W9 - FERTILITY MANAGEMENT

Question 1

Why is there a need for contraception? What is contraception? Explain the ideal contraceptive

Answer 1

• Due to the rapid rate of population growth and lowered death rates, there is an urgent need to manage our fertility via contraception
• Contraception
  
  • Is the prevention of fertilisation and/or pregnancy
• Ideally it would be
  
  • 100% effective
  • 100% sexually convenient
  • 100% reversible
  • 100% free of dangerous side-effects
  • 100% free of nuisance side-effects
  • 100% maintenance-free
  • Have some positive side-effects
• Unfortunately, the ideal contraceptive does not exist

Question 2

What are the different types of contraceptives? Explain

Answer 2

• Hormonal
  
  • Combined (Oestrogen + progesterone) oral contraceptive (COC) - pill/patch/injection/vaginal ring
  • Progesterone only contraceptive (POC) - pill/injection/implant
  • Post-coital (Progesterone ± oestrogen-based) emergency contraceptives
• Barrier/chemical
  
  • Condom
  • Spermicide
  • Diaphragm
  • Intrauterine device (IUD ± progesterone)
• Surgical
  
  • Tubal ligation
  • Vasectomy
• Natural
  
  • Withdrawal - coitus interruptus
  • Rhythm method
  • Breast feeding - increased prolactin inhibits gonadotropin releasing hormone (GnRH) release from the hypothalamus and thus release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary

Question 3

What are the different types of hormonal contraceptives? Explain

Answer 3

• Combined oral contraceptive (COC)
  
  • Supressed follicle stimulation, ovulation and corpus luteum formation (E2)
  • Thickens cervical mucus (P4)
  • Disrupts oviductal transport and create hostile endometrium (P4)
• Progesterone only contraceptives (POC)
  
  • Thickens cervical mucus (P4)
  • Disrupts oviductal transport and create hostile endometrium (P4)

Question 4

What are the risks associated with oestrogen exposure in susceptible individuals?

Answer 4

• Risks
  
  • Increased risk of endometrial cancer - may overstimulate cell proliferation
  • Increased risk of cardiovascular complications - heart attack, stroke and blood clots

Question 5

Define failure rate. What form of contraceptive offers the lowest failure rate?

Answer 5

• Failure rate
  
  • How often method fails if used exactly as directed
• 1% failure
  
  • 1 woman would fall pregnant if 100 women used the method for 1 year
• Typical failure rate much higher than perfect use
• Surgical sterility offers lowest overall failure rates
• Hormonal methods are relatively effective (If used carefully)
• Barrier/chemical methods high typical failure (User error)
• Natural methods are the least reliable
• Method
  
  • Surgical - ideal failure rate (0.1-0.2); typical failure rate (0.15-0.40)
  • Hormonal - ideal failure rate (0.1-1.0); typical failure rate (0.3-10)
  • Barrier/chemical - ideal failure rate (0.8-9.0); typical failure rate (4-28)
  • Natural - ideal failure rate (1.9-15); typical failure rate (18-50)

Question 6

What are some important consideration when selecting the correct contraceptive?

Answer 6

• Important considerations
  
  • Effectiveness (Failure rate)
  • Ease of use
  • Side effects (Patient profile)
  • Cost
  • Availability and acceptability

Question 7

What does the combination pill contain? What are its actions and failure rate? List some advantages, disadvantages and contraindications of the combination pill

Answer 7

• Contains synthetic oestrogen and progesterone
• Actions
  
  • Inhibits ovulation - inhibits tertiary ovarian follicle growth and prevents surge of FSH and LH from anterior pituitary that normally causes ovulation
    
    • Mimics negative feedback effect of oestrogen and progesterone in the luteal phase
    • Does not prevent follicle development but blocks LH surge and FSH-dependent growth to ovulatory stage
  • Thickens cervical mucus (sperm cannot pass this barrier)
  • Endometrium is unreceptive to the embryo due to incorrect oestrogen:progesterone ratio
    
    • No oestrogen stimulated endometrial adhesion molecules and endometrium has altered growth and function
• Very effective - 1% failure rate
• Advantages
  
  • Works on 3 levels (ovulation, sperm movement, endometrial disruption) - lowers failure rate
  • Regular and light menses
  • Decreased uterine cramping
  • No interruption of sex
  • Protects against ovarian and endometrial cancer (less ovary stimulation)
• Disadvantages
  
  • Require prescription, fertility does not return for several months, cannot be taken when nursing
  • Risk of sexually transmitted infections is not prevented
  • Needs to be taken every day - not convenient
  • Side effects - nausea, breast tenderness, headaches (10-15%)
  • Several contraindications
    
    • Migraine with aura
    • Blood clotting risk
    • Less than 21 days after delivery
    • Recent breastfeeding
    • Smokers over 35
    • Obesity over 35
    • Hypertension
    • Diabetes

Question 8

What does the minipill contain? List some advantages, disadvantages and contraindications of the minipill

