12 - FERTILITY TREATMENTS: INFERTILITY AND ASSISTED REPRODUCTION Flashcards

1
Q

What is Reproductive Health?

A

• Reproductive health is defined by 3 measures:

  1. control
  2. success
  3. safety
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2
Q

Control

A

natural, pharmaceutical, surgical and barrier methods

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3
Q

Success

A

Potential and Outcome affected by age, general health and previous
pregnancies, social factors, inequalities

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4
Q

Safety

A

sex and birth are dangerous things: sexually transmitted disease,
infection, problems with delivery and pregnancy, miscarriage.
But risks can be controlled and minimised with good healthcare and education

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5
Q

What is Birth Control?

A
  • Increased reproductive choice links to improvements in ecology, economics, equality and social change.
  • Unregulated fertility is a significant contributor to infertility.
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6
Q

INFERTILITY

A
  • Couple is defined as infertile following 12 months of trying to conceive (sex every 2-3 d) (NHS)
  • treatment after 2 years, may be sooner if secondary infertility , with age as a possible factor
  • Multifactorial: male, female, combination, unexplained
  • Affects 88 million couples, 186 million individuals (WHO)
  • Male infertility only recognised in the latter half of the C20
  • 50-70% asymptomatic
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7
Q

What are the underlying causes of infertility in males and females?

A
  • Incompatibility i.e. uterine pH.
  • Antibodies to sperm (♀ or ♂).
  • Medications.
  • Knowledge and opportunity.
  • Genetics: embryonic lethality.
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8
Q

What are the underlying causes of infertility in males?

A
  • Sperm quality.
  • Absence or blockage of ducts.
  • Lack of gonadal tissue (Testes).
  • Illness or Sexually Transmitted Diseases i.e. chlamydia.
  • Sperm destruction.
  • No sperm produced.
  • Lack of ejaculation.
  • Low testosterone
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9
Q

What are the underlying causes of infertility in females?

A
  • Age (of oocyte).
  • Problems with oocyte maturation and/or ovulation (oocyte or hormonal); common cause of fertility problems is polycystic ovary syndrome (PCOS).
  • Lack of gonadal tissue (Ovaries).
  • Lack of uterus or differences in uterine anatomy.
  • Stage of uterine development (hormonal).
  • Blockage of uterine tubes.
  • Stress-physical and mental.
  • Uterine scarring.
  • Endometriosis and Pelvic Inflammatory Disease (PID).
  • Cervical mucus.
  • BMI.
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10
Q

SECONDARY INFERTILITY

A

Majority of people experiencing infertility have already had a
child: 1.9% females 20-44 experience primary infertility
versus 10.5% for secondary*

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11
Q

FERTILITY TREATMENT

REQUIREMENTS

A

• Donation/extraction of sperm
• Donation/extraction of oocytes
- Synchronisation of cycles
- Surrogate parent (where there are problems with uterus or giving birth)

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12
Q

FERTILITY TREATMENT CONSIDERATIONS

A

• Screening for infectious disease: sexually transmitted diseases, HIV, blood-borne viruses, hepatitis B and C, human T cell lymphotropic viruses (known to cause a type of cancer).
• Family history of Disease/genetic testing
- Pregnancy
- Hyperstimulation of ovaries

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13
Q

What is artificial insemination (AI or IUI)?

A
  • Devised in 1790s by Dr John Hunter.
  • Woman is inseminated with epididymal sperm.
  • Treats idiopathic infertility, paraplegia, obstructed vas deferens, long separation or illness, same sex couples or single women and post-mortem.
  • 15-30% success in cycles: dependent on sperm quality (morphology, motility, direction, speed).
  • Cheaper than IVF, fewer procedures.
  • Sperm improved with use of ‘swim-up’ technique: selecting for healthy sperm (swimming the right way etc).
  • Sperm reaching the top layer are aspirated and washed for use.
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14
Q

What is intrauterine insemination (IUI)?

A
• Sperm placed high in the uterus, Bypasses 'hostile' mucous.
• Overall, 60-70% success over 6 cycles.
• Success per cycle was:
1) 15.8% for women under 35
2) 11.0% for women aged 35-39
3) 4.7% for women aged 40-42
4) 1.2% for women aged 43-44
5) 0% for women over 44
• Success depends on sperm count, quality. 
• Frozen sperm has no effect.
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15
Q

What is the history of infertility treatments?

