What diseases and disorders are the causes of male infertility?

By (gynecologist), (embryologist), (gynecologist), (embryologist) and (biochemist).
Last Update: 07/26/2022

Infertility is defined as difficulty in achieving pregnancy when a couple has been having regular unprotected sexual intercourse for one year. In actuality, infertility affects 1 in 6 couples of childbearing age.

Reasons for infertility can be broken down into 30% being due to for male causes, 30% being to female causes and 20% due to causes involving both partners. Moreover, the remaining 20% of infertility cases are due to an idiopathic cause, where the reason for the couple not getting pregant is not known.

We can classify male infertility into different groups according to the origin. These being pretesticular, testicular, posttesticular and spermatic.

Provided below is an index with the 8 points we are going to expand on in this article.

Pretesticular origin

One possible cause of male infertility is the pretesticular factor due to problems in the endocrine system. For correct sperm production to occur, the brain must send the necessary endocrine signals which coordinate the whole process. If this communication fails in some way, the male will be sterile.

To follow, we discuss the most common disorders that we consider to be pretesticular factors for male infertility.

Hyperprolactinemia

This is a disorder caused by increased levels of the hormone prolactin in the blood. Produced by the pituitary gland, prolactin is responsible for the production of breast milk and influences levels of sex hormones.

Prolactin and the hormones that produce sperm (gonadotropins) must be in balance. When prolactin is high, FSH and LH production is decreased and this affects spermatogenesis (sperm formation).

Therefore, elevated prolactin levels in the male may cause:

  • Oligospermia, a low concentration of spermatozoa in the semen.
  • Erectile dysfunction.
  • Low libido.

It is worth mentioning that there are pharmacological treatments that can reduce prolactin levels. However, most cases of hyperprolactinemia are the result of other more serious pathologies.

Thyroid problems

The thyroid gland is responsible for regulating metabolic processes including oxygen consumption, protein production and hormone sensitization. If this gland is not functioning as is should, it can trigger the two following pathologies:

Hyperthyroidism
excessive production of the hormone thyroxine. Most men suffering from hyperthyroidism have abnormal sperm morphology, which impairs their fertility.
Hypothyroidism
insufficient production of thyroid hormones. In these cases, men with hypothyroidism may experience decreased libido, reduced sperm quality and quantity.

In any case, it is important to pay attention to the signs and symptoms that of hypothyroidism and hyperthyroidism and to consult an endocrinologist if in doubt. An endocrinologist will be able to determine the cause and provide possible solutions.

Diabetes and male infertility

Diabetes is an endocrinological disease characterized by high blood sugar levels.

A man who is diagnosed with diabetes which is not controlled may present with testicular damage, decreased sperm quality and quantity, ejaculation disorders and erectile dysfunction. All of these being factors that cause infertility in men.

Diabetes increases DNA damage in the sperm, resulting in a lower conception rate and an increase in poor quality embryos.

Hypergonadotropic hypogonadism

This type of hypogonadism, also called primary hypogonadism, is due to a problem in the Leydig cells. The problem lies when these cells are not able to produce enough testosterone and, therefore, sperm are not generated correctly. The following are the main factors that cause hypergonadotropic hypogonadism:

  • Genetic abnormalities, such as Klinefelter's syndrome
  • Systemic diseases.
  • Infectious diseases.
  • Testicular failure.

Furthermore, men with hypergonadotropic hypogonadism may have a low sperm count or even complete absence of sperm in the ejaculate.

Hypogonadotropic hypogonadism

This is a pathology caused by insufficient production of the hormones responsible for the formation of spermatozoa. Hypogonadotropic hypogonadism is a result of a malfunction of the pituitary gland and hypothalamus.

There is a hormonal hierarchy that begins in the hypothalamus, which sends signals to the pituitary gland. The pituitary processes these signals and then sends more to the testicles, controlling sperm production. If this hierarchy is not functioning correctly in the man, it can cause male infertility.

In addition, there is an inherited disorder called Kallmann's syndrome that is falls under hypogonadotropic hypogonadism.

