Human Bio - Reproduction, Teratogens, reproductive technologies, foetal diagnosis, STIs, foetal development

Teratogen

any factor that can causes physical defects in a developing baby.

Timing of exposure affects the magnitude, there are a greater number of critical developments happening earlier in development. Different systems can be susceptible at different stages

Common teratogens

◦Recreational drugs - alcohol and smoking and others
◦Prescribed drugs - in particular chemo drugs, anti-convulsants and anti-coagulants
◦Environmental exposures - some chemicals and radiation
◦Viruses

Teratogens - Alcohol effects on baby

-Slowed foetal growth
-Low birth weight
-Premature birth
-Miscarriage
-Stillbirth
called foetal alcohol spectrum disorder (FASD)

Birth defects:
Growth deficiency, small head, irregularities of the face such as sunken nasal bridge and narrow eye slits, defects in organs such as heart, arms and legs.
-Physical, mental, behavioural and learning disabilities

Teratogens - Alcohol - likely to be a problem

3 week - 6 week (First trimester) produces most dysmorphia and neurological damage

Mother exposed when they choose to drink

Teratogens - smoking affects on baby

-Abnormal bleeding
-Premature birth
-Miscarriage risk increase
-Reducing oxygen supply and nutrients to baby
-slower growth and development

Smaller weight and size
-increase risk of birth defects such as cleft palate
-impaired development/function of placenta
-sudden infant death syndrome (SIDS)
Growth retardation over long-term.

higher incidence of respiratory problems 1st year.

Teratogens - smoking - likely to be a problem

First - second trimester
Conception - 14 weeks

Exposed when when mother smokes, or exposed to smoke/air pollution

Teratogens - Thalidomide

Chemical,

Thalidomide was first marketed to health professionals as a sedative. However, its use rapidly increased amongst pregnant women due to the drug's ability to alleviate morning sickness.

• How much is a problem:
• A single dose of thalidomid is enough to cause teratogenic effects.

• What are the effects on baby:
• a range of birth defects, most commonly of the developing limbs
• Phocomelia - a congenital deformity whereby the hands and feet are bound to the child's trunk, absent or grossly underdeveloped;
• Disfigurements of the ears, eyes, face, internal organs

Teratogens - Thalidomide - likely to be a problem

Time of exposure determines defect.

It acts between 28th to 42nd day of development (5-7 weeks after the last period). a problem as after 10 days of development the limbs start to appear (as microscopic buds) but become recognisable at around the 42nd day. Arms develop before legs, explaining why Thalidomide affects arms more.

Mother exposed 1960s as a sedative. It was prescribed to people who were pregnant to treat nausea and vomiting in early pregnancy.

Teratogens - Rubella effects on baby

Viral infection, mild flu symptoms in adults and highly infectious.

Congenital Rubella Syndrome (CRS), a condition that develops if the mother is infected with the Rubella virus whilst pregnant, esp in the first three months of pregnancy. As rubella tends to grow in tissues that are just forming.

Affects baby:
Deafness, blindness, heart malformations, brain damage.

Teratogens - Rubella - when is it likely to be a problem

Infection within 10 weeks of pregnancy: 9/10 have birth defects.

Risk of damage decreases as months progress: 4th month -61%
end of pregnancy - 10%

Mother exposed as virus is passed from contact with infected person (sneezes, coughs, direct contact with infected mucus). Vaccines prevent rubella for life.

Foetal development week 4

Size of foetus: 4mm long.

Major developments: Development of muscle segments on either side of tube, to become brain and spinal cord. These blocks of mesodermal tissues increase in number over time.
End of week 4: 30 pairs of mesodermal tissue, as beginning of muscles and vertebrae of spinal column.
Brain is beginning to form
tail evident
heart and liver begin to develop.

Foetal development week 8

Size: 3cm long (top of head to bum), weigh about 1g

Week 5 - arms and leg buds appear. Arm buds more advanced, but both elongate rapidly.
Week 8 end - embryo has a human form and all organs are present (many not functional).
Head = half the size of the embryo
eyes (slits), moved from side of head to forward.
Jaws, nose fully developed. Small earlobes, toes and external sexual organs formed - gender is clear.
General body has developed and basic plan or organs in place - know called foetus

Foetal development week 12

Size: 56 cm, 18g

The internal organs and muscles have grown, and the heartbeat can be picked up on an ultrasound scan. The skeleton is made up from tissue and hardening into bone. Internal sex organs formed.

