Causes And Risk Factors for Infertility

30 - 40% of all infertility - "male" factor


1. Hormonal problem:
o Quite rare & represent only 1% of all male infertility disorders
o Pituitary tumour & other conditions where the pituitary gland is affected

2. Sperm production problem:
o Sertoli cell-only syndrome
o Maturation arrest à precursor cells are unable to complete their development to sperm in the testis.
o Hypospermatogenesis
o Cryptochisism – Undescended testis
o Genetic causes – Klinefelter’s Syndrome, Down’s Syndrome, etc
o Orchitis – Testes infection, can be viral (Mumps orchitis) or bacterial (epididymo-orchitis)
o Heat:
– Temp: 1-1.5 °c < than body temp (achieved by pampiniform plexus)
– Fever, excessive external heat eg: hot spa, underwear style (tight or loose? Still in reaserch)
o Anti-Sperm antibodies – damaging effect on sperm
o Torsion of testis – blood vessels that supply the testis become twisted
o Varicocele - varicose condition of spermatic cord veins, abnormal valves & dilatation, ¯ sperm count , ‘bag of worms’
o Drugs – anti-cancer drugs, chemicals: pesticides, etc
o Radiation damage – in radiation therapy

3. Sperm blockage:
o Congenital absence of vas deferens – common in Cystic Fibrosis
o Congenital absence of seminal vesicle - ­ acidity of semen
o Infection – eg: gonorrhoea, chlamydia, cause inflammation of reproductive ducts
o Obstruction in region of prostate – infection, ‘cyst’ in prostate gland (congenital)
o Vasectomy

4. Ejaculatory problem:
o Damage to nerve ( pudendal n.) – caused by spinal cord injury, diabetes (neuropathy) & surgery - erectile dysfunction
o Surgery to nerves in pelvis & prostate surgery – may cause damage to sphincter muscle of bladder, lead to retrograde ejaculation
o Timing of intercourse – ref to ovarian & menstrual cycle of female
o Medication – anti hypertensive & anti depression drugs

5. Others:
o Smoking
o Stress
o Excessive alcohol
o Idiopathic – 15%
o 2° causes: Diabetes, obesity, sicke cell disease, chronic renal failure, liver disease, usage of lubricants

· 40 - 50% of infertility - "female" factor

1. Ovulation causes
a. Abnormalities of the thyroid gland
Hypothyroidism leads to increased prolactin release, leading to galactorrhoea. The high prolactin level may prevent normal ovulation, causing decreased fertility, sometimes with irregular or absent menses.
Hyperthyroidism patients have variable menstrual patterns
b. Excessive male hormone (androgens)
Excess androgens in the woman may lead to the formation of male secondary sex characteristics and the suppression of LH and FSH production by the pituitary gland. Elevated levels of androgens may be found in women with polycystic ovaries, or with a tumor in the pituitary gland, adrenal gland, or ovary.
c. Physical stress, psychological stress and extreme lifestyle changes
Stress in women disrupts the hormonal communication between the brain, the pituitary, and the ovary, interfering with both the maturation of an egg and the ovulation process.
d. Poor egg quality
Eggs that become damaged or develop chromosomal abnormalities cannot sustain a pregnancy. This problem is usually age-related -- egg quality declines significantly in the late 30s and early 40s.

2. Cervical causes
This involves inability of the sperm to pass through the mouth of the uterus due to damage of the cervix. Causes include the following:
a. Inadequate or inhospitable cervical mucous
Destroys partner’s sperm
b. Cervical narrowing or "stenosis"
Impedes the passage of semen into the uterus
c. Infections of the cervix
Commonly due to sexually transmitted diseases
d. Immunological infertility
Immune attack of sperm or "sperm allergy" is sometimes diagnosed when the woman's immune system produces "anti-sperm antibodies" that attack her partner's sperm.

