Causes of infertility

• Infertility


  Couple is defined as infertile following 12 months of trying to conceive (sex every 2-3 d) (NHS)
• Eligibility for infertility treatment

  Eligible for treatment after 2 years, may be sooner if secondary infertility , with age as a possible factor
• Infertility is multifactorial: male, female, combination, unexplained
• Infertility affects 88 million couples, 186 million individuals (WHO)
• Male infertility only recognised in the latter half of the C20
• 50-70% of infertility cases are asymptomatic
• Infertility causes problems for both parties: emotional, medical interventions (burden on female), guilt etc.
• Causes of infertility

  • Sperm quality
  • Age (of oocyte)
  • Incompatibility (uterine pH)
  • Absence or blockage of ducts
  • Problems with oocyte maturation and/or ovulation
  • Antibodies to sperm
  • Lack of gonadal tissue (Testes/Ovaries)
  • Medications
  • Illness or Sexually Transmitted Diseases
  • Lack of uterus or differences in uterine anatomy
  • Sperm destruction
  • Stage of uterine development (hormonal) ie mismatch of ovarian and uterine cycles
  • Genetics: embryonic lethality
  • No sperm produced
  • Blockage of uterine tubes
  • Lack of ejaculation
  • Stress- physical and mental
  • Low testosterone
  • Uterine scarring
  • Endometriosis and Pelvic Inflammatory Disease (PID)
  • Cervical mucus/environment
  • Medications
  • BMI
• Infertility rates are not the same worldwide, with higher rates in tropical Africa due to factors like infection, damage, and insufficient recovery
• Secondary infertility


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


  • Physical: Age, underlying health conditions, medications, weight gain, scarring from previous pregnancies, fibroids, damage from infections
  • Psychosocial: Attitudes from community less supportive, pressure on parents as see it as a "bigger" failure
• Requirements for fertility treatments

  • Donation/extraction of sperm
  • Donation/extraction of oocytes
  • Synchronisation of cycles
  • Surrogate parent (where there are problems with uterus or giving birth)
  • Screening for infectious disease: sexually transmitted diseases, HIV, blood-borne viruses, hepatitis B and C, human T cell lymphotropic viruses
  • Family history of Disease/genetic testing
  • Pregnancy
  • Hyperstimulation of ovaries
• Fertility treatment requirements in the UK are regulated and licensed by the Human Fertility and Embryology Authority (HFEA) and the Human Fertility and Embryology Act 1990
• Artificial insemination (AI or IUI)


  Inseminated with epididymal sperm, treats idiopathic infertility, paraplegia, obstructed vas deferens, long separation or illness, same sex couples or single women and post-mortem
• Success rates of IUI

  • 15-30% success in cycles: dependent on sperm quality (morphology, motility, direction, speed)
  • Cheaper than IVF, fewer procedures
• Intrauterine insemination (IUI)


  Sperm placed high in the uterus, bypasses "hostile" mucous, overall 60-70% success over 6 cycles
• Success rates of IUI depend on sperm count, quality, and age of the woman, with lower success rates for older women
• In Vitro Fertilisation (IVF)


  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
• In Vitro Fertilisation developed

  1970s
• Louise Joy Brown


  First baby conceived by IVF in Oldham General Hospital
• Robert G. Edwards


  Awarded the Nobel Prize in Physiology or Medicine 2010 for the development of in vitro fertilization
• IVF Eligibility (for NHS)

  • 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
• Success rates of IVF decrease with maternal age, with under 35s having a 40.6% success rate over 3 cycles compared to under 1% for 45+
• Retrieving Eggs for donation, storing or IVF

  1. Hormonal treatment to suppress natural (endogenous) cycle

  2. Exogenous hormones to stimulate/control ovulation and maturