History and exam
Key diagnostic factors
common
presence of risk factors
Risk factors include varicocele, cryptorchidism, prior chemotherapy or radiotherapy, current medications, cystic fibrosis and congenital bilateral absence of vas deferens, Y chromosome abnormalities, Klinefelter syndrome (47,XXY), endocrinopathy, and previous infertility.
inability of an opposite-sex couple to conceive
One year of infertility with normal evaluation of the female partner.
vasectomy
An effective form of male contraception that may be able to be surgically reversed.
palpable and dilated testicular veins
Varicocele is the most common identifiable abnormality associated with male infertility.[10] Varicoceles are graded 1+ (palpable with Valsalva); 2+ (palpable); and 3+ (visible through scrotal skin).
uncommon
erectile dysfunction and decreased libido
These may be signs of hypogonadism, which can be of testicular or pituitary-hypothalamic origin.
Psychological stress related to fertility problems may contribute to erectile dysfunction and decreased libido.[2][20] In some severe cases, erectile dysfunction may be a cause of impaired fertility.[20][29]
testis atrophy (testis smaller than 20 cm³)
The volume, size, consistency, and regularity of the testis are key signs of either tumours or arrested spermatogenesis.
body habitus, abnormal hair distribution, and gynaecomastia
May be signs of hypogonadism or chromosomal abnormalities (e.g., XXY).
absent vasa or epididymis
Can be a sign of congenital bilateral absence of vas deferens due to cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation or other unknown embryological abnormality.
Other diagnostic factors
uncommon
headaches, galactorrhoea, and visual disturbance
These may be signs of a pituitary tumour.
anosmia
Suggests Kallmann syndrome (hypogonadotrophic hypogonadism with anosmia) in sexually immature patients.
frequent respiratory infections
May be a sign of immotile cilia syndrome.
pain, blood, or pus with ejaculation
Indications of prostatitis or epididymitis.
Risk factors
strong
varicocele
Dilation of the veins of the pampiniform plexus of the scrotum. They occur commonly on the left side. Many studies support a role for clinically evident varicocele (visible or palpable) in male infertility.[10] The role of subclinical varicocele detected by ultrasonography is controversial. The venous reflux, elevation in testicular temperature, and oxidative stress play an important role in the abnormalities found on semen analysis in patients with varicocele.[10]
cryptorchidism
Cryptorchidism or undescended testis may be associated with oligozoospermia, hypospadias, and testicular cancer.[23]
prior chemotherapy or radiotherapy
Cancer therapy, including radiation or chemotherapy, is often associated with either a transient or a permanent loss of spermatogenesis. Alkylating agents such as cyclophosphamide, chlorambucil, and nitrogen mustard are the most harmful. Studies showed a significant reduction in sperm count associated with radiotherapy in doses ≥50 centigray (cGy).[9]
Patients who receive radiation to the pituitary gland are at risk of developing hypogonadotrophic hypogonadism. Patients scheduled to receive chemotherapy or radiotherapy should be counselled on fertility preservation and sperm banking.[24] Those who undergo chemotherapeutic and/or radiation treatment should prevent pregnancy for at least 12 months after the completion of therapy due to potential genetic damages to sperm.[24]
current medications
Hormone therapy, particularly testosterone supplementation or anabolic steroid treatment, can inhibit spermatogenesis and be detrimental to fertility.
Certain antifungal agents and sulfasalazine can adversely affect spermatogenesis.
Some antipsychotic medications, antidepressants, and antihypertensive agents cause retrograde ejaculation and orgasmic dysfunction.
Long-term opiate use can cause hormonal dysregulation and impair bulk semen parameters.[25] Use of 5-alpha reductase inhibitors can result in sexual dysfunction, and there is mounting evidence of finasteride impairing semen parameters.[25][26]
cystic fibrosis and congenital bilateral absence of vas deferens (CBAVD)
Cystic fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane regulator (CFTR) gene. Men with this condition have atrophic vas deferens. Men with isolated CBAVD with no other clinical signs of CF have a mutation in the CFTR gene in 80% of cases.[9]
Y chromosome abnormalities
Chromosomal abnormalities are more common in with severe oligozoospermia (5%) or azoospermia (10% to 15%).[15] Deletions of several regions of the Y chromosome are associated with male infertility. These regions are called azoospermia factor regions or AZFa, AZFb, and AZFc. These deletions are more likely to be found in men with severe oligozoospermia or azoospermia. The AZFc deletion is the least severe and use of assisted reproductive technology in men with AZFc deletion has a fertilisation rate of around 60% and a live birth rate of around 23%.[27]
Klinefelter syndrome (47,XXY)
One of the most common sex chromosome anomalies. These men have small testes, gynaecomastia, incomplete androgenisation, and infertility due to severe oligozoospermia or complete azoospermia.[16]
endocrinopathy
Several endocrinopathies are associated with low testosterone levels or with decreased follicle-stimulating hormone (FSH) and/or luteinising hormone (LH) secretion or function. These include hyperprolactinaemia, gonadotrophin (FSH or LH) deficiency, or genetic conditions such as Kallmann syndrome (hypogonadism due to a deficiency in gonadotrophin-releasing hormone [GnRH] and associated anosmia).[2] Clinically significant endocrinopathies are found in only 2% of infertile men.[9]
previous infertility
The patient may have previously been in a relationship where children were wanted, but not obtained. Previous miscarriages early in the pregnancy or due to fetal genetic abnormalities may suggest a male factor contribution.
weak
genital tract infection
erectile dysfunction
Multiple psychological, medical, and surgical conditions are associated with erectile dysfunction.[2][19][20] A careful history is a valuable tool in the differential diagnosis of erectile dysfunction.
Psychological stress related to fertility problems may contribute to erectile dysfunction or, in some severe cases, erectile dysfunction may be a cause of impaired fertility.[20][29]
retrograde ejaculation
obesity
Obesity contributes to male infertility.[6] This can be attributed to multiple factors including reduced testosterone levels and increased aromatisation of testosterone to oestrogen. The oestrogen has a negative feedback effect on follicle-stimulating hormone production. Obesity is also associated with erectile dysfunction.[31]
testicular torsion or trauma
May be associated with abnormal semen analysis in 30% to 40% of cases.[17]
lifestyle factors including smoking, alcohol, and cannabis use
Smoking and alcohol have a deleterious effect on semen parameters and sperm viability.[11][12][13][14] There may be a dose-dependent increase in pregnancy loss with paternal smoking.[32]
Marijuana use has been associated with increased risk for abnormal sperm morphology; reporting studies are frequently small and equivocal.[14][22]
exposure to androgen
Men exposed to anabolic androgens or to androgen replacement therapy frequently have low sperm counts or azoospermia. Androgen exposure has a negative feedback effect on follicle-stimulating hormone production and can alter spermatogenesis.
age >55 years
May affect sperm motility.
environmental toxin exposure
Exposure to pesticides or other environmental toxins with oestrogenic activity.[8]
history of coronary artery disease or diabetes mellitus
Cardiovascular disease is frequently associated with erectile dysfunction.[20]
history of STI
STIs can produce scarring and obstruction of the reproductive tract.
hot tub use
Elevation in testicular temperature affects sperm production.
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