A
  • In Vitro Fertilisation was first used in the 1970s.
  • Louise Joy Brown, conceived by IVF in Oldham General Hospital.
  • Technology had been in development for 20 years+ Steptoe and Edwards.
  • Sperm and eggs removed and fertilisation occurs outwith the body.
  • Healthy embryo is implanted in the uterus.
  • Offered to those who have not conceived after IUI.
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16
Q

IVF ELIGIBILITY

A
  • 2 years of unsuccessful attempts to conceive
  • Females must be <43
  • had 12 unsuccessful rounds of IUI
  • Where genetic testing is required
  • Blocked uterine tubes
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17
Q

How are eggs retrieved, stored or donated for IVF?

A

• Hormonal treatment is given to suppress the natural (endogenous) cycle:
1) Gn RH agonists inhibit pituitary function.
2) GnRH antagonists inhibit LH/FSH release.
• Exogenous hormones stimulate/control ovulation:
1) Growth of oocytes occurs by Follicle Stimulating Hormone for 10-12 days or clomiphene citrate (not good with PCOS).
2) Maturation of oocytes occurs by artificial LH surge through human Chorionic Gonadotrophin (hCG).
3) Monitoring of oocytes is done by ultrasound and harvesting of oocytes (aspiration) completed transvaginally.
4) Hormones are given to prepare uterus (Progesterone) by injection or vaginally; pestrogen can also be given.
5) Aspiration from the ovary is followed by incubation with sperm for 12-16 hours
6) Evidence of a polar body is indicative of a healthy zygote; this can be collected for preimplantation genetic testing.
7) Viable zygotes cultured for several days (up to 6d), until a healthy blastocyst forms; there is transfer to uterus by a catheter; transplantation number is limited by the UK HEFA

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18
Q

Aspiration

A

involves assessment of the eggs via ultrasound then aspiration of the oocyte from the ovary;
this usually involves inflation of the abdomen to allow for manipulation and can be uncomfortable
the egg is incubated with sperm to allow fertilisation to occur
this is identified by evidence of pronuclei and polar body formation
testing is done on the polar body to prevent destruction of the zygote.

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19
Q

How is the quality of eggs determined?

A
  • Good egg: Large egg with a polar body.
  • Day one: Fertilised egg with 2 pronuclei.
  • Day two: 4 cells.
  • Day three: 6-8 cells.
  • Day five: Blastocyst has a hollow ball of cells with good trophoblast and Inner Cell Mass (ICM); Removal of trophoblast for PGT.
  • Day six: Blastocyst ‘hatches’
  • Implant day 5-5.5.
20
Q

TRANSGENDER IVF

A
  • Options vary depending on medical transitioning ie may need to freeze eggs or sperm before surgery
  • Transwomen may need clomiphene citrate or hCG injections to stimulate sperm production. Long-term hormone treatment may adversely affect sperm production
  • Transmen need to come off testosterone (3-6 months withdrawal) as it is damaging to the development of the fetus. Some transmen will start to cycle, some will need hormonal treatment for egg retrieval and to get IVF and implantation into someone’s uterus (surrogacy).
  • effect of removal of testosterone will have an effect on mood, mental health and body shape that people find upsetting
21
Q

PROBLEMS WITH IVF

A
  1. Emotional
  2. Expensive
  3. Uncomfortable and invasive
  4. Superovulation can lead to multiple pregnancies without contraception
  5. Multiple birth (>1 blastocyst transplanted)
  6. Ectopic Pregnancy
22
Q

Ovarian Hyperstimulation Syndrome (OHSS)

A
  1. Increased permeability of capillaries
  2. Oedema: tissue and pulmonary
  3. Renal failure
  4. 8% mild
  5. < 1% severe
23
Q

How is sperm quality determined?

A
  • Successful IUI and IVF relies on good quality sperm, eggs and fertilised eggs (blastocysts).
  • Only about 100 sperm from ejaculate make it to the isthmus.
24
Q

Why might there be no semen in ejaculate?

A
  • Vasectomy.
  • STD such as chlamydia.
  • Chemotherapy treatment.
  • Unable to ejaculate.
  • Antibodies to sperm.
25
Q

Sperm retrieval

A
  • Sperm retrieval is required; Surgical sperm extraction or aspiration.
  • Involves aspirating semen from the testicle or epididymis.
  • Sometimes a section of tubule is removed from several sites and sperm removed under the microscope.
26
Q

Types of surgical sperm extraction?

