Azoospermia
Azoospermia | |
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white blood cells | |
Specialty | Urology |
Azoospermia is the
In a non-pathological context, azoospermia is also the intended result of a vasectomy.[4]
Classification
Azoospermia can be classified into three major types as listed.[3] Many conditions listed may also cause various degrees of oligospermia rather than azoospermia. Pretesticular and testicular azoospermia are known as non-obstructive azoospermia, whereas post-testicular azoospermia is considered obstructive.
Pretesticular
Pretesticular azoospermia is characterized by inadequate stimulation of otherwise normal testicles and genital tract. Typically,
Testicular
Testicular azoospermia means the testes are abnormal, atrophic, or absent, and sperm production severely disturbed to absent. FSH levels tend to be elevated (hypergonadotropic) as the feedback loop is interrupted (lack of feedback inhibition on FSH). The condition is seen in 49–93% of men with azoospermia.[3] Testicular failure includes absence of failure production and low production and maturation arrest during the process of spermatogenesis.
Causes for testicular failure include congenital issues such as in certain genetic conditions (e.g. Klinefelter syndrome), some cases of cryptorchidism or Sertoli cell-only syndrome as well as acquired conditions by infection (orchitis), surgery (trauma, cancer), radiation,[5] or other causes. Mast cells releasing inflammatory mediators appear to directly suppress sperm motility in a potentially reversible manner, and may be a common pathophysiological mechanism for many causes leading to inflammation.[6] Testicular azoospermia is a kind of non-obstructive azoospermia.
Generally, men with unexplained hypergonadotropic azoospermia need to undergo a chromosomal evaluation.
Post-testicular
In post-testicular azoospermia, sperm are produced but not ejaculated, a condition that affects 7–51% of azoospermic men.[3] The main cause is a physical obstruction (obstructive azoospermia) of the post-testicular genital tracts. The most common reason is a vasectomy done to induce contraceptive sterility.[7] Other obstructions can be congenital (for example, agenesis of the vas deferens as seen in certain cases of cystic fibrosis) or acquired, such as ejaculatory duct obstruction for instance by infection.
Ejaculatory disorders include retrograde ejaculation and anejaculation; in these conditions sperm are produced but not expelled.
Unknown
Idiopathic azoospermia is where there is no known cause of the condition. It may be a result of multiple
Genetics
Genetic factors can cause pretesticular, testicular, and post-testicular azoospermia (or oligospermia) and include the following situations:[9] The frequency of chromosomal abnormalities is inversely proportional to the semen count, thus males with azoospermia are at risk to have a 10–15% (other sources citing 15–20% incidence[10]) abnormalities on karyotyping versus about <1 % in the fertile male population.[2]
Pretesticular azoospermia may be caused by congential
Post-testicular azoospermia can be seen with certain point mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene commonly associated with congenital vas deferens abnormalities.[citation needed]
BRD7
BRD7, a transcription regulatory protein, is normally highly expressed in the testis. Absent or reduced expression of BRD7 protein was observed in the testes of azoospermia patients exhibiting spermatogenesis arrest.[11] Homozygous knockout mice [BRD7(-/-)] are infertile and have higher levels of apoptosis and DNA damage in their germline cells.[11]
Gene polymorphisms
The human breast cancer susceptibility gene 2 (
Four genes involved in DNA double-strand break repair and chromosome synapsis (TEX11, TEX15, MLH1 and MLH3) have key roles in genomic integrity, meiotic recombination and gametogenesis. Polymorphisms in these genes were tested for associations with male infertility. Single nucleotide polymorphisms in two of these genes (TEX11 and MLH3) were found to be associated with male infertility involving azoospermy or oligospermia.[13]
Diagnosis
Azoospermia is usually detected in the course of an infertility investigation. It is established on the basis of two semen analysis evaluations done at separate occasions (when the seminal specimen after centrifugation shows no sperm under the microscope) and requires a further work-up.[14]
