When is sperm retrieval recommended?

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Sperm aspiration is a procedure used to retrieve sperm directly from the testicles or epididymis when it is not possible to obtain sperm through ejaculation.  

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Sperm samples for IVF are typically obtained via ejaculation and collection of the semen sample (the sperm is inside the semen) in a container. However, sometimes obtaining sperm via ejaculation is not possible or a semen sample does not contain enough sperm - in these cases sperm needs to be retrieved surgically.  

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The following conditions are indications for surgical sperm retrieval:

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• Obstructive azoospermia (OA): This describes a blockage (obstruction) within the male reproductive tract, which leads to a complete absence of sperm within the ejaculate (azoospermia).^i,ii    There are various causes for this. It can be congenital (meaning occurring from the time of birth), such as in the case of congenital absence of the vas deferens, or an obstruction with no known cause. It can also be acquired (meaning it occurs after birth), which can be a result of trauma, infection, or a previous vasectomy, among other causes.ⁱⁱⁱ
• Non-obstructive azoospermia (NOA): This describes the inability of the testes to adequately produce sperm, which also means there will be no sperm within the ejaculate. It can be due to either primary hypogonadism or secondary hypogonadism.^iv,v Primary hypogonadism occurs due to an abnormality of testicular function that impairs sperm production. Secondary hypogonadism results from impaired hormone release from the pituitary gland or hypothalamus (both are hormone-producing glands within the brain).^vi  
• Abnormal sperm development: In the case that sperm are viable, but unable to move (non-motile), sperm retrieval is sometimes required for fertilization to occur via IVF.^vii,viii
• Ejaculatory dysfunction: In this case, other treatments are typically attempted prior to proceeding with sperm retrieval. Medications, urinary sperm retrieval, prostatic massage, penile vibratory stimulation, and electroejaculation may be attempted first. If these are unsuccessful, surgical sperm retrieval can be used.^ix
• Anejaculation: This occurs when there is no semen expelled during the ejaculatory process. There are multiple causes for this including obstruction of the ducts that produce semen, trauma, injury during surgery, and radiation. It can also be caused by problems with the nervous system, including Parkinson’s disease, multiple sclerosis, and spinal cord injuries.^x
• Retrograde ejaculation: This occurs when semen is not expelled out of the urethra, but rather flows backward into the bladder during ejaculation due to impaired contraction of the muscles of the bladder neck. This can occur as a side effect from medications or procedures that result in the relaxation of the bladder neck, which normally contracts to prevent retrograde ejaculation. Retrograde ejaculation can also occur in patients with diabetes or for unexplained reasons.^xi

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What types of sperm retrieval procedures are available?‍

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The main types of sperm retrieval procedures available include testicular sperm aspiration (TESA), percutaneous epididymal sperm aspiration (PESA), testicular sperm extraction (TESE), and a subset of TESE known as microscopic testicular sperm extraction (microTESE). All these procedures are methods for retrieval of sperm, and further information about each procedure is detailed below.  

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Following sperm retrieval, the sperm can be used to fertilize the female’s eggs using in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). Because there are lower numbers of sperm available compared to typical ejaculated semen samples, ICSI is used instead of traditional IVF – this means that the embryologist will select a sperm to inject directly into the mature oocyte. Sperm retrieved via aspiration or extraction cannot be used for either intrauterine or at home insemination because the sperm are either non-motile or not fully motile and not numerous enough for these methods to be successful.  

What is TESA? 

Testicular sperm aspiration (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 and aspirating the contents into a syringe. The fluid that is aspirated typically contains components of seminiferous tubules, as well as sperm. The contents are then inspected for sperm under a microscope.^xii  

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

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• Advantages: It is a simple procedure to complete, and therefore does not require more advanced training or equipment compared to other techniques. It can be completed under local anesthesia.^xiv  Because TESA removes components of the seminiferous tubules, as well as 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).^xv
• Disadvantages: Because it is completed “blindly” and by moving the needle in different directions, the clinician does not know for certain which structures are being punctured by the needle during a TESA. This increases the risk of testicular damage and can lead to bleeding or hematoma formation following the procedure.^xvi,^xvii Furthermore, TESA may be less successful in some situations (particularly in the case of non-obstructive azoospermia) than testicular sperm extraction (TESE) or microTESE, which are described below.^xviii This is because the samples are taken blindly, and less tissue is removed with the needle than by removing pieces of tissue from the testicle.

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What is PESA? 