Answer 8

• Small amount of progesterone
• Take daily even during menstruation
• Contraception may take a while to be protective
• Blocks ovulation, thickens cervical mucus, disrupt transportation and implantation of the early embryo
• Fewer side effects, higher failure rate
• No contraindications of progesterone only contraceptive
• Can be used for those contraindicated for combined oral contraceptive

Question 9

What does the intradermal progesterone implant contain? List some advantages, disadvantages and contraindications of the intradermal progesterone implant

Answer 9

• Similar to minipill actions
• Visible under the skin
• Convenient, does not interfere with lactation
• Low failure rate
• Removal can result in scarring, muscle and nerve damage
• Side effects
  
  • Dizziness, depression, fuzzy thinking, moodiness, numbness in arms and legs, weight gain, month-long menstruation, increased brain fluid pressure
• New ones dissolve - last 3 years
  
  • Lower level of progesterone could mean fewer side effects compared to the old one
• Fertile 3 months after removal

Question 10

What do injectable hormones contain? List some advantages, disadvantages and contraindications of injectable hormones

Answer 10

• Progesterone is injected every 90 days
• Blocks LH surge and hence ovulation
• Combination is also available
• Low failure rate, do not need to remember about the daily pill
• Fertile 3-18 months after last injection

Question 11

What does transdermal hormone delivery contain? List some advantages, disadvantages and contraindications of transdermal hormone delivery

Answer 11

• Contraceptive patch
• Constant flow of hormones through skin
• Applied once a week for 3 weeks (on same day of each week), 4^th patch is hormone free, causing menstruation
• As effective as combination pill
• Ovulation prevented, cervical thickening
• Includes transvaginal rings, releasing hormone across the vaginal epithelium and enters the bloodstream

Question 12

What does emergency contraception contain? List some advantages, disadvantages and contraindications of the emergency contraception

Answer 12

• Oestrogens and/or progesterone after unprotected sex
• “Plan B” - progesterone only - two pills
• Inhibits ovulation, interferes with the transport of the pre-embryo down the oviduct, alters the endometrium so that implantation does not occur
• Not effective if implantation has already occurred
• Side effects
  
  • Nausea and vomiting
• Failure rates are fairly high

Question 13

What do intrauterine devices contain? List some advantages, disadvantages and contraindications of intrauterine devices

Answer 13

• T-shaped piece of flexible plastic placed through the cervical canal into the uterine cavity
• Wrapping of copper wire around the plastic or contain progesterone
• Reduces sperm count in uterus and cervix - affects development and maturation of the ovum
  
  • Foreign body - causes inflammation and white blood cells in uterus - block implantation
• Copper is more effective than plastic
• Copper can be left in for 10 years - may have a toxic effect on sperm and/or interfere with capacity to fertilise an egg or interfere with the role of zinc in implantation
• Employed post-coitally to block implantation - highly effective

Question 14

What are spermicides?

Answer 14

• Mechanical barrier to sperm transport and adverse effects on sperm
• Inert base accompanied by an active ingredient

Question 15

What is a diaphragm?

Answer 15

• Shallow cup of thin rubber stretched over a flexible wire ring
• Placed inside the vagina so that it covers the external cervical os
• Prevents sperm from entering the cervical canal

Question 16

Define fertility, infertility, clinical infertility, fecundability and fecundity in relation to infertility and assisted reproductive technologies

Answer 16

• Fertility
  
  • Capacity to conceive and produce offspring
• Infertility
  
  • Diminished capacity to conceive and bear offspring (not irreversible in contrast to sterility)
• Clinical infertility
  
  • Inability to conceive after 12 months of frequent unprotected intercourse
• Fecundability
  
  • Probability of achieving a pregnancy in 1 menstrual cycle (0.25 in healthy young couples)
• Fecundity
  
  • Ability to achieve a pregnancy resulting in live birth in 1 menstrual cycle
• According to statistical models 98% of couples should conceive within 1 calendar year

Question 17

What are the causes of infertility in males and females?

Answer 17

• 35% female, 35% male, 20% both and 10% unknown
• Female factors
  
  • Ovulation and ovarian failure (hormone imbalance, polycystic ovarian syndrome, hypoplasia)
  • Blockage of oviducts
  • Implantation failure (abnormal endometrium, fibroids/polyps, hormone imbalance)
  • Failed sperm transport (vaginal acid, abnormal cervical shape or mucus)
  • Anti-sperm antibodies
  • Miscarriage (aged/abnormal oocytes = poor quality)
• Male factors
  
  • Poor sperm number/motility/morphology (hormone imbalance, hypogonadism)
  • Testes and accessory gland dysfunction (cryptorchidism, varicocele, drugs/toxins)
  • Blocked ejaculatory ducts
  • Ejaculation disorders (retrograde, neurological)
  • Anti-sperm antibodies

Question 18

Explain the problems with meiotic arrest in aged oocytes

Answer 18

• Prolonged arrest in prophase 1 can last up to 50 years
• Cohesive proteins (cohesins) that keep sister chromatids together weaken with age causing
  
  • Incorrect microtubule - centromere attachment
  • Chromosome segregation errors (non-disjunction) predominantly during metaphase 1
• Increase in aneuploidy (e.g. trisomy 21) with increasing maternal age

Question 19

Explain how down syndrome increases with maternal age. How common is this disorder and how much higher is the risk of having a child with trisomy 21 in 45 year-olds in comparison to 20-24 year-olds?