Testicular origin

The formation of spermatozoa consists of several stages. During these stages, the genetic material divides and the cells develop and are modified until they become spermatozoa.

Male infertility of testicular origin refers to factors that mainly affect the testicles, causing difficulty in achieving a natural pregnancy.

Microdeletions of the Y chromosome

The Y chromosome is the male sex chromosome. It is the smallest chromosome of all and contains the genes responsible for the formation of the testes located in the chromosomal region called AZF.

When a man presents any modifications or damage in this region, he will suffer a severe male factor which could be:

  • Oligozoospermia, low amount of spermatozoa in the ejaculate.
  • Azoospermia, the total absence of spermatozoa in the semen.

In the event that men with AZF defects were to have children, the probability of inheriting the genetic defects on the Y chromosome would be high.

Klinefelter syndrome

Klinefelter syndrome is a chromosomal disorder in which the male has an extra X chromosome. The normal male karyotype is 46, XY. However, a male with Klinefelter syndrome will have a 47, XXY karyotype. This causes a lower concentration of testosterone, impeding sperm production.

One possible treatment is to use a testosterone replacement drug so the man can develop secondary sexual characteristics and avoid furture problems. However, testosterone administration does not solve infertility issues.

Noonan syndrome

The genetic disease known as Noonan syndrome is caused by a mutation in chromosome 12. Boys with this genetic disorder suffer from abnormal development and often show penile defects and/or cryptorchidism. As a result, most men born with Noonan syndrome have fertility problems and will find it difficult to father a pregnancy.

Cryptorchidism

Cryptorchidism is a birth defect (congenital) in which one or both testicles do not descend into the scrotal sac. In these cases, surgery is required at an early age to descend the testicles, otherwise the male will having problems in the sperm formation.

Undescended testicles are usually located in the groin area, although they can also be found at any point along their trajectory towards the scrotum.

If you would like to learn more about this topic, we encourage you to visit the following article: Cryptorchidism: a testicular disorder that causes sterility.

Varicocele

This condition is caused by inflammation of the blood vessels that supply the spermatic cord and transport the blood from the testicles. The veins dilate and blood pools, causing the testicular temperature to rise, in turn affecting sperm formation.

Normally, varicocele does not cause serious symptoms, but the man may experience pain or even have trouble conceiving. Surgical treatment of varicocele allows the male to recover his fertility. For more information on this topic, you can continue reading here:

Orchitis

Testicular orchitis is defined as inflammation of one or both testicles due to an infection caused by bacteria or viruses. It can also originate from unknown causes. However, most cases of hyperprolactinemia are the result of an episode of mumps.

Inflammation of the testicles leads to an elevation of the temperature in the testicular area, which hinders spermatogenesis. Therefore, orchitis may be a factor in male infertility.

Hydrocele

The testicles are surrounded by a fluid that makes them less vulnerable to knocks. The blockage of a blood vessel or lymphatic vessel may result in an increase of fluid in the testicles.

Although fluid accumulation by itself does not affect male fertility, it may be a symptom of other factors that do. Therefore, it is not a direct cause of infertility in men.

Testicular Hypoplasia

Testicular hypoplasia, also called scrotal hypoplasia, is a congenital disorder characterized by abnormal development of the testicles in males. The testicles do not form correctly and are smaller than they should be.

The diagnosis of this condition is usually made at puberty, when their size becomes apparent.

XY gonadal dysgenesis

XY gonadal dysgenesis, also called Swyer syndrome, is a genetic disorder of sexual development characterized by the lack of agreement between sexual phenotype and genotype. Individuals with this genetic disease have a typically male karyotype (46, XY), although physically they have female characteristics.

The etiology of XY gonadal dysgenesis is associated with a mutation in the SRY gene of the Y chromosome, which blocks the development of the testes.

If you are interested in learning more about this syndrome, we recommend visiting the following link: Swyer syndrome: causes, clinical manifestations and pregnancy.

Post testicular origins

The spermatazoa formed in the testicle must undergo maturation to be able to fertilize the egg. This maturation begins in the testis, and continues in the female reproductive tract, in a process called sperm capacitation.

