm retrieval procedure that is used to take a sample of the interior of the testes (known as the testicular parenchyma). Sometimes TESE is termed “conventional TESE” (c-TESE) to distinguish it from microTESE. The conventional procedure is completed under direct visualization, without the use of a surgical microscope.^xix,xx

During a conventional open TESE procedure, a small incision is made through the skin of the scrotum, the underlying muscle layer, and the outer covering of the testes.^xxi,xxii Small samples of the testicular parenchyma are obtained, and the layers of the outer coverings are closed with stitches. The samples are then examined under a microscope for the presence of sperm and to help confirm a diagnosis.^xxiii,xxiv

Sometimes the samples are evaluated as the procedure is taking place so that additional samples can be taken if few to no sperm are found. Other times, the samples are sent to the andrology laboratory and evaluated immediately after the procedure. Depending on the case, either a single incision or multiple incisions are made in the testicle through which multiple biopsies can be taken.^xxv,xxvi

• ‍Advantages: TESE can be performed using local anesthesia, often combined with intravenous sedation or epidural anesthesia.^xxvii It is considered more effective for non-obstructive azoospermia (NOA) than aspiration techniques and can help with the ^xxviii,xxix Since it is not a “blind” technique like TESA, bleeding can be identified if it occurs during the procedure and can be addressed immediately.
• ‍Disadvantages: It is more invasive than aspiration techniques. Intratesticular hematoma is common in TESE, but usually resolves on its own.^xxx Pain, swelling, and potential for infection are also possible risks. In some cases of TESE, a larger volume of testicular fluid is removed to obtain sperm, which may lead to reduced blood flow and tissue in the testes (called devascularization) and lower testosterone levels.^{xxxi,xxxii,xxxiii,xxxiv}

What is microTESE?

A more advanced form of TESE, known as microsurgical/microdissection TESE (microTESE), may also be used for sperm extraction. MicroTESE increases sperm retrieval rates by individually selecting the seminiferous tubules from within the testes that are most likely to contain sperm. These tubules are typically dilated and opaque in appearance.

The procedure is completed under general anesthesia. During microTESE, the scrotum, muscle layers, and outer testicle covering are opened to reveal the parenchyma of the testis. The tissue is then examined under an operating microscope, and the larger seminiferous tubules are isolated. Samples of these healthy-appearing tubules are taken, processed in the operating room, and typically examined during the procedure for the presence of sperm. If no sperm is present, the same procedure may then be attempted on the other side. The layers of the testes and scrotum are then stitched closed.^xxxv

Many providers consider microTESE to be the gold standard for sperm retrieval in patients with non-obstructive azoospermia (NOA) because, in these patients, sperm are often only produced in small healthy segments of the testes, which are best identified with a microscope.^xxxvi,xxxvii

Other sperm retrieval techniques

In patients with anejaculation (inability to ejaculate semen) who do not have azoospermia, there are other techniques aside from extraction or aspiration that can be used to collect sperm. This type of anejaculation is typically the result of a neurological condition such as a spinal cord injury (SCI).

Penile vibratory stimulation (PVS)

During PVS, a vibrating device is placed against the glans (head or tip) of the penis to stimulate ejaculation. Once ejaculation occurs, the semen is collected. In individuals who have anejaculation due to a spinal cord injury affecting the higher part of the spine, PVS is the most effective sperm retrieval method for obtaining the most total motile sperm. It is also less invasive compared to electroejaculation (described below). However, PVS may not be as effective for individuals with a lower spinal cord injury.^xxxviii

PVS is generally a safe, non-invasive procedure, though there is a risk of causing irritation to the skin of the glans. In individuals with a spinal cord injury above the level of T6 (a higher SCI), there is also a risk of autonomic dysreflexia, which is a severe reflex response that causes the blood pressure to rise rapidly. Individuals at risk are typically treated with a medication to lower blood pressure before PVS, and their blood pressure is monitored during the procedure.^xxxix

Electroejaculation (EEJ)

During EEJ, a probe is placed in the rectum and used to deliver electrical stimulation, which induces ejaculation by activating the pelvic muscles.^xl Sometime with EEJ, retrograde ejaculation will occur in the bladder. If it does occur, sperm must subsequently be retrieved from the urine.