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Percutaneous epididymal sperm aspiration (PESA) also involves aspirating fluid from the epididymis using a specialized needle. It differs from TESA because the aspiration needle is inserted into the epididymis instead of the testes in order to retrieve the sperm. During PESA, the head of the epididymis (which is situated at the top of the testes) is located by palpation. A needle is advanced through the epididymal ductule while applying suction, and fluid is aspirated into a syringe. The fluid is then examined under a 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.^xix PESA is indicated for obstructive azoospermia, but it is not performed.^xx

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• 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. ^xxi
• Disadvantages: During PESA, the epididymal ductule is located by palpation alone, and therefore the ductule may be missed during an attempt. Similar to TESA, there is a chance of puncturing a blood vessel leading to bleeding during the procedure. Finally, it can only be used for patients with obstructive azoospermia and has a lower retrieval rate than testicular sperm extraction in some cases.^xxii  

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What is TESE? 

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Testicular sperm extraction (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 microscope. ^{xxiii, xxiv}

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During the conventional open TESE procedure, a small incision is made through the skin of the scrotum, the underlying muscle layer, and outer covering of the testes. ^{xxv, xxvi} Small samples of the testicular parenchyma are obtained, and the layers of the outer coverings are sutured back together. The specimen is then immediately examined under a microscope for the presence of sperm, and for diagnostic clarification.^{xxvii, xxviii} Sometimes the samples are evaluated as the procedure is taking place so that additional samples can be taken if few or no sperm have been found. Other times, the samples are sent to the andrology lab and evaluated immediately after the procedure. Depending on the clinical context, either a single incision or multiple incisions are made in the testicle through which multiple biopsies can be taken.^{xxix, xxx}

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• Advantages: Can be performed using local anesthesia, often combined with intravenous sedation or epidural anesthesia.^xxxi TESE is considered more effective than aspiration techniques for NOA and can help with diagnosis of the underlying causes of azoospermia.^{xxxii, xxxiii} As this is not a blind technique, 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 always resolves on its own.^xxxiv Pain, swelling, and potential for infection are also potential risks. In some cases of TESE, a larger volume of testicular tissue is removed to obtain sperm which may lead to reduced blood flow and tissue in the testes (devascularization), and lower testosterone levels.^{xxxv, xxxvi, xxxvii, xxxviii}

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A more advanced form of TESE, known as 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 studied intraoperatively for the presence of sperm. If no sperm is present, the same procedure can then be completed on the other side. The layers of the testes and scrotum are then sutured closed.^xxxix

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Many providers consider MicroTESE to be the gold standard procedure for sperm retrieval in patients with non-obstructive azoospermia^xl because in these patients, spermatogenesis often only occurs in small healthy segments of the testes, which are best identified microscopically.^xli

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Other sperm retrieval techniques 

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

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• Penile vibratory stimulation (PVS): During PVS, a vibrating device is placed against the glans penis to stimulate ejaculation. Once ejaculation occurs, the semen is collected. In individuals who are anejaculatory due to a spinal cord injury affecting the higher part of the spine, PVS is the most effective method at obtaining the highest total motile sperm yield. It is often preferred as it is less invasive compared to electroejaculation (EEJ). However, PVS may not be as effective for individuals with a lower spinal cord injury.^xlii
• This is generally a safe, non-invasive procedure. There is a risk of causing irritation to the skin of the glans penis.  
• In individuals with an SCI above the level of T6 (a higher SCI), there is a risk of autonomic dysreflexia. This is a severe reflex response which causes the blood pressure to rise rapidly. Those at risk are typically treated with a medication to lower blood pressure before the procedure, and by measuring the blood pressure sequentially during PVS.^xliii
• Electroejaculation (EEJ): During EEJ, a probe is placed in the rectum. Electrical stimulation is delivered transrectally, which induces ejaculation by activating the pelvic muscles.^xliv Sometimes with EEJ, retrograde ejaculation will occur in the bladder. If this occurs, sperm must subsequently be retrieved from the urine. EEJ is effective at nearly all levels of spinal cord injury.^xlv
• Like PVS, there is a risk of autonomic dysreflexia in those with SCIs above T6. Therefore, these patients should be given medication to lower blood pressure prior to EEJ. Electroejaculation is completed under general anesthesia in patients that have a neurological injury but still have pelvic sensation, to prevent pain during the procedure.^xlvi
• Prostatic massage: Prostatic massage can be performed by a physician inserting a finger into the rectum and massaging the prostate and seminal vesicles to push out semen. While this is inexpensive and does not require specialized equipment, it is less effective at obtaining sperm.^xlvii

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How successful are sperm retrieval procedures? 