The investigation includes a history, a physical examination including a thorough evaluation of the scrotum and testes, laboratory tests, and possibly
Low levels of LH and FSH with low or normal testosterone levels are indicative of pretesticular problems, while high levels of gonadotropins indicate testicular problems. However, often this distinction is not clear and the differentiation between obstructive versus non-obstructive azoospermia may require a testicular biopsy.[3] On the other hand, "In azoospermic men with a normal ejaculate volume, FSH serum level greater than two times the upper limit of the normal range is reliably diagnostic of dysfunctional spermatogenesis and, when found, a diagnostic testicular biopsy is usually unnecessary, although no consensus exists in this matter."[14][16][17] Extremely high levels of FSH (>45 ID/mL) have been correlated with successful microdissection testicular sperm extraction.[18]
Serum
Seminal plasma proteins TEX101 and ECM1 were recently proposed for the differential diagnosis of azoospermia forms and subtypes, and for prediction of TESE outcome.[20][21] Mount Sinai Hospital, Canada started clinical trial to test this hypothesis in 2016.[22]
Primary hypopituitarism may be linked to a genetic cause. So a genetic evaluation may be done for men with azoospermia as a result.[2] Azoospermic men with testicular failure are advised to undergo karyotype and Y-micro-deletion testing.[23][9][14]
Treatment
Pre- and post-testicular azoospermia are frequently correctible, while testicular azoospermia is usually permanent.[2] In the former the cause of the azoospermia needs to be considered and it opens up possibilities to manage this situation directly. Thus men with azoospermia due to hyperprolactinemia may resume sperm production after treatment of hyperprolactinemia or men whose sperm production is suppressed by exogenous androgens are expected to produce sperm after cessation of androgen intake. In situations where the testes are normal but unstimulated, gonadotropin therapy can be expected to induce sperm production.
A major advancement in recent years has been the introduction of
In men with post-testicular azoospermia, different approaches are available. For obstructive azoospermia, IVF-ICSI or surgery can be used and individual factors are considered for the choice of treatment.[7] Medication may be helpful for retrograde ejaculation.
See also
References
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- ^ ISBN 978-0-9649702-8-1. Archived (PDF) from the original on 2018-03-26. Retrieved 2010-06-14.)
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- ^ PMID 20202000.
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- ^ ASRM, August 2008. "The management of infertility due to obstructive azzospermia" (PDF). Archived (PDF) from the original on March 4, 2016. Retrieved June 14, 2010.)
{{cite web}}
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- ^ PMID 19421675.
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- ^ PMID 26878912.
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- ^ a b c Esteves SC, Miyaoka R, Agarwal A. An update on the clinical assessment of the infertile male. Clinics (Sao Paulo). [corrected]. 2011;66(4):691–700.
- PMID 25038770.
- ^ Fertil Steril. 2008;90(5 Suppl):S74-7.
- ^ Coburn, M., Wheeler, T., and Lipshultz, L.I. Testicular biopsy. Its use and limitations. Urol Clin North Am. 1987; 14: 551–561.
- ^ Ramasamy R, Lin K, Gosden LV, Rosenwaks Z, Palermo GD, Schlegel PN. High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction. Fertil Steril. 2009;92(2):590-3.
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- ^ "Use of Semen TEX101 to Improve Sperm Retrieval Rates for Men With Non-obstructive Azoospermia". March 8, 2019. Archived from the original on April 13, 2017. Retrieved April 13, 2017 – via clinicaltrials.gov.
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External links
-spermia, Further information: Testicular infertility factors |
Aspermia—lack of semen; anejaculation |
Asthenozoospermia—sperm motility below lower reference limit |
Azoospermia—absence of sperm in the ejaculate |
Hyperspermia—semen volume above upper reference limit |
Hypospermia—semen volume below lower reference limit |
Oligospermia—total sperm count below lower reference limit |
Necrospermia—absence of living sperm in the ejaculate |
Teratospermia—fraction of normally formed sperm below lower reference limit |