EEJ is effective at nearly all levels of spinal cord injury.^xli Like PVS, there is a risk of autonomic dysreflexia in those with spinal cord injuries above T6. Therefore, these patients should be given medication to lower blood pressure prior to EEJ. EEJ is completed under general anesthesia in patients that still have pelvic sensation (despite a neurological injury) to prevent pain during the procedure.^xlii

Prostatic massage

A physician performs prostatic massage by inserting a finger into the rectum and massaging the prostate and seminal vesicles to push out semen. While this technique is inexpensive and does not require specialized equipment, it is less effective at obtaining sperm.^xliii

How successful are sperm retrieval procedures?

Success rates for sperm retrieval procedures vary depending on the specific method used and the patient’s individual circumstances. For example, success rates can be impacted by these factors:

• Underlying cause of male infertility
• Age of the patient
• Experience and skill of the healthcare provider performing the procedure
• Timing and frequency of the procedure
• Use of other fertility treatments in conjunction with sperm retrieval

Overall, success rates can vary widely and should be evaluated on a case-by-case basis.

Testicular sperm aspiration (TESA) success rates

TESA has been shown to be very effective in males with obstructive azoospermia (OA), such as following a vasectomy. Evidence suggests that TESA is less effective in cases of non-obstructive azoospermia (NOA).  A study by Jensen et al (2016) found the sperm retrieval rate to be 100 percent in males with OA (all 82 patients with OA had sperm retrieved), compared to a sperm retrieval rate of 30 percent in males with NOA (38 out of 125 patients with NOA had sperm retrieved).^xliv

TESA has also been shown to be effective for males with severely decreased sperm motility, called severe asthenozoospermia (also known as asthenospermia). Most patients with asthenozoospermia have enough healthy ejaculated sperm to be used for IVF with ICSI. However, some individuals with severe or complete asthenozoospermia only have sperm in their ejaculate that are not viable and cannot be used.^xlv Some healthcare providers believe that these patients may benefit from a TESA or TESE to collect healthier sperm. In a study of 28 males with severe asthenozoospermia (progressive motility less than 1 percent), they found that the sperm retrieval rate (SRR) was 100 percent, and sperm was retrieved from one of the testes only.^xlvi

Percutaneous epididymal sperm aspiration (PESA) success rates

PESA has been shown to be very effective in males with obstructive azoospermia (OA).  A study by Esteves et al (2013) of 146 males with OA found that the cumulative sperm retrieval rate (SRR) was 97.3 percent.^xlvii For individuals with congenital bilateral absence of the vas deferens (one cause of OA), the SRR was 100 percent, compared to 96.6 percent in males who had undergone a prior vasectomy, and 96.3 percent in individuals who had a previous infection causing OA.

Note: PESA is not performed for individuals with non-obstructive azoospermia.^xlviii

Testicular sperm extraction (TESE) and microsurgical/microdissection TESE (microTESE) success rates for non-obstructive azoospermia (NOA)

A systematic review of seven studies by Deruyver et al (2013) found that among patients with non-obstructive azoospermia (NOA), there was a significant increase in the sperm retrieval rate (SRR) with microTESE compared to conventional TESE.^xlix They found that the SRR with conventional TESE ranged between 17 to 45 percent, and from 42.9 to 63 percent in the microTESE group.

