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Reproduction and Fertility > Male Infertility > Flashcards

Male Infertility Flashcards

1
Q
  1. Define infertility
    How many people have difficulty conceiving?
    Difference between primary and secondary infertility?
A
  • an inability to conceive after 12 months or more of unprotected sexual intercourse (WHO 2009)
  • 1 in 7 couples have difficulty conceiving which approximates to around 3.5million people in the UK
  • Primary is couples who have never conceived and secondary is couples who have previously conceived (NICE 2013)
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2
Q
  1. What proportion are attributable to male factors?
A
  • Factors causing infertility are attributable to both male and female with approximately 1/3 of infertility related to each gender (Centres for Disease Control and Prevention, 2009)
  • Idiopathic in 25% of cases
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3
Q
  1. Aetiology of male infertility
A
  • The most common cause of male infertility is due to a varicocele 40%, which will be discussed in more detail further into the essay
  • Other aetiologies include infection, genetics, obstruction and endocrine problems
  • A large proportion of cases are idiopathic in nature - 25%
  • All these problems have a direct result on the sperm number, morphology of function and thus affect fertility (Greenberg et al., 1978)
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4
Q
  1. What is a varicocele?
    What percentage of infertile men have this?
    What type of infertility is it?
A
  • Dilation of pampiniform venous plexus above and around the testes
  • 25% of infertile men have this form of nonobstructive azoospermia
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5
Q
  1. What is the mechanism of varicocele infertility?
A
  • Increased oxidative stress, decreased antioxidant capacity

- Leads to DNA fragmentation and spermatozoa fail to fertilise egg

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6
Q
  1. Evidence for DNA fragmentation in varicocele
A
  • Cortes-Gutierrez et al., 2016
  • the frequency of sperm cells with fragmented DNA was studied in a group of 20 infertile patients with varicocele and compared with 20 fertile males
  • DNA breakage detection-FISH, patients with varicocele showed 25.54% of spermatozoa with fragmented DNA, significantly higher than those of the group of fertile subjects
  • NO and peroxynitrite, a potent oxidant ROS, have alrewady been demonstrated to be produced in high concentrations in the dilated spermatic veins. Thus, they could be main contributors to the high OS level in varicocele, supporting the theory of increased DNA fragmentation (Romeo et al., 2001)
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7
Q
  1. Diagnosis of varicocele

What physical examination would you do?

A
  • Physical exam – palpation of the scrotum during upright Valsalva manoeuvre (WHO)
  • A normal semen analysis excludes varicocele infertility as usually decreased conc and teratospermia
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8
Q
  1. What is the treatment for varicocele?

When is ICSI used?

A
  • Surgery is an option to remove the varicocele, whilst another is the ART which requires testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI)
  • ICSI is ART – used in severe infertility – when sperm motility, morphology and count low
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9
Q
  1. Describe ICSI
A
  • Harvest oocytes and placed in medium, sperm extracted and single placed in oocyte cytoplasm, incubated and fertilised egg placed into female
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10
Q
  1. Evidence for varicocelectomy on improving fertility by increasing sperm retrieval
A
  • Schlegel & Kaufmann, 2004
  • Retrospective study of effect of varicocelectomy on sperm retrieval rates for men and the need for TESE
  • 22% had sperm reported on at least one semen analysis postoperatively. However, only 9.6% of men after varicocele repair had adequate motile sperm in the ejaculate for ICSI, without TESE.
  • The benefits of varicocelectomy in men with nonobstructive azoospermia may be less than previously reported which considered success to be the presence of sperm on any semen analysis after varicocelectomy.
  • Therefore the more clinically relevant end point of whether varicocele repair has affected the need for TESE gives this study more weight.
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11
Q
  1. Evidence for role of semen analysis as predictive marker of success of fertility
A
  • Matkov et al., 2001
  • Retrospective study to determine the predictive role of preoperative semen analysis on both seminal improvement and pregnancy rates following varicocelectomy
  • Men with mild to moderate oligoasthenospermia (Total mobile sperm count >5 million) had significantly better seminal improvement following varicocelectomy
  • Varicocelectomy may be the most cost-effective initial intervention
  • Men with a TM < 5 million should be counselled to consider proceeding directly to IVF, particularly if the female partner is more advanced in reproductive age.
  • Even following this, the couple should understand that other options are available and effective such as sperm donation and adoption.
    o Have psychological issue associated with both however
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12
Q
  1. What is Klinefelters syndrome?
    How common?
    Type of infertility?
A
  • Most common genetic cause of nonobstructive azoospermia
  • 3% of all infertile men (Juul, 2003)
  • Chromosomal abnormality XXY
  • NOA caused by progressive GERM cell degeneration however up to 8% of patient have genetically normal sperm in their ejaculate
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13
Q
  1. Evidence for defective sperm in Klinefelters syndrome
A
  • Bergere et al., 2002
  • FISH on tissues obtained from Kleinfelter’s patients showed patches of 46XY spermatogonial stem cells in testes which suggests possibility of normal sperm in testes
  • However, aneuploidy rate was higher in XXY patients than controls. Only done with 4 non-mosaic Kleinfelter’s patients so needs more sample for more power
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14
Q
  1. Diagnosis of Klinefelters
A
  • Often in adulthood in context of infertility – karyotype testing
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15
Q
  1. Treatment of Klinefelters
A
  • As normal sperm may be present – microTESE and ICSI is used to maximise chances of biological paternity
  • Spontaneous pregnancies are very rare
  • MicroTESE – current SSR technique of choice for Klinefelters
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16
Q
  1. What is microTESE and is it successful?
A
  • Opening the testes and microscopically inspect parenchyma to identify most promising areas for sperm extraction
  • Success rate, highly variable
17
Q
  1. Evidence of success rate of microTESE in extracting sperm
A
  • Bernie et al., 2013
  • Average of 52% success rate of sperm extraction in men with non-obstructive azoospermia
  • This is greater than conventional procedures such as fine needle aspiration of the testis, testicular biopsy which are successful in 20-45% of men with NOA
  • The success rate improves in younger patients
  • Counselling and the possibility of freezing sperm to cryopreserve may be an option
18
Q
  1. Evidence for pathophysiology which may beenfit treatment for Klinefelter’s patients
A
  • Wikstrom et al., 2004
  • Non-mosaic 47, XXY boys underwent a single testicular biopsy at every fourth month their puberty
  • Prepubertal and early pubertal boys with KS had diploid germ cells that vanished in early puberty therefore germ cells deplete rapidly
  • Reports contrast to Muller et al. (1995) in which no germ cells were detectable in KS boys beyond the age of 2 yr. Explanation was probably due to cryptorchidism in the boys which is known to decrease germ cell line.
  • Future research is thus required to elucidate the mechanisms activated at puberty that ultimately lead to hypogonadism
19
Q
  1. Evidence for ejaculate ICSI success rate compared with TESE in Klinefelters
    What are the increased risks that need to be counselled for?
A
  • Shows a success rate of around 34%, like that of microTESE and ICSI
  • Negatively correlated to female age however it is recommended over IVF as single sperm chosen – better as more suitable in low sperm count and abnormal morphology
  • Ubaldi, 1999
  • Case control study showed a lower implantation rate in ICSI when sperm is extracted from the testes compared to ejaculation.
  • Staessen et al., 2003
  • 10% higher rate of sex chromosome abnormality in embryos from Klinefelters couples which needs to be counselled to the couples before any ART with numerous potential options available.
20
Q
  1. What is primary ciliary dyskinesia?
    Symptoms?
    Prevalence?
A
  • Primary ciliary dyskinesia (PCD is a rare autosomal recessive disease which affects up to 1 in 10000 births with more prevalence in consanguineous populations (Lucas et al., 2014)
  • It is characterised by chronic upper and lower respiratory tract infections along with infertility due to the immobility of the sperm because of defective sperm-flagella movement
21
Q
  1. Diagnosis of PCD
A
  • Genotyping analysis can be used to detect the chromosomal abnormality
  • The diagnosis for PCD can be obtained from the nasal nitric oxide test (nNO).
22
Q
  1. Evidence for use of nasal nitric oxide in diagnosis of PCD
A
  • Leigh et al., 2013
  • Prospective study, nNO values remain extremely low across all ages, less than 10% of the control group and the disease-specific nNO cutoff value was defined at 77 nl/minute which had a sensitivity and specificity of 99% and 98% respectively.
  • There was low overlap between other respiratory diseases, with only cystic fibrosis falling below the cut off level therefore, CF must be excluded by a quantitative pilocarpine iontophoresis sweat test or CFTR genotype testing
  • One limitation is the inability to standardise the procedure across centre. Nasal condition also affects the results with acute respiratory illness reducing nNO levels, so patients should be symptom free for 2 weeks
  • These results do suggest a non-invasive screening test for PCD
23
Q
  1. Counter-argument for not using nNO in PCD
A
  • Jackson et al., 2016
  • A larger prospective study argued that you should not exclude PCD in low nNO tests and that more specific tests should be performed alongside.
  • The nNO alone was found to miss 10% of cases which supported their idea of using High Speed Video Microscopy (HSVM) and Transmission Electron Microscopy (TEM) to improve accuracy – it is important to note that the cut off value was significantly lower at 30nl/minute and could be a cause to their lower accuracy of nNO.
  • These results promote the thought of combined testing to promote the accuracy of diagnosis however discrepancies in the methods cause be a reason for the different results
24
Q
  1. Treatment of PCD
A
  • Assisted reproductive techniques are (ICSI) and donor sperm injection. ICSI overcomes the factors related to impaired motility and the natural processes for fertilization. ICSI is currently the only treatment option for most PCD/KS patients however evidence behind this remains unclear.
25
Q
  1. Evidence assessing the use of ICSI in PCD infertility
A
  • McLachlan et al., 2012
  • A case report is the extent of research behind ICSI and primary ciliary dyskinesia infertility, showed that immobile sperm can produce a normal live birth using totally immobile sperm which achieved a fertilisation rate of 66%.
  • Rare disease so understudied
  • Further study with a greater number of cases need to be analysed to prove the effectiveness of ICSI but it does show promise in an ART to help primary ciliary dyskinesia
  • To avoid undesirable cycles of treatment with a high possibility of failure or inheritance of genetic diseases, use of a semen donor may be a better option for some patients with severe defects. However, I believe the psychological benefit of conception without a donor is of most value to the couple
26
Q

Papers in Intro

A

WHO 2009
NICE 2013
Centres for disease control and prevention 2009
Greenberg et al., 1978

27
Q

Papers on Varicocele - 4

A

Cortes-Gutierrez et al., 2015
Romeo et al., 2001
Schlegel & Kaufmann, 2004
Matkov et al., 2001

28
Q

Papers on Klinefelters Syndrome 7 -

A 
Juul 2003
Bergere 2002
Wikstrom 2004
Muller 1995
Bernie 2013
Ubaldi 1999
Staessen 2003
29
Q

Papers on PCD 4 -

A

Lucas 2014
Leigh 2013
Jackson 2016
McLachlan 2012

Reproduction and Fertility (6 decks)

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