3. Pelvic causes
These include any disruption of the normal pelvic anatomy:
a. Scar tissue or "adhesions"
Usually caused by surgery or infection. Pelvic adhesions are actually scar tissue that forms between two or more internal organs. Infertility can occur when the adhesions attach to the ovaries or fallopian tubes.
b. Endometriosis
Endometrial tissue (the uterine lining that sheds with each monthly period) grows outside the uterus
c. Blocked, scarred, or distorted fallopian tubes
Pelvic inflammatory disease (PID) - an infection of the reproductive tract that usually is caused by a sexually transmitted disease but can also stem from a miscarriage, abortion, childbirth or an intrauterine device (IUD).
d. Benign tumors (fibroids) of the uterus
Can interfere with embryo implantation or fetal growth. At least 40 percent of women have these benign uterine tumors, or myomas.
e. Poly cystic ovarian syndrome
Patients whose ovaries contain many small cysts have hormone imbalances and do not ovulate regularly.

4. Uterine causes

a. Thin or abnormal uterine lining
Implantation cannot occur
b. Anatomic problems
Polyps, uterine fibroids, abnormal shape of the uterus, septum or "dividing wall" within the uterus
c. Diethylstilbestrol (DES)
A synthetic oestrogen was given to some women who were at risk for miscarriage during the 1950s and 1960s. Women and men whose mothers took DES while pregnant with them are at high risk for certain reproductive tract cancers and menstrual irregularities. Many DES daughters have an abnormally shaped uterus that can lead to repeated miscarriages. DES sons are prone to cysts in their reproductive tract, undescended testicles and other fertility problems.



· Remaining 10 -30% of infertility - contributing factors from both partners/ or idiopathic

*Estimated that 10 - 20% of couples will be unable to conceive after 1 year of trying to become pregnant.
*Important that pregnancy be attempted for at least 1 year.
- Chance for pregnancy occurring in healthy couples who are both under the age of 30 and having intercourse regularly is only 25 - 30% per month. A woman's peak fertility occurs in her early 20s.
- As a woman ages beyond 35 (and particularly after age 40), the likelihood of getting pregnant drops to less than 10% per month.


Risk factors for infertility:

Multiple sexual partners (increases risk for sexually transmitted diseases)
Sexually transmitted diseases
History of PID (pelvic inflammatory disease)
History of orchitis (Testis infection) or epididymitis in men
Mumps (men)
Varicocele (men)
A past medical history that includes DES exposure (men or women)
Eating disorders (women)
Anovulatory menstrual cycles
Endometriosis
Defects of the uterus (myomas) or cervical obstruction
Long-term (chronic) disease such as diabetes

Source:
Medline - http://www.nlm.nih.gov/medlineplus/ency/article/001191.htm,

advanced infertility institute web site – http://www.fertilitydocs.com/causesof.html

And health A to Z website – http://www.healthatoz.com

Contributed by John Lee

Psychosocial Factors In Infertility

Social factors that play a part in infertility:

1. Current social phenomena: tendency for marriage to occur at a later age, therefore couples trying to start families at later age. Fertility in women decreases with increasing age.
2. Smoking: decreases libido, has been linked to infertility in both males and females, while both cigarettes and marijuana lead to a decrease in sperm density, motility, and morphology
3. Alcohol: interferes with the synthesis of testosterone in males and has an impact on sperm concentration. Alcoholism may delay the sexual response and may be conducive to impotence
4. Stress: Stress hormones have an impact on the hypothalamus gland, which produces reproductive hormones. Severely elevated levels can even shut down menstruation.

One interesting small study reported a significantly higher incidence of pregnancy loss in women who experienced both high stress and prolonged menstrual cycles.

Another reported that women with stressful jobs had shorter periods than women with low-stress jobs.

In males, stress causes a blunted GnRH release, leading to hypogonadism.

Emotions felt by couple because of infertility:
However, while stress does not cause infertility, infertility most definitely causes stress. The stress and deep emotions one feels are the result of infertility, not the cause of it.

1. Loss of the parenthood experience - full adult status, a fulfilling and "usual" life experience, the satisfaction of nurturing a young child all the way up to adulthood, and a sense of living on through them and their children after we die
1. Affects self-esteem, self-image, feelings about femininity or masculinity, and sexual attractiveness
2. Sense of disappointment, and the feeling of emotions and events being out of control
3. Denial, shock and numbness – After trying repeatedly unsuccessfully, feelings of "This can't be happening to us" or "I know next month we will be successful"
4. Anger - usually results from feeling vulnerable or helpless or both.
1. Helpless feelings result from the lack of control that you may feel over your life plan, your body, and your future.
2. A sense of vulnerability evolves from feeling "jinxed," or feeling that life isn't fair. You may feel as if you can no longer count on anything good happening in your life.
5. Shame - associated with faltering self-esteem, and a sense of inadequacy, defectiveness and helplessness.
1. As repeated attempts to get pregnant fail, self-image affected
2. Anguish, self-doubt, and chronic sadness converge as couples come to think of themselves as failing, not only in realizing their own dream to reproduce and nurture, but failing their spouse, parents, and siblings as well.
3. Rejection: In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment.
6. Depression
1. Infertile women report higher levels of stress and anxiety than fertile women, and there is some indication that infertile women are more likely to become depressed.
2. Women trying to conceive often have clinical depression rates similar to women who have heart disease or cancer.
7. Fear and frustration – lack of information about the situation
8. Seeking help – a big decision in itself, requires acknowledgement of a problem, very private issue that you can’t talk to everyone about, pride issues to be contended with
1. Desperation for a child drives the couple to seek help

Individually:
The wife may feel the problem lies with her, feels sorry for the husband (“If he had married someone else, he would have children”), feels inadequate, less of a woman.

The husband may not know how to deal with the problem, middle-class men are most likely to respond by avoiding the issue altogether, lack of communication may make problem worse.

Infertility also affects:
Work – co-workers who keep questioning “Why haven’t you had a child yet?”; feelings of depression (emotional stress) regarding oneself affects work performance

Family – parents who are clamouring for grandchildren, become irritable towards other family members due to emotional stress

Sex – becomes a chore, no longer enjoyable

Emotions felt by couple when undertaking treatment
There are emotional ups and downs relating to medical treatment, the uncertainty about outcomes, and the challenge of having to make important decisions such as when 'enough is enough.'

1. Afraid to proceed with IVF - “playing God?”, “morally right?”
2. Financial issues – treatment plans require a lot of financial planning; “investment”, risky endeavour, how to obtain money (personal sacrifices, loans?)
3. Going through an IVF cycle, getting your hopes up, and then for it to come crashing down again a few weeks later – repeatedly going through this rollercoaster takes a toll (depression)
4. When to stop, or other treatment options – require a lot of soul searching, “Should we adopt?”, feelings similar to above (fear, frustration, disappointment)
   

Sources:
Domar AD, Zuttermeister PC, Friedman R. The psychological impact of infertility: a comparison with patients with other medical conditions. J Psychosom Obstet Gynaecol. 1993;14 Suppl:45-52. PMID 8142988.
Schmidt et al. "The Social Epidemiology of Coping with Infertility." Human Reproduction. 20 (2005): 1044-1052.
http://www.emedicine.com/med/topic1167.htm
http://www.emedicine.com/med/topic3535.htm
http://www.icaa.cc/WCI/articles/000022_3.htm
http://www.fcsupport.org/
http://www.resolve.org/

Investigations for infertility

by Chris

source: http://www.babyworld.co.uk/information/trying/infertilityinvestigations.asp


Hormone tests
The levels of most of the hormones known to play a part in fertility can be checked with a simple blood test. For a woman, this test is usually carried out around Day 21 of the cycle, when the levels of hormones can indicate whether ovulation has occurred and also where any problem might lie. Hormone test levels vary and you need to discuss carefully with your doctor not only what each hormone level means on its own, but also in combination, before moving on.

Sometimes the man is tested too, as hormone problems can affect sperm production.

Semen analysis
For this test, a man will need to deliver a sample of his semen into a sterile container. A ‘good’ test will show that he is producing enough seminal fluid, that there are more than 20 million sperm per ml, that more than 40 per cent of these are moving forward and that at least 70 per cent of them are not abnormally shaped. If the sperm count is poor, another test will probably be carried out since sperm counts can vary.

If the sperm seem to ‘clump together’, further tests may be carried out to check for anti-sperm antibodies. Two additional tests may also be used: the ‘swim-up’ test, which allows the percentage of normal sperm to be established, and microscopic photography, which checks the distance the sperm travel.

Post-coital test
In this test, a couple needs to have intercourse around the time of ovulation, when a woman has ‘fertile’ mucus. A sample of cervical fluid is then obtained from the cervix a few hours later and checked under a microscope to see if motile sperm are present. If a large proportion are moving through, it shows that there is no ‘hostile’ reaction taking place.

However, if sperm aren’t getting through, this test may be followed by the sperm invasion test. A sample of the woman’s fertile cervical mucus is mixed with the man’s semen and examined under a microscope to see how far the sperm penetrate into the mucus.

If they clump together and don’t move forward, or if they die off inside the mucus, this may be because one of the couple is producing antibodies to the sperm. In such cases, a ‘crossover’ test may be done, in which the man’s semen is put on a slide with someone else’s mucus and the mucus is put on a slide with someone else’s semen. This can show where the problem might lie.

Cervical mucus can also be analysed to see if it ‘ferns’ under a microscope. Ferning is a characteristic pattern of fertile mucus and shows whether it is as stretchy as it needs to be to let sperm through.








Physical investigations
Sometimes a woman will know that she has had an infection which may have caused damage to her fallopian tubes, sometimes she won’t. Chlamydia, for example, sometimes produces no discernible symptoms, so the fact that it has damaged the tubes may come as a complete surprise. This is why a check on the state of the fallopian tubes is essential in any investigation of infertility, and there are several ways in which this can be done:


Laparoscopy test
In a laparoscopy, carried out under general anaesthetic, a viewing tube is inserted through a small incision in the woman’s abdomen. The abdomen is inflated with carbon dioxide, which makes it easier for the surgeon to check the uterus, ovaries and fallopian tubes for structural abnormalities, endometriosis and adhesions, as well as possibly repair any problems at the same time. Some surgeons also use a laparoscopy to assess whether the fallopian tubes are open: dye is injected through the cervix and should flow out of the ends of the tubes; if it doesn’t, they are blocked.

A laparoscopy is usually carried out as a day procedure, but it carries the small risks and potential side effects of any operation which requires a general anaesthetic. Some women take several days to recover and can suffer soreness as the carbon dioxide tries to escape again. Despite these drawbacks, the procedure can provide a great deal of useful information, and the tiny scar will fade.

X-ray Test (hysterosalpingography)
Another standard test to assess whether the fallopian tubes are open is hysterosalpingography. Dye is injected through the woman’s cervix into the uterus. This dye shows up on X-rays, so a series of X-rays is taken to check how it is flowing through the fallopian tubes and whether there are any blockages.

Any problems show up immediately, which makes this a useful procedure, but it can cause mild to severe cramps. Another advantage of this test is that you avoid having to have a general anaesthetic and surgery; it is usually done in the hospital’s X-ray department and you can go home soon afterwards, though you may need someone to drive you.

Ultrasound tests (hysterosalpingo-contrast sonography)
A relatively new test for assessing whether the fallopian tubes are open is hysterosalpingo-contrast sonography. A contrast solution is injected through the cervix and ultrasound scanning allows its flow along the tubes to be traced. The procedure takes between 15 and 30 minutes and you can go home straight afterwards. However, it is not suitable for everyone and a laparoscopy may also be recommended for a full assessment of your pelvic cavity.

Ultrasound scanning
Ultrasound scanning is also sometimes used as a diagnostic test. Abdominal ultrasound can give a picture of a woman’s uterus and ovaries and show any fibroids, uterine abnormalities or polycystic ovaries. Ultrasound can also monitor whether eggs are developing and being released from the ovaries. One uncomfortable aspect of abdominal ultrasound is that a full bladder is necessary to allow the ovaries to be seen more clearly. Sometimes transvaginal ultrasound is used and a full bladder is then not needed.

For a man, ultrasound can show whether the sperm are being stored and passed on through the system as they should be.

Endometrial biopsy
If there is doubt whether a woman’s endometrium (lining of the womb) is thickening as it should be in preparation for a developing embryo, an endometrial biopsy can be undertaken. A catheter is inserted through the cervix and a small sample (biopsy) of the uterine lining removed. If the endometrium has not developed as expected for that phase of your cycle, this can indicate a problem with hormone levels. The test can also be used to check for infection and if this is discovered a D&C (dilatation and curettage of the endometrium under general anaesthetic) may be needed.

Surgical exploration of the testes
This is done if no other reason can be found for a man’s infertility. It can check for blockages or infections, and a biopsy may be taken to check whether sperm are being produced and are maturing properly. If the sperm-producing tubules and the sperm in them are normal but a semen analysis shows no sperm, the problem is likely to be a blockage. A vasogram may be performed to pinpoint the blockage: dye is injected and X-rays will outline the ducts and pinpoint any obstructions.

Fertilisation (PowerPoint Version)

Prepared by Ji Keon LOOI

Fertilisation (Word Version)

Fertilisation
Ji Keon LOOI

What needs to happen preceeding fertilisation?
•Da Vinci's Renaissance sketch showed that semen came down from a man's brain through a channel in his spine.

How does your sperm look like?
•The little preformed person in the sperm. An imaginary representation of what a sperm might look like, if able to be seen clearly, drawn by Nicolaus Hartsokeker in Essai de ditropique, 1694.

Fertilisation
•The process of fusion between the male and the female gametes in the ampullary region of the uterine tube

•Spermatozoa must undergo
–Capacitation
–Acromsome reaction
before it is able to fertilise the oocyte

Fertilisation
Phases of fertilisation
•Phase 1
–Penetration of the corona radiata

•Phase 2
–Penetration of the zone pellucida

•Phase 3
–Fusion of the oocyte and sperm cell membranes

Three ways a fertilised oocyte will respond:-
•Cortical and zona reactions
–Release of cortical oocyte granules
–Impenetrable oocyte membrane to other spermatozoa
–Zona pellucida alters its struc and composition to prevent sperm binding and penetration

•Resumption of the second meiotic division
–Second polar body (receives no cytoplasm)
–Definitive oocyte has 22+X chromosome (female pronucleus)

•Metabolic activation of the egg
–Activating factor from spermatozoon
–Early embryogenesis

The main results of fertilisation
•Restoration of the diploid number of chromosomes
–½ from father, ½ from mother
–Diploid zygote

•Determination of the sex
–XX / XY

•Initiation of cleavage
–Forms blastomere à morula à blastocyst


Clinical correlations (to be expanded)
•Contraception techniques
•Infertility
•IVF
•GIFT (Gamete infrafallopian transfer)

Thank you
•Langman’s Medical Embryology 10th Edn

Labelling our posts

To avoid confusion to differentiate between pcl materials from MED2031 and MED2042 since we start with Week 1 again this semester, I would suggest that we label our work according to the title of the week.

I have entered all the pcl titles under this post and they should appear when you type in the first letter into the label slot. Alternatively, click on Show all to display all the pcl title.

Thanks.

Ji Keon