Another study in males with NOA, by Zhang et al (2021), found that microTESE overall had a 46 percent SRR.^l The researchers found varying SRRs for microTESE performed for patients with the following individual conditions causing NOA:^li

• ‍Kleinfelter syndrome: 44.7 percent
• ‍AZFc microdeletion: 73.6 percent
• ‍Cryptorchidism (undescended testes): 75 percent
• ‍Previous mumps and bilateral orchitis (inflammation of the testes): 100 percent
• ‍Idiopathic NOA (unknown cause): 30.7 percent

Testicular sperm aspiration (TESA) vs conventional TESE vs. microTESE for non-obstructive azoospermia

To date, there is a lack of agreement on the best sperm extraction technique to treat non-obstructive azoospermia (NOA) due to mixed results from research and few randomized controlled trials.^lii,liii,liv

A systematic review and meta-analysis by Bernie et al (2015) compared the sperm retrieval rate in males with NOA undergoing TESA, conventional TESE, and microTESE.^lv This study found that microTESE was the most effective sperm retrieval technique, and that it was 1.5 times more effective for sperm retrieval than conventional TESE (SRR 52 percent vs. 35 percent). In comparison to TESA, conventional TESE was approximately two times better than TESA at retrieving sperm (SRR 56 percent vs. 28 percent).

Success rates of other non-surgical techniques

It is important to note that non-surgical sperm retrieval techniques are used for individuals with difficulties ejaculating, as described earlier. They are not used to retrieve sperm in males with azoospermia.

Penile vibratory stimulation (PVS) has been shown to be more effective in males with a higher spinal cord injury (SCI). The success rate of PVS with a SCI above T10 is 86 percent, compared to 21 percent with a SCI below T10.^lvi

Electroejaculation (EEJ) can be highly effective at sperm retrieval for those with neurogenic anejaculation. A study by Giulini et al (2004) found that in males with infertility related to SCI, 32 out of 34 patients (94.1 percent) were able to achieve ejaculation with EEJ.^lvii In other studies, it has been found almost 100 percent effective.^lviii

Prostatic massage is less consistently effective at retrieving sperm from males with an SCI. Arafa et al (2007) found sperm was successfully retrieved in only 22 out of 69 patients (32 percent) with an SCI using prostatic massage.^lix

What happens after sperm retrieval?

If sperm retrieval is successful, it must be followed by intracytoplasmic sperm injection (ICSI) to fertilize a female oocyte (egg). The process of ICSI involves injection of the sperm directly into the oocyte, which creates an embryo that can be transferred into a female’s uterus.^lx

There is evidence to indicate that it is worthwhile repeating microTESE in males with non-obstructive azoospermia (NOA) who underwent a previous unsuccessful microTESE. Özman et al (2021) found that 18.4 percent of patients with NOA and a previous unsuccessful microTESE had a successful sperm retrieval on a repeat.^lxi

After sperm is retrieved, ICSI can be performed immediately using either a cryopreserved and thawed oocyte or a same-day retrieved oocyte; the sperm can also be frozen for future use. In the case of a planned fresh IVF cycle, if sperm retrieval is unsuccessful and the female’s ovarian stimulation has already been completed, oocyte cryopreservation (egg freezing) has been shown to be a viable strategy. In this case, the cryopreserved eggs can be fertilized by donor sperm or by partner sperm if future extractions are successful. A study by Lin et al (2019) included 200 couples with NOA and compared fertilization rates using fresh versus frozen oocytes.^lxii They found that there were no significant differences in fertilization rates using fresh oocytes versus frozen-thawed oocytes (69.2 percent vs. 74.1 percent).

If repeat attempts of sperm retrieval and ICSI are unsuccessful, use of a sperm donor can be considered. A 2020 study by Cai et al tracked females who underwent failed ICSI cycles due to severe male factor infertility, then underwent artificial insemination with donor sperm, either with IVF or intrauterine insemination (IUI). They found that the live birth rate per cycle with donor sperm was 18.9 percent, and that embryological parameters (fertilization, viable cleavage embryos, blastocyst development) were lower with partner sperm and ICSI compared to donor sperm.^lxiii

Conclusion

Sperm retrieval procedures are an important tool in the treatment of male infertility. While there is a range of techniques with varying success rates, the goal is the same: to retrieve sperm from the testicles when it cannot be obtained through a typical ejaculated sample collection. Patients considering sperm retrieval procedures should consult with a fertility specialist to determine which procedure is right for them and to understand the potential risks and benefits. With the help of these procedures, many males struggling with infertility can achieve family building using their own sperm.