A

PESA, MESA, TESA, TESE, micro-TESE

27
Q

PESA

A

Sperm aspirated from the epidydymis

28
Q

MESA

A

Collection of sperm with use of a microscope directly from epidydymal tubule.

29
Q

TESA

A

Sperm aspirated from testes directly through the scrotum (Non-obstructive).

30
Q

TESE

A

Biopsy of testes, removal of sperm from biopsy (Non-obstructive)

31
Q

micro-TESE

A

Biopsy of testes, removal of sperm from biopsy, but use of a microscope to identify areas more likely to contain mature sperm (enlarged).

32
Q

IVF MODIFICATIONS: ICSI

A

Intracytoplasmic Sperm Injection (ICSI)
When sperm quality is low:
• Poor motility
• Low number
• Abnormal morphology (see previous slide)
• Frozen rather than fresh sperm used
• Sperm injected straight into harvested egg
• All other parts of IVF are as normal, although the oocyte may be harvested before maturation, and matured in the lab to reduce female treatments (In vitro Maturation; IVM)

33
Q

IVF MODIFICATIONS: FET

A

Frozen Embryo Transfer (FET):
• May be used if there are problems with implantation. Gives time for body to recover
• If Preimplantation Genetic Testing is being carried out on Trophectoderm cells
• If a number of high quality embryos were collected but further full treatment is not an option
• For future years to increase family
• May have increased success rate, decrease premature birth and maternal bleeding (Bhattacharya 2012, 2016)

34
Q

HOW DO ANTIBODIES TO SPERM ARISE? - male

A

• Vasectomy
• Damage to the spermblood barrier
• Dysfunction of Sertoli cells (SB barrier)
Consequences: infertility
1. destruction of sperm
2. clumping of sperm; disrupting travel to oocyte

35
Q

HOW DO ANTIBODIES TO SPERM ARISE? - female

A

• Damage to mucosal membranes
• Exposure to sperm in the digestive tract
• Infection
Consequences: infertility
1. destruction of sperm
2. clumping of sperm; disrupting travel to oocyte

36
Q

What are the 3 ways to deal with a low sperm count?

A

Concentration by centrifugation, wash to remove dead sperm and WBC or intrauterine insemination

37
Q

What is the criteria for normal male seminal fluid?

A

Over 2ml volume, over 20 million sperm per ml, ha,f move forward within an hour, 30% move with normal morphology, 75% alive, less than 1 million WBC per ml.

38
Q

What is GIFT?

A

gamete intrafallopian transfer

Oocytes from stimulated ovaries are mixed with sperm and inserted into the oviduct.

39
Q

What is ZIFT?

A

zygote intrafallopian transfer

Oocytes from stimulated ovaries are mixed with sperm and fertilise them before being put into the oviduct.

40
Q

What is azoospermia?

A

absence of sperm in ejaculate
Solved by artificial insemination from anonymous donor. Being froze decrease viability by 30%.
Could have sperm in the epididymis or seminiferous tubules.

41
Q

What is PGD?

A

preimplantation genetic diagnosis

Check of blastocyst, incubated for 5 days and trophectoderm cells are removed.

42
Q

What is PGD?

A

preimplantation genetic diagnosis

Check of blastocyst, incubated for 5 days and trophectoderm cells are removed.

43
Q

What is oocyte donation?

A

Involves the deliberate use of oocytes provided by the donor for invitro fertilization
Donors may be either unknown or known
Usually young women who are paid to donate
Recipients: women w/ diminished ovarian reserve, advanced maternal age, used to avoid transmitting a genetic illness
Hard to freeze due to 130 mm diameter

44
Q

How can you control ovulation?

A

Artificial Lh and Fsh surge and endogenous cycle inhibited

45
Q

What are the super-ovulation risks?

A

Multiple pregnancies, hyper stimulation hormone, renal failure, monitored by ultrasound.

46
Q

What are anti sperm antibodies?

A

Clump sperm together so the zone pellucida binding is inhibited. Then phagocytosis.

47
Q

What is male ASAS?

A

Sertoli cells being sealed off causing immunosuppressive mechanisms. Sperm autoantibodies may arise and bind to sperm in the vans deferens.