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Success rates for sperm retrieval procedures can vary depending on the specific method used and the patient's individual circumstances. For example, success rates can be impacted by the underlying cause of male infertility, the age of the patient, and the experience and skill of the healthcare provider performing the procedure. Additionally, the success of the procedure may be impacted by the timing and frequency of the procedure, as well as the use of other fertility treatments in conjunction with the sperm retrieval procedure. Overall, the success rates of these procedures can vary widely and should be evaluated on a case-by-case basis, but they are discussed generally below:

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Testicular sperm aspiration (TESA)

TESA has been shown to be effective for men with asthenozoospermia (decreased sperm motility). In a study of 28 men with severe asthenozoospermia (progressive motility ≤ 1 percent), they found that the sperm retrieval rate (SRR) was 100 percent, and sperm was retrieved from one of the testes only.^xlviii

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TESA has also been shown to be very effective in men with obstructive azoospermia (OA), though is less effective in non-obstructive azoospermia (NOA). A study by Jensen et al (2016) found the SRR to be 100 percent in men with OA (82/82 men), compared to an SRR of 30 percent in men with NOA (38/125 men).^xlix

Percutaneous epididymal sperm aspiration (PESA)

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

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PESA is not performed for individuals with non-obstructive azoospermia.^li

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Testicular sperm extraction (TESE) and microTESE

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. They found that the SRR with conventional TESE ranged between 17-45 percent, and from 42.9-63 percent in the microTESE group.^lii

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For men with NOA, a study by Zhang et al (2021) found that microTESE overall had a 46.0 percent sperm retrieval rate.^liii They found the following sperm retrieval rates for the corresponding conditions causing non-obstructive azoospermia (NOA):^liv

• Klinefelter syndrome: SRR 44.7 percent  
• AZFc microdeletion: SRR 73.6 percent
• Cryptorchidism: SRR 75.0 percent
• Previous mumps and bilateral orchitis: 100.0 percent
• Idiopathic NOA: 30.7 percent

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TESA vs. conventional TESE vs. microTESE:

To date, there is a general lack of consensus on the best sperm extraction technique to treat non-obstructive azoospermia, due to heterogenous results and lack of randomized controlled trials. ^{lv, lvi, lvii} A systematic review and meta-analysis by Bernie et al (2015) compared the SRR in men with NOA undergoing TESA, conventional TESE, or microTESE. 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).^lviii  

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Other Non-Surgical Techniques:

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

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

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Electroejaculation (EEJ) can be highly effective at sperm retrieval for those with neurogenic anejaculation. A study by Giulini et al (2004) found that in men with infertility secondary to SCI, 32/34 men (94.1 percent) were able to achieve ejaculation with EEJ.^lx In other studies, it has been stated to be almost 100 percent effective.^lxi

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Prostatic massage is less consistently effective at retrieving sperm from men with SCI. They found sperm was successfully retrieved in only 22/69 men (32 percent) in the study.^lxii

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What happens after sperm retrieval?

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

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There is evidence to indicate that it is worthwhile repeating microTESE in men with NOA who underwent a previous unsuccessful microTESE. Ozman et al (2021) found that 18.4 percent of men with NOA and a previous unsuccessful microTESE had a successful sperm retrieval on repeat attempt.^lxiv

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After sperm are retrieved via one of the above methods, ICSI can be performed immediately using cryopreserved and thawed or same-day retrieved oocytes, or the sperm can be frozen for future use. In the case of a planned fresh cycle, if sperm retrieval is unsuccessful and ovarian stimulation has already been complete, 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) studied 200 couples with NOA and compared the fertilization rates using fresh vs. frozen oocytes. They found that there were no significant differences in fertilization rates using fresh oocytes versus frozen-thawed oocytes (69.2 vs 74.1 percent,). ^lxv

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If repeat attempts of sperm retrieval and ICSI are unsuccessful, sperm donation can be considered for severe male factor infertility. A study of women who underwent failed ICSI cycles due to severe male factor infertility then underwent artificial insemination with donor sperm, either with in-vitro fertilization (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 with donor sperm.^lxvi

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Conclusion

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In conclusion, sperm retrieval procedures are an important tool in the treatment of male infertility. While there are different types of procedures with varying success rates, the goal is the same: to retrieve sperm from the testicles when it cannot be obtained through 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 men struggling with infertility can achieve family building using their own sperm.  

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