Foetal development week 16

Size: 18cm, 100g

Posture erect, fingerprints appear and foetus moves, stretching arms and legs. Heart beats at 120-160 bpm, facial expressions occur (though smiling/frowning is random as no muscle control and nervous system not fully developed)
Babies eyes move and skin thickens.

Foetal development week 20

Size: 25 cm, 300g

Foetal movements like kicking, punching and turning can be felt by mother. Sleeping and waking, can be woken by movements from mother. Sucking thumb - sucking reflex being developed.

Foetal development week 24

Size: 27-35cm, 565-680g

Baby responds to light and sound, people can see/feel the baby moving. Layer of fat develops under the skin

Foetal development week 28

Size: 38, 1000g

Moves around vigorously in the uterus. Brain enlarges considerably and surface is furrowed with developed functional areas. males - testes descend into scrotum

Foetal development week 32

Size: 41-45cm, 1800-2200g

Immune system is developing, brain and nervous system fully developed.

Foetal development week 36

Size: 46-48cm, 2700g

Circulatory system is fully developed digestive system needs time to develop

Foetal development week 40

Size: 50cm, 3400g

Diminished foetal activity as it occupies all available space in uterus boys usually 100g heavier than girls. Birth weight can vary considerably (2500-4500g) head is smaller in proportion to the body. Nose is well formed.

Foetal development

Foetus changes position in uterus and lies with head resting inside the curved shape of pelvis. Movements are more restricted than before, growth is slow as placenta begins to fail and become fibrous. Antibodies from mother diffuse across the placenta into baby's blood. Gives baby temporary immunity against diseases the mother is immune to.

Crabs/pubic lice and Scabies

Pthirus pubis and Sarcoptes scabiei - parasite

Treatement: cream

Spread: direct + indirect contact

Symptims: itch

Complications: none

HIV/AIDS

Human immunodeficiency - Virus

Treatment: Anti-retroviral therapy. No cure

Spread: unprotected sex, needle sharing/injuries. body fluid (blood, seminal fluid, vaginal and cervical fluids, breastmilk) from infected person enters bloodstream. Can spread from mother -> child

Symptoms:
- Acute - flu like.
- chronic - asymptomatic. can have ring infections can last 10 years.
- AIDS - weight loss, infections, cancers - virus attacks your immune system.

Complications: Death serious infections increased chances of cancer

HIV stages

Acute - virus rapidly replicates blood numbers are high. immune response overcomes infection and patient recovers.
- chronic - asymptomatic. last 10 years.
- AIDS -Immune system has been damaged to the degree it is no longer able to resist other infections. high viral load and low level of T-lymphocytes.

Trichomonas

Trichomonas Vaginalis - parasite/bacteria

Treatment: antibiotics

Spread: unprotected sex

Symptoms for females: inflammation of the mucus membranes of vagina, discharge, itch
Males: inflammation of urethra - none (commonly), discharge, pain

Complications: premature birth.

Genital warts

Human papilloma virus - virus

Treatment: treating 'lesion' won't get rid of the virus.

Spread: direct contact with infected areas in unprotected sex.

Symptoms: 'rash' - warts and itch

No complications

Syphillis

Treponema pallidum - bacteria

Treatment: antibiotics. Cure possible, surgery required in later stages.

Spread: unprotected sex through break in skin. can spread from mother -> baby thru placenta

Primary - chancre (small sores) = painless, heals in 3-8 weeks.
Secondary - rash (hands + feet for weeks), sore/ulcerated mouth and throat, fever, bone and eye disorders. very contagious, lasts 2 yrs.
Latent - none Tertiary - heart disease, insanity, blindness, physical incapacity, maddness then death.

Gonorrhea

Neisseria Gonorrhoea - bacteria

Treatment: antibiotics

Spread: unprotected sex.
mother -> baby at birth, can infect eyes

Symptoms: Discharge, yellow pus leaking from infected areas pain, and pain during urination (males) as pus blocks urethra.

Complications: pain, infertility of left untreated as it spreads and blocks oviduct or urethra.

