HOW TO TREAT 25
ausdoc . com . au 13 SEPTEMBER 2024
HOW TO TREAT 25
Metabolomic fingerprinting can further analyse human seminal plasma and potentially detect any azoospermia changes at the metabolome level . Different metabolite biomarkers can be upregulated or downregulated ( such as arginine , lysine , tyrosine and fructose ) in various abnormal sperm parameters , and these can be detected on nuclear magnetic resonance spectroscopy . 37 While the application of this metabolomics approach appears promising to identify biomarkers relevant for male infertility evaluation , this technology remains largely experimental at this stage . 38
CASE STUDIES
Case study one
IAN , a 32-year-old male , was diagnosed with azoospermia recently during a fertility workup after failing to conceive with his partner , Judy , who is aged 29 . He reports normal sexual function . Ian denies other risk factors for male infertility and is not taking any medications .
Clinical examination shows normal secondary male sexual characteristics . A focused examination of his genitalia reveals normal bilateral testes with the estimated testicular volume of 20cc , but the absence of bilateral vasa . His semen analyses performed on two separate occasions have shown a zero count with low pH ( 6.7 ) and an ejaculate volume of 0.7mL . His hormonal workup reveals normal total testosterone , FSH and LH levels . Genetic testing confirms a normal karyotype with no Y chromosome microdeletion , but a positive CFTR gene mutation . Renal tract imaging studies show an absence of his right kidney and right seminal vesicle in addition to no vas deferens in the scrotum .
The diagnosis of congenital bilateral absence of vas deferens is made . Judy undergoes screening and is ruled out as a carrier of the CFTR variant . They are counselled about the pregnancy rate and genetic risk to any possible offspring . Ian undergoes a successful sperm retrieval procedure with microscopic testicular sperm extraction ( TESE , see figure 12 ) for ICSI / IVF .
Case study two
Greg , a 29-year-old male , has been trying to conceive with his 24-yearold partner , Lin , for the past two years . He recalls normal pubertal development , apart from a history of right orchidopexy for suspected testis torsion at the age of 18 . His other medical history includes ADHD . He is otherwise fit and healthy and does not take any regular medications apart from multivitamins .
Clinical examination shows a tall individual with bilateral gynaecomastia and relatively sparse body hair . Focused examination of Greg ’ s genitalia reveals bilateral small and soft testes with estimated testicular volume of 3cc but normal bilateral epididymis and vasa . His hormonal blood tests show borderline total testosterone of 9nmol / L ( normal 8.7-31nmol / L ), FSH at 14 IU / L ( normal 1.5-12.4 IU / L ), and LH at 11 IU / L ( normal 1.8-8.6 IU / L ). Please note that values may differ between laboratories and will vary with age
His semen analyses done on two separate occasions have shown normal volume azoospermia . Genetic testing confirms 47 , XXY with no Y
Figure 7 . Klinefelter syndrome .
Figure 9 . Presentations of the morphological anomalies of congenital bilateral absence of the vas deferens ( CBAVD ) and congenital unilateral absence of the vas deferens ( CUAVD ). Three presentations of CBAVD and two presentations of CUAVD are morphologically identifiable based on the absences reported by imaging of the vas deferens alone ( indicated in red ). Possible absences of a kidney and / or one or both seminal vesicles are represented by the organs with dotted lines . Other potentially associated anomalies such as absences from the body and / or tail of the epididymis , the ampulla of the vas deferens and the ejaculatory ducts are not taken into account . E = epididymis , K = kidney , T = testis , U = urethra .
chromosome microdeletion or CFTR gene mutation . His scrotal ultrasound shows bilateral small testes measuring 2x2x1cm 3 with the presence of several microlithiases ( see figure 13 ) but no evidence of varicocele .
This is a case of Klinefelter syndrome , and the patient exhibits some features typical of this condition . Greg
Malcolm Gin , Body Morphology Project / CC BY-SA 3.0 / bit . ly / 3WscAfd and bit . ly / 3UOELUu
Bieth E et al . Hum Genet 2021 / CC BY 4.0 / bit . ly / 4bpqxiX undergoes microscopic TESE but no sperm is identified at the time of surgery . The couple elects to use a sperm donor for ICSI / IVF .
CONCLUSION
THE traditional approach in the evaluation of male infertility has primarily been based on conventional semen analysis . However , our
Figure 8 . Anatomy of the adult vas deferens . The proximal part of the vas deferens ( VD , in red ) that follows the epididymis ( E ) is located in the scrotum , easily accessible for palpation . The VD then travels through the inguinal canal and then into the pelvis in a retroperitoneal position . The dilated terminal part of the VD is called the ampulla of the vas deferens . The ejaculatory duct follows the ampulla of the VD with the end of the seminal vesicle and opens in the posterior surface of the prostatic urethra ( U ).
B = bladder , P = prostate , SV = seminal vesicle .
Sperm cells
' Feedback ' hormones
GnRH
Voice breaks Growth of muscle tissue Enlargement of genitalia
Facial , pubic and axillary hair
Testes
Testosterone
increased understanding of genetic testing for male infertility highlights that routine evaluation of semen parameters alone is often insufficient and does not reveal specific information about the cause of male infertility . Detailed genetic studies aid in the development of various state-of-the-art diagnostic tests for male infertility , improve the
LH and FSH
or
Ovaries
Hypothalamus
Pituitary gland
' Feedback ' hormones
Oestrogen
Egg cells
Broadening of hips Menstruation begins Development of breasts Pubic and axillary hair
Figure 10 . Normal hormonal control of puberty from the hypothalamus down to the testes or ovaries and their negative feedback mechanisms . The negative feedback control allows just the right amount of hormone to be released according to the needs of the body at that time . GnRH = gonadotropin-releasing hormone .
Sperm cells
' Feedback ' hormones
GnRH
Voice breaks Growth of muscle tissue Enlargement of genitalia
Facial , pubic and axillary hair
Testes
Testosterone
LH and FSH
or
Ovaries
Hypothalamus
Pituitary gland
' Feedback ' hormones
Oestrogen
Egg cells
Broadening of hips Menstruation begins Development of breasts Pubic and axillary hair
Figure 11 . Flow diagram showing the failure in the hormonal pathway of puberty by the failure of gonadotropin-releasing hormone ( GnRH ) release by the hypothalamus and the subsequent failure of the testes or ovaries to respond correctly .
Bieth E et al . Hum Genet 2021 / CC BY 4.0 / bit . ly / 4bpqxiX Neil Smith / CC BY-SA 3.0 / bit . ly / 3Unu7Ti
Neil Smith / CC BY-SA 3.0 / bit . ly / 3QAD8qT therapeutic strategies to overcome fertility barriers in males undergoing ART , and prevent the transmission of certain genetic conditions to future offspring . To date , there is no single panel of genetic test kits that can analyse all the currently known genetic abnormalities related to male infertility ; clinicians therefore need to exercise sound PAGE 27