Answer 19

• Down syndrome (trisomy 21) is the most common chromosomal aneuploidy (1 in 1,000 births)
• Chance of child with trisomy 21 increases with mother’s age
  
  • 44x higher risk in 45 year-olds than 20-24 year-olds (1 in 32 vs. 1 in 1,411 births)
• Chromosome segregation errors (non-disjunction) increases in aged oocytes

Question 20

What are some methods of primary and secondary laboratory analysis to indentify the causes of infertility?

Answer 20

• Primary laboratory analysis
  
  • Hormone assays (detect cycling and ovulation, or spermatogenesis)
  • Ultrasound (presence of follicles or cysts, endometrial thickness)
  • Test tubal patency (radio-opaque dye)
  • Semen analysis
  • Blood tests (anti-sperm antibodies)
• Secondary analysis
  
  • Laparoscopy/endoscopy (uterine/oviduct blockage)
  • Endometrial biopsy
  • Testicular biopsy

Question 21

What are the ranges for determining sub-fertility in sperm?

Answer 21

• Primary laboratory analysis
  
  • Semen analysis of number, volume, motility, morphology, DNA damage
• World health organisation 2010 semen lower reference limits (normozoospermia)
  
  • Volume - greater than 1.5mL (1.4-7.6mL)
  • pH - greater or equal to 7.2
  • Sperm count - greater than 15 million/mL (concentration); greater than 37 million (total)
  • Morphology - greater than 4% normal
  • Motility - greater than 32% (progressive); 40% (total)
  • Viability - greater than 58% live
• Sub-fertile sperm
  
  • Oligozoospermia - less than 15 million/mL
  • Azoospermia - no sperm
  • Aspermia - no ejaculate

Question 22

What are some assisted reproductive technologies (ART) available today?

Answer 22

• Infertility treatments that involve manipulation of oocytes, sperm or embryos in vitro
  
  • Artificial insemination (AI)
  • In vitro fertilization (IVF)
  • Intracytoplasmic sperm injection (ICSI)
  • Gamete intrafallopian transfer (GIFT)
  • Zygote intrafallopian transfer (ZIFT)
  • Cryopreservation of sperm, oocytes or embryos

Question 23

What is artificial insemination? Explain its process and reason

Answer 23

• Definition
  
  • Introduction of spermatozoa into the female reproductive tract by means other than sexual intercourse (I.e. Artificially)
• Process
  
  • Most motile/functional sperm isolated by percoll gradient
  • Intrauterine insemination (IUAI) by catheter
  • Synchronized with natural or induced (FSH and LH) ovulation
• Reason
  
  • Problem with sperm

Question 24

What is in vitro fertilisation? Explain its process and reason

Answer 24

• Conventional in vitro fertilization (IVF)
  
  • Oocyte retrieved from ovary
  • Sperm artificially capacitated
  • Natural penetration, fusion/fertilization in vitro
  • Embryo cultured in vitro then blastocyst transferred to uterus for natural implantation
  • Reason - poor motility or sperm numbers, or tubal blockage
• Intracytoplasmic sperm injection (ICSI)
  
  • Similar to IVF except
  • Fertilization incompetent sperm “hand-picked”
  • Directly injected into oocyte (natural fertilization bypassed)
  • Injected oocyte chemically “activated” to develop
  • Reason - often immotile or fertilisation incompetent sperm

Question 25

What is in zygote intrafallopian transfer? Explain its process and reason

Answer 25

• Zygote intrafallopian transfer (ZIFT)
  
  • Like IVF except newly fertilised zygote transferred back to oviduct
  • Tubal blockage and/or very poor sperm motility or numbers (less common)

Question 26

What is in gamete intrafallopian transfer? Explain its process and reason

Answer 26

• Gamete intrafallopian transfer (GIFT)
  
  • Oocyte transferred to oviduct by bypassing the blockage followed by intrauterine artificial insemination (IUAI)
  • Reason - tubal blockage

Question 27

Explain the rational for different assisted reproductive technologies in males and females

Answer 27

• Male infertility factors
  
  • In order of decreasing sperm quality
    
    • AI
      
      • Sub-optimal motility or numbers
    • IVF
      
      • Very poor motility or numbers
    • ICSI
      
      • Often immotile or fertilisation incompetent
• Female fertility factors
  
  • In order of different stages of embryo development
    
    • GIFT
      
      • Tubal blockage
    • ZIFT
      
      • Tubal blockage and/or very poor sperm motility or numbers (less common)
    • IVF
      
      • Tubal blockage and/or very poor sperm motility or numbers