Chlamydia

Chlamydia trachomatis - bacteria

Treatment: antibiotics

Spread: Unprotected sex, can spread mother -> baby

Symptoms:
Males: infection of urethra (non-specific urethritis). yellow mucus-like discharge from penis and burning sensation passing urine. Can lead to infection of the epididymus (epididymitis) and infertility

Female: no symptoms. Can develop pelvic inflammatory disease (infection or organs in pelvis region). Can lead to scar tissue due to repeated inflammation, causing blockages and ectopic pregnancy,

Herpes

Herpes Simplex Virus - Virus.
Type 1 - produces cold sores
Type 2 - blisters on genitals

Treatment: Antiviral therapy, medication that reduces pain, saline dressings clean blisters. No cure.

Causes: unprotected sex, mother -> baby. can have life threatning complications.

Symptoms:
painful blisters on genitals, flulike, rashes. Healing occurs (1-2 weeks), virus passes into the nervous system and remains for life. Virus can reinfect at any time.

Infertility

Failure to achieve pregnancy after 12 months of regular, unprotected sexual intercourse.

It is a problem faced by a couple. The causes of infertility are numerous. Approximately 10% of the time, no cause is found. Of the remaining cases, there is a fairly even split - 0ne third are due to problems with the male partner, one third problems with the female partner and one third problems with both.
Infertility affects at least 10% of couples and the number is on the rise.

Consequences of infertility

- not having children
- mental health affects
- breakdown of relationships
- pregnancy is seen as natural that people should achieve. Can lead to feeling inadequate
- pressure from friends and relatives about starting families and peers having effortless success achieving pregnancy

Causes of male infertility

poor sperm production - age previous undescended testicles, hormonal problems, malnutrition, drug use, previous cancer treatment.

Sperm unable to 'exit' - previous vasectomy, significant past infection, tumours or compression of epididymus/vas deferens

Genetic disorders - particularly chromosomal

Erecile dysfunction

Causes of Female infertility

Ovulation problems - age, hormonal disorders (particularly thyroid, PCOS or prolactin producing disorders), malnutrition

Tubal problems - previous PID from STIs, Tubal ligation! Previous surgery for ectopic pregnancy, endometriosis

Uterine problems - congenital abnormalities of uterine shape, fibroids

Cervix- hostile mucous

Genetic abnormalities - particularly chromosomal abnormalities can result in infertility.

Both genders can be affected by immune disorders that cause them to attack their own gametes or those of their partner

Why is infertility on the rise

related to societal function or lifestyle factors.

Generally, people are starting families later - spend longer at school / university, there are expectations of careers for both genders, people know that children are expensive and like to have access to maternity leave and or savings before having children.

age affect fertility in both genders. With female fertility dropping rapidly after 35 (men a bit later)

Malnutrition - both being underweight or overweight affect hormonal function and gamete production. Alcohol and other drugs can also affect fertility

In men, fashion trends and use of laptops (on the lap) affect testicular temperature

Determining methods to treat infertility

If a cause can be identified, and it is amenable to treatment, then that is always a good option.

That may include medical management of hormone disorders, surgery for scarred tubes or removing fibroids, using medication for erectile dysfunction...

In cases where there is no cause found, both partners will be advised to consume a healthy diet, attain a healthy weight, avoid alcohol and other drugs in order to maximise their chances of conceiving naturally

Treating infertility: Inducing ovulation

There are drugs that can be used that will mimic the role of FSH and LH in the development and release of ova.

These are useful on their own when ovulation is the problem, which can result from hormonal disorders.

Predominantly, ovulation induction is used to stimulate the development and release of multiple eggs simultaneously so that they can be 'harvested' surgically and then used in other fertility treatment modalities.

Treating infertility: Artificial insemination (AI)

This involves depositing semen into the female reproductive tract.
There are two options for placement:
◦In the vagina
◦In the uterus (IUI - intra-uterine insemination, Uterine deposition used for hostile mucous)

There are two options for sperm:
◦The male partner
◦A sperm donor

Vaginal deposition is sufficient when there are no concerns about female fertility

The male partner's sperm would be used if it is normal. This could be from donations made and frozen prior cancer treatment, or in event of hostile mucous.
Donor sperm can be used if the male is infertile or if there is no male partner

Treating infertility: Sperm retrieval

In cases of ejaculatory failure or when there are very low numbers of normal sperm being produced, sperm can be surgically extracted from the testis and epididymis.

If normal numbers of sperm are produced and extracted, they can be used for artificial insemination.

In the event of small numbers being retrieved, they are then evaluated and potentially used in other treatment modalities for infertility.