Male sterilty of a post testicular origen includes all the factors that affect the sperm once they have been formed in the testes. In the following section we discuss the main reasons for post-testicular factor infertility.

Sperm duct obstruction

The ejaculatory ducts are the structures of the male anatomy through which the sperm exit the testicles on their journey to the exterior. The sperm pathways include the epididymis, vas deferens and urethra. Any deformation in these spermatic pathways causes an obstruction of the passage of spermatozoa. For this reason, it is a factor of infertility for men.

In addition, cystic fibrosis is a genetic alteration that causes a total absence of spermatozoa in the ejaculate due to an obstruction of the vas deferens, the tubes responsible for carrying semen from the testicle to the penis.

Finally, it should be noted that vasectomy is the most common cause of sperm duct blockage.

Immunological infertility

Immunological male infertility is due to the presence of antispermatozoa antibody (ASA) in the ejaculate. These ASA antibodies can interfere with fertilization at various, making it difficult for the egg to meet the sperm.

Anti-sperm antibodies can be found in the sperm itself, in seminal plasma or even in cervical mucus.

Retrograde Ejaculation

Retrograde ejaculation occurs when semen flows back into the bladder instead of out because the sphincter at the neck of the bladder fails to close. It is an defect that does not allow natural pregnancy, although it is easily solvable.

The causes of retrograde ejaculation are multiple, such as diabetes, drugs and surgeries of the prostate, gallbladder or urethra.

 

If you would like to read more about this, please take a look at this article: What is retrograde ejaculation?

Erectile dysfunction.

Sexual impotence, also known as erectile dysfunction, refers to a man's inability to keep his penis erect long enough to achieve ejaculation. It is a benign disease with multiple causes: psychological, hormonal, basal and nervous.

When a man suffers from erectile dysfunction he cannot have full sexual intercourse, so the possibility of pregnancy will be nil.

Hypospadias

This condition consists of a congenital defect where the opening of the urethra is not at the tip of the penis, but located in a different part of the penile shaft or even in the testicles. Mild hypospadias does not interfere in achieving pregnancy, but in the case of severe hypospadias it can be impossible to deposit semen in the vagina.

Sperm Factor

Male infertility due to spermatic origin is the most common and is caused by an alteration in the quality of the man's semen. The different problems causing infertility due a sperm factor are easy to determine by means of a semen analysis.

Each of the possible alterations in semen is described below:

Oligozoospermia
seminal alteration characterized by a sperm concentration lower than 15 million/mL.
Cryptozoospermia
when the sperm concentration is less than 100,000 spermatozoa.
Astenozoospermia
sperm motility disorder. If the percentage of immotile sperm is high, it complicates the possibility of achieving pregnancy. In these situations it would be necessary to resort to an assisted reproduction technique.
Teratozoospermia
this is a high percentage of spermatozoa with abnormal morphology. According to the World Health Organization (WHO), a man should have at least 4% of sperm with normal morphology.
Necrozoospermia
high number of dead spermatozoa.
Azoospermia
total absence of spermatozoa in the ejaculate.

If you want to learn more about them, we encourage you visit the following article: Male infertility due to sperm factor: causes and treatments[ cajainfo n="8"] [faq-questions] [faq-questions]

Assisted procreation, as any other medical treatment, requires that you rely on the professionalism of the doctors and staff of the clinic you choose. Obviously, each clinic is different. Get now your Fertility Report, which will select several clinics for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

FAQs from users

What is the main reason for male infertility?

By Blanca Paraíso M.D., Ph.D., M.Sc. (gynecologist).

The most frequent cause of male infertility is a defect in sperm production (spermatogenesis), resulting in seminograms with low sperm count or low sperm motility. This is the problem in 65-80% of men who present with difficulties in achieving pregnancy.
Read more

Is pregnancy possible with retrograde ejaculation?

By Sergio Rogel Cayetano M.D. (gynecologist).

The answer is yes.

When a man suffers from retrograde ejaculation, there is a failure that causes semen to exit the urethra and not enter the bladder. Therefore, these men will be able to achieve orgasm without any problem, but some or usually all of their sperm, will not come out, so the main symptom is orgasm without ejaculation.

