2015 Group Project 4

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2015 Student Projects 
2015 Projects: Three Person Embryos | Ovarian Hyper-stimulation Syndrome | Polycystic Ovarian Syndrome | Male Infertility | Oncofertility | Preimplantation Genetic Diagnosis | Students
2015 Group Project Topic - Assisted Reproductive Technology
This page is an undergraduate science embryology student and may contain inaccuracies in either description or acknowledgements.

Male Infertility

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse. [1] Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, National Women's Health Policy. [2] Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Background Information

1. <pubmed>24356336</pubmed> This review article introduces the development of male germ cells prenatally and postnatally, as well as the factors which causes the abnormalities and fertility preservation.

2. <pubmed>6793629</pubmed>

Male infertility disorders

Causes of Infertility

Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatazoa to result in pregnancy, or inefficient transport of spermatazoa. The three key parameters for assessing male infertility are spermatazoa count, viability and motility.[3]

Physiology of fertility in Males

Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. [4]

Major Causes of Male Infertility

Varicocele

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. [5] As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatazoa viability, count and motility, are also heavily associated with varicocele. [6] Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. [7] Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatazoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).


Male Reproductive Cancers

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. [8] A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatazoa; one of the key indicators of male infertility. [9].


1. Aydos SE, Karadağ A, Özkan T, Altınok B, Bunsuz M, Heidargholizadeh S, Aydos K, Sunguroğlu A. Association of MDR1 C3435T and C1236T single nucleotide polymorphisms with male factor infertility. PMID 26125837

2. V. A. Giagulli, Carbone, G. De Pergola, E. Guastamacchia, F. Resta, B. Licchelli, C. Sabbà, and V. Triggiani Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility? PMID 24691874

3. Lazaros L, Xita N, Takenaka A, Sofikitis N, Makrydimas G, Stefos T, Kosmas I, Zikopoulos K, Hatzi E, Georgiou I. Semen quality is influenced by androgen receptor and aromatase gene synergism. PMID 23001776

--Z3462124 (talk) 09:53, 27 August 2015 (AEST)

Diagnosis

<pubmed>25038770</pubmed> Different diagnostic techniques to detect male infertility

Treatments

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

Improving Fertility

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available. Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" [10].


Hormones

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both [11]. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation [10].

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol [10]. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite [12]. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone [10]. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.


Antioxidants

Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. However an influx of ROS or deficiency in antioxidants can lead to oxidative stress. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis, ultimately causing decreased sperm viability and motility Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title.


2. <pubmed>26097523</pubmed> The research discussed in this article discusses the advantages of using cerium dioxide nanoparticles (CNPs) to treat male infertility due to its antioxidant effects. The research team experimented on male rats to observe CNP effects on male health and infertility as oxidative stress plays a key role in preventing proper spermatogenesis.


3. <pubmed>PMC4023371</pubmed> Research article also focuses on the effects of oxidative stress on male fertility. It discusses the use of lycopenes as a possible treatment for infertility disorders due to its antioxidant properties, as well as contributing to gap junction communication, modulation of gene expression, regulation of the cell cycle and immunological aspects.


4. <pubmed>15867002</pubmed> Using an antioxidant and vitamins C and E to decrease rates of DNA fragmentation caused by ROS


5. <pubmed>16110353</pubmed> Using Astaxanthin to treat fertility by preventing oxidative damage. Measured its effects by semen analysis, blood serum levels of hormones (LH, FSH and testosterone) = can also use for 'diagnosis'


6. <pubmed>25890347</pubmed> This research focuses on a cause for male infertility - varicocele, an enlargement of the pampiniform venous plexus (varicose vein) within the scrotum, with the influence of ROS can lead to atrophy of the testicle. It has been suggested that protein alteration in the seminal plasma and spermatozoa occur in this condition thus the proteins can act as potential biomarkers to diagnose infertility. If diagnosed, males can undergo surgery to treat this.


7. <pubmed>25885464</pubmed> Discusses the success rate of the microsurgery rat model to treat varicocele that is a causative factor for male infertility. Relates to article number 6


Assisted Reproductive Technologies (ARTs)

References

  1. The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/
  2. The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert
  3. <pubmed>21243017</pubmed>
  4. Stanfield, L. C. Pearson New International Edition Principles of Human Physiology Fifth Edition
  5. Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. Human Reproduction Update, Vol. 7, No. 5 pp. 461-472 retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long
  6. Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. Clinics Vol. 63, No. 6 retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en
  7. Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. Human Reproduction Update, Vol. 7, No. 5 pp. 461-472 retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long
  8. <pubmed>25837470</pubmed>
  9. <pubmed>21044369</pubmed>
  10. 10.0 10.1 10.2 10.3 <pubmed>22958644</pubmed>
  11. <pubmed>26019400</pubmed>
  12. <pubmed>16422830</pubmed>

External Resources