Treating infertility: mixing gametes in the lab advantages

both gametes can be assessed for quality before hand. After mixing, they can be reimplanted into the female at varying stages

- GIFT
- ZIFT
- IVF

Treating infertility: GIFT

Gamete Intra Fallopian transfer:

when the mixture of gametes is inserted directly back into a fallopian tube with fertilisation allowed to happen naturally and uncertainly.

1. hormonal treatment is used to stimulate female to produce more than 1 egg
2. sperm and egg collected and analysed
3. sperm and egg mixed together in a lab
4. sperm and egg injected into fallopian tubes during laparoscopic pregnancy

relies on normal gametes and fallopian tubes

Treating infertility: ZIFT

Zygote Intra Fallopian Transfer

when fertilisation is observed to have occurred in the laboratory and a zygote is inserted back into a fallopian tube before being allowed to travel back towards the uterus for implantation on its own.

Treating infertility: IVF

In vitro fertilisation

- the original 'test tube baby'. Fertilisation occurs in the laboratory and then the zygote is allowed to develop until the early blastocyst stage when it is reinserted into the uterus, ready to implant.
sufficient number and functional sperm are still required to penetrate the zona pellucida to result in fertilisation.

1. hormonal treatment stimulate ovaries so multiple follicles develop
2. control ovulation
3. prepare the uterine lining

ultrasound and blood tests let us know of mature eggs, collected from needle through uterus to ovaries.
eggs and sperm mixed at 37 deg to maximise fertilisation, Fertilisation occurs in the laboratory and then the zygote is allowed to develop until the early blastocyst stage when it is reinserted into the uterus, ready to implant.
sufficient number and functional sperm are still required to penetrate the zona pellucida to result in fertilisation via catheter through uterus

Treating infertility: ICSI

Intra-cytoplasmic sperm injection

If there is significant problems with sperm number + quality and fertilisation is not occurring in the laboratory, a single sperm can be injected directly into an egg.

highly invasive and normal sperm is used. Sperm selection must occur -> incubation occurs until blastocyst development.

The resulting embryo is then reimplanted into the female in the same manner as in IVF.

Treating infertility: surgical sperm retrieval

some men unable to ejaculate, or very low numbers of sperm produced. sperm may be collected through survery to ICSI and IVF. needle collects sperm from epididymis or testis.

Treating infertility: Surrogacy

This is when a woman who is not going to be the mother of the child, is the one who carries the child through embryonic and foetal development.

If a woman has uterine or cervical abnormalities, or general health problems that mean a pregnancy is unlikely to result in a viable offspring, using a surrogate can be the only option if the couple want a child that is biologically theirs.
This is a legal minefield! It is also very expensive!

Concerns of reproductive technologies

◦It's expensive. Who covers the costs? It's not treatment necessary for someone's health, government won't pay, health insurance? Does that mean that only the rich can access it? That's not very equitable!
◦Gametes are often retrieved that are not used, sometimes they have even been fertilised and there are zygotes that are in frozen storage. These are human lives, what do we do with them. the outcomes of embryos have moral considerations.
◦It's 'unnatural'. Was the reason that the couple couldn't get pregnant the result of genetic abnormalities, do the children produced have higher chances of serious illnesses.
◦Some have religious beliefs that object to conception occurring outside of the body or products of conception remaining outside the body!

Foetal disgnosis: normal monitoring

Mothers (and babies) are checked frequently using a variety of methods
Monitoring the mother's weight, blood pressure, urine and abdominal size are all done frequently throughout pregnancy, becoming more frequent as the pregnancy progresses
Mothers will also have their blood group checked, and their blood tested for any abnormal antibodies, as well as making sure they are immune to common viruses and are not infected with STIs

Foetal diagnosis: Imaging of the baby

Babies should not be exposed to x-rays unless absolutely unavoidable (they have a lot of years to go where that radiation exposure could cause problems)
Ultrasound is the mode of choice to look at the baby
The first ultrasound is often around the 8 week mark.
It can be used to check that there is only one baby,
that the heart is beating and
the size of the embryo / foetus is often a more accurate
method of dating the pregnancy than last menstrual periods

Foetal disgnosis: Ultrasounds

Most women will have a scan at ~12 weeks in conjunction with a blood test. This can be used to give information about the chances that the child may have Down Syndrome, Spina bifida or other major abnormality
The 'Anatomy Scan' is usually done at about 20 weeks.
It is a thorough look at the anatomy of the baby now that it is big enough to see things more clearly.
This looks at the baby in a top to toe manner and can report a number of abnormalities

Foetal diagnosis: Maternal genetic testing

Women are offered testing for carrier status for a number of recessive disorders. If the mother is not a carrier, there is no chance that the baby will have the disorder.
If she is found to be a carrier, the father can also be tested before there is a need to test the baby

Foetal diagnosis: Genetic testing babies

If there are any concerns about genetic disorders in the baby, and the family wants to have a definite answer prior to birth (because they may choose to abort the baby), or an early diagnosis will make a difference to the outcome for the baby, there are some options for diagnosis:

◦There are often pieces of foetal DNA present in mum's circulation that can be detected in the laboratory. This is OK if looking for chromosomal abnormalities, but you won't reliable have specific genes available for testing
◦ Invasive options like amniocentesis and Chorionic villus sampling

Foetal disgnosis: Amniocentesis

Invasive genentic testing of a baby
◦Samples the amniotic fluid
◦Obtains fewer foetal cells than CVS so results take longer
◦Can only be done from ~18 weeks once there is sufficient fluid to provide a sample
◦Lower, but still present, risk of miscarriage.
◦The procedure can be done later than that but if abortion is a possible outcome, then it needs to be done before 20 weeks

Foetal disgnosis: Chorionic villus sampling

CVS - invastive genetic testing of a baby

◦Done 11-14 weeks
◦Samples villi from the placenta
◦Risks of bleeding and miscarriage (~2%)
◦Provides a relatively quick answer

Foetal disgnosis: Monitoring in labour

Babies can be monitored through labour, either intermittently or continuously.
Listening to the heart is easily done with an ultrasound probe.
A CTG (Cardiac Tocography) can provide continuous monitoring of the pressure in the uterus and the foetal heart rate. A lot of information about how stressed the baby is can be gleaned from the heart rate

Foetal disgnosis: After birth

Babies are screened with a Guthrie test
This is a heel prick blood test done on ALL babies
It looks for Hypothyroidism, PKU, Galactosaemia, Cystic Fibrosis and a number of other metabolic disorders
These are disorders that are rare, but ones where early diagnosis can make a big difference to outcomes.

How to maintain a healthy pregnancy by changing mum's body to supply the foetus's requirements

In the later weeks where baby needs increased amount of oxygen and nutrients, mother's body adjusts:
- her body functions slow down, allowing nutrients to stay in blood for a longer time, allowing it to more easily diffuse across placenta for foetus's use.

Disadvantages for mother:
- alimentary canal less active and empties out more slowly, constipation is common.
- higher concentration of nutrients in the blood, more are filtered by kidneys and nutrients lost in urine.
- large quantity of blood flows through placenta to supply baby, so increase in blood volume and faster rate of circulation in um's body increases rate heart beats + amount of blood pumped. at the end of pregnancy, increase of 40% of BV

How to maintain a healthy pregnancy by changing diet

Woman needs to increase in energy intake of about 850kJ per day, esp in second half of pregnancy.

Requires protein increase (65g per day). Requirements:
- folic acid (folate) for cell division and making proteins. without it, can have spina bifida (arch of vertabrea doesn't develop) and neural tube defects in babies
- calcium are necessary for normal bone growth, teeth, heart, nerve and muscle development
- fluoride protects from dental problems.
- Vitamin A for cell growth. Demand increases.

Inducing ovulation to treatfertility - medications

Medications such as clomiphene stimulates body to make more FSH
hormone injections of FSH increase the blood levels of the hormone. Human chorionic gonadotropin can be used to trigger ovulation once follicle matured. Females affected by hyperprolactinemia will need to lower prolactin levels so ovulation can occur.

listeriosis

listera infection, mild illness caused by eating food contaminated with the bacterium listeria monocytogenes. Infection in a pregnant woman can be avoided by eating freshly prepared food.

How to maintain a healthy pregnancy despite weight gain

mother gains weight as pregnancy progresses. hormonal changes in pregnancy promote conversion of energy to fat and retention of water in the body. Excessive weight gain is hard to lose after the child is born, esp if mother is not breastfeeding.

how to maintain a healthy pregnancy with exercise

if a pregnant woman is used to exercise, maintaining that is good. if not, then don't randomly start, just walk.

^ exercise is linked with:
- more likely to carry their babies to full term
- better able to maintain stamina during labour
- regain their pre-pregnancy bodies and fitness more quickly.