IVF - babies for those who cannot conceive naturally

Menstrual Cycle

Follicular stage [days 1-13]

• Pituitary gland secretes follicle-stimulating hormone (FSH)
• FSH travels in blood to ovary
• Stimulates development (division) of follicle cells surrounding the oocyte
• Developing follicle cells secrete oestrogen
  • Stimulates proliferation of endometrium and its blood supply
  • Inhibits further secretion of FSH by negative feedback
  • Stimulates pituitary gland to secrete luteinising hormone (LH)
• LH causes ovulation

Ovulation [day 14]

• Mature ovarian follicle bursts and releases a 2° oocyte (NOT an ovum)
  • Happens once a month, menstrual cycle ≈28days
  • Each ovary alternatively releases a 2° oocyte every ≈56days (→56/2)
• LH forms the corpus luteum from ruptured follicle

Luteal phase [days 15-28]

• Corpus luteum secretes progesterone
• Progesterone is responsible for
  • Proliferation of endometrium and its blood supply
  • Development of nutrient fluid glands in uterus lining
  • Inhibition of LSH and LH
• Corpus luteum degenerates (due to inhibition of LH)

Menstruation [days 1-5]

• Also called menses, period, menstrual bleeding
• Sign that not pregnant
• Shedding of the endometrium due to low levels of progesterone and oestrogen
• FSH is not inhibited anymore → cycle starts again

Hormones

Maintaining Pregnancy

• Human Chorionic Gonadotrophin (hCG)
  • Secreted by trophoblast and developing placenta
  • Prevents disintegration of corpus luteum (for 3mo)
  • Thereby, maintains high levels of progesterone
  • Basis for pregnancy test → hCG can be detected in urine
  • Peak in bloodstream after 2mo followed by a slow decline
• Progesterone
  • Secreted by
    • Corpus luteum for the first 3mo
    • Placenta after 3mo (because the corpus luteum degenerates)
  • Prevents menstruation and maintains endometrium
  • Thickens cervical mucus → impermeable to sperm
  • Prepares uterus for implantation

Initiating Labour

• Remember: oestrogen ↑contraction while progesterone ↓contraction of uterus
• During labour, oestrogen:progesterone ratio increases
  • Progesterone falls
  • Oestrogen rises
    • Sensitises the uterus (muscle) to oxytocin
    • Releases relaxin which softens the pelvis
• Pressure of fetus against cervix stimulates stretch receptors by positive feedback
  • Hypothalamus stimulates pituitary gland to secrete oxytocin
  • Oxytocin causes contraction of uterus
  • The higher the pressure, the more oxytocin released, the stronger the contractions

Milk production

• Progesterone inhibits prolactin
• At birth, progesterone levels fall → prolactin levels increase
• Breastfeeding promotes production of milk by positive feedback
  • Nerve impulses travel to hypothalamus
  • Stimulates pituitary gland to secrete oxytocin and prolactin
  • The more milk is removed, the more hormones are secreted
• Oxytocin
  • Stimulates contraction of milk ducts → squeezes milk out
• Prolactin
  • Stimulates milk production
  • Inhibits secretion of FSH and LH → prevents ovulation → less likely to conceive

Contraception

Hormones

• 99% effective (<1:100 women will get pregnant in a year)
• Progestogen-only pill
  • Thickens cervical mucus → reduces sperm motility
  • Inhibits LH production → may prevent ovulation (depends on dose)
• Combined pill (oestrogen + progestogen)
  • Oestrogen inhibits FSH production → prevents follicular development
  • Taken for 21 days - withdrawal bleed for the last 7 days
  • Reduce risk of ovarian and endometrial cancer
  • Higher risk of thrombosis in smokers
• Long-acting progestogen can be given for up to 3mo by injection
• Morning-after pill
  • Contains high doses of progestogen
  • Works for up to 72h after intercourse - works best within 12h

IUD

• 99% effective
• Small plastic and copper device
• Inserted into uterus for up to 10yrs
• Mechanism
  • Stimulates release of prostaglandins by endometrium
  • Copper kills sperm
• Risk of ectopic pregnancy (ovulation not inhibited) and infection
• May cause heavy periods

Barrier

• Condoms
  • Male condom - 98% effective and protect from STDs
  • Female condom - 95% effective and may protect from STDs
• Cap with spermicide
  • 92-6% effective
  • Latex silicon cap is used with spermicide, is put into vagina to cover cervix
  • Must be specifically fitted to make sure it is the right size
  • May protect against some STDs and cancer of the cervix
  • After intercourse, it should be left in place for 6-8h
  • Not used if a woman had toxic shock syndrome (infection due to tampon)

Causes of Infertility

• Low sperm count
  • Varicocele → dilated veins in scrotum
  • Blockage of vasa deferentia
  • Sexually transmitted infections (STDs)
  • Hormone dysfunction
  • Diabetes
• Blocked oviducts
  • STDs

In vitro fertilisation (IVF)

• FSH is injected in woman to stimulate development of several follicles
• Just before ovulation, oocytes are collected from the ovary and matured
• Fertilisation
  • Collected sperm is added to the collected oocyte
  • Nucleus of sperm is micro-injected into the oocyte (intra-cytoplasmic sperm injection)
  • Fertilisation outside the body in a flat glass dish
• Culture to the 8-16 cell stage
• Maximum of three are transferred back into the uterus
• Advantage: possible to screen embryos for genetic defects LINK WITH 3-4-2