Male fertility is a complex and multifactorial phenomenon that relies on various factors, including genetics, environment, and lifestyle. Among the genetic factors that can impact male fertility, chromosomal abnormalities represent a significant contributor. It is known to be the root cause of infertility in 2-14% of males.1 In this blog, we will explore the various genetic disorders that may cause male infertility. But first, let us understand the basics.

What Are Sex Chromosome Abnormalities?

Chromosomes are thread-like structures in cells that contain genetic material (DNA) and determine an individual's physical and biological characteristics.2 Typically, human cells contain a set of 23 chromosome pairs. 22 pairs of these chromosomes, known as autosomes, exhibit no difference for males and females. The remaining 23rd pair, referred to as sex chromosomes, are different in both, where females possess two X chromosomes, while males carry one X and one Y chromosome.3

Chromosomal abnormalities are changes or disruptions in the number or structure of chromosomes.4 Chromosomal defects are more common in infertile men (around 2-14%) than in normal males (around 0.6%).1,5 They can occur spontaneously, or they can be inherited from parents.6

Here Are Some Genetic Disorders That May Cause Male Infertility

Sex chromosomal abnormalities can have a significant impact on male fertility, causing various conditions that affect the production, quality, or function of sperm.7 The abnormalities can disrupt this process, leading to conditions such as Klinefelter syndrome, Turner syndrome, and Y chromosome deletions, among others.

Let’s dive into some of these common genetic conditions that may cause male infertility.

1. Klinefelter’s Syndrome

Klinefelter syndrome is a sex chromosome abnormality that affects males and occurs when a male has an extra X chromosome, resulting in XXY instead of the typical XY chromosome pattern.8 Researchers believe that the characteristics of the condition may be so subtle that it goes undiagnosed until puberty or adulthood, and it's estimated that as many as 75% of men and boys affected by it are never diagnosed.8

This is one of the common genetic disorders that may cause male infertility as it often results in reduced testosterone production, which can lead to smaller testes and reduced sperm production.8 The quality and quantity of sperm may be affected, making it difficult for these individuals to father children naturally. 

However, with advances in assisted reproductive technologies, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), men with Klinefelter syndrome may still have the opportunity to become biological fathers.9 Early diagnosis and management of this condition are crucial for maximizing the chances of successful reproduction and preventing potential complications.8

2. Persistent Mullerian Duct Syndrome

Persistent Mullerian Duct Syndrome (PMDS) is one of the rare genetic disorders that may cause male infertility. This condition occurs when the Mullerian ducts, which are responsible for the development of female reproductive organs, fail to regress in male embryos.10

As a result, affected males may have both male and female reproductive organs, such as testes and a uterus, or only a uterus. The presence of a uterus can lead to the formation of a Mullerian duct cyst, which can cause infertility by obstructing sperm flow or impairing sperm function.10

Additionally, the presence of female reproductive organs can result in hormonal imbalances, which may further affect fertility. The severity of PMDS can vary, with some individuals being asymptomatic and others requiring surgical intervention to remove the uterus or cysts.10 Men with PMDS may also benefit from assisted reproductive technologies, such as sperm retrieval or sperm donation, to achieve parenthood.

3. Adrenal Insufficiency

Adrenal insufficiency is a medical condition that occurs when the adrenal glands, located above the kidneys, fail to produce enough cortisol and aldosterone hormones.11 These hormones are essential for the proper functioning of the male reproductive system, including the production of sperm.

Inadequate levels of cortisol can lead to a decrease in testosterone production, which is necessary for the development and maturation of sperm.12 This can cause a reduction in sperm count, quality, and motility, which can ultimately lead to male infertility.

Additionally, adrenal insufficiency is one of those genetic disorders that may cause male infertility by affecting libido and sexual function.12

4. Cryptorchidism

Cryptorchidism, also known as undescended testes, is a common condition that occurs when one or both testes fail to descend into the scrotum during fetal development.13 This condition affects male fertility as the testes require a lower temperature than the rest of the body to produce healthy sperm. Failure to descend can cause the testes to remain at a higher temperature, which may result in reduced sperm production, poor sperm quality, or impaired sperm function.

In addition, cryptorchidism may increase the risk of testicular cancer and torsion, which can further affect fertility.13 Treatment for cryptorchidism typically involves a surgical intervention to bring the testes into the scrotum.13

5. Congenital Adrenal Hypoplasia

Congenital Adrenal Hypoplasia (CAH) is last on the list of common genetic disorders that may cause male infertility. It is a rare condition that affects the development of the adrenal glands. This condition can have a significant impact on male fertility as the adrenal glands produce hormones that are essential for the development and function of the testes.14

In males with CAH, the adrenal glands do not produce enough hormones, which can result in underdeveloped testes, reduced sperm production, or impaired sperm function.14 Moreover, CAH can lead to other health complications, such as low blood pressure, low blood sugar, and dehydration, which can further affect fertility.14

Treatment for CAH typically involves hormone replacement therapy to replace the missing hormones and correct any hormonal imbalances.15 However, the effects of CAH on fertility can be irreversible if left untreated or if treatment is delayed. Therefore, early diagnosis and management of CAH are critical for preserving male fertility and preventing potential complications.

Wrapping Up

In conclusion, chromosomal abnormalities can have a serious effect on male fertility, causing various conditions that affect the production, quality, or function of sperm. Klinefelter syndrome, Y chromosome deletions, Persistent Mullerian Duct Syndrome, Cryptorchidism, and Congenital Adrenal Hypoplasia are just a few examples of genetic disorders that may cause male infertility. These conditions can make it difficult for affected men to father children naturally. Early diagnosis and management of these conditions are crucial for maximizing the chances of successful reproduction and preventing potential complications. 

LifeCell offers an extensive at-home genetic test - InferGenes Male to find the root cause of male infertility. The test can detect chromosomal abnormalities responsible for the above-mentioned conditions as well as other male health conditions. Our panel analyzes 36 definitive clinically relevant genes through advanced Next generation sequencing technology and provides accurate results within 21 days.  Men who are struggling with infertility can take this test after seeking the advice of a qualified healthcare professional to evaluate their fertility and explore potential treatment options.

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