In these situations it will be necessary to resort to assisted reproduction techniques to achieve pregnancy.
Read more

Is male fertility affected in men with only one testicle?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

Possessing a single testicle, either from birth or due to a later occurence such as cancer, does not imply that there is a fertility problem. If the remaining testicle works correctly and the spermatogenesis is not affected, the man will be able to father a natural pregnancy without any problem.

Can hypothyroidism cause sterility in men?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

Hypothyroidism or thyroid problems can be a cause of infertility in men, since it causes alterations in the sperm maturation process due to problems in the metabolic processes involved. For this reason, it is advisable to carry out an endocrine study.

We have talked about Klinefelter syndrome as a disease that causes infertility in men. If you want to more information we recommend accessing the following article: Klinefelter syndrome: symptoms característicos y treatment.

When a man suffers from a post-testicular disorder, his fertility may also be compromised. You can get more detailed information about these disorders in this article: Male infertility due to a post-testicular factor.

We make a great effort to provide you with the highest quality information.

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References

Devoto E, Madariaga M, Lioi X. Causes of male infertility. The contribution of the endocrine factor. Rev Med Chil. 2000 Feb;128(2):184-92.

Jedidi I, Ouchari M, Yin Q. Sex chromosomes-linked single-gene disorders involved in human infertility. Eur J Med Genet. 2019 Sep;62(9):103560. doi: 10.1016/j.ejmg.2018.10.012.

Juárez de Diego JF (1999). Principales causas de infertilidad masculina. En: Arrondo JL. Actualización en Andrología. Publimed Comunicación SL. Pamplona.

Krausz C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25(2):271-85.

Sironen A, Shoemark A, Patel M, Loebinger MR, Mitchison HM. Sperm defects in primary ciliary dyskinesia and related causes of male infertility. Cell Mol Life Sci. 2019 Nov 28. doi: 10.1007/s00018-019-03389-7.

Sociedad Española de Fertilidad (SEF) (2011). Manual de Andrología. Coordinador: Mario Brassesco. EdikaMed, S.L. ISBN: 978-84-7877.

FAQs from users: 'What is the main reason for male infertility?', 'Is pregnancy possible with retrograde ejaculation?', 'Is male fertility affected in men with only one testicle?' and 'Can hypothyroidism cause sterility in men?'.

Read more

Authors and contributors

 Blanca Paraíso
Blanca Paraíso
M.D., Ph.D., M.Sc.
Gynecologist
Bachelor's Degree in Medicine and Ph.D from the Complutense University of Madrid (UCM). Postgraduate Course in Statistics of Health Sciences. Doctor specialized in Obstetrics & Gynecology, and Assisted Procreation. More information about Blanca Paraíso
License: 454505579
 Marta Barranquero Gómez
Marta Barranquero Gómez
B.Sc., M.Sc.
Embryologist
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV
 Sergio Rogel Cayetano
Sergio Rogel Cayetano
M.D.
Gynecologist
Bachelor's Degree in Medicine from the Miguel Hernández University of Elche. Specialist in Obstetrics & Gynecology via M. I. R. at Hospital General de Alicante. He become an expert in Reproductive Medicine by working at different clinics of Alicante and Murcia, in Spain, until he joined the medical team of IVF Spain back in 2011. More information about Sergio Rogel Cayetano
License: 03-0309100
 Zaira Salvador
Zaira Salvador
B.Sc., M.Sc.
Embryologist
Bachelor's Degree in Biotechnology from the Technical University of Valencia (UPV). Biotechnology Degree from the National University of Ireland en Galway (NUIG) and embryologist specializing in Assisted Reproduction, with a Master's Degree in Biotechnology of Human Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI) More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Michelle Lorraine Embleton
Michelle Lorraine Embleton
B.Sc. Ph.D.
Biochemist
PhD in Biochemistry, University of Bristol, UK, specialising in DNA : protein intereactions. BSc honours degree in Molecular Biology, Univerisity of Bristol. Translation and editing of scientific and medical literature.
More information about Michelle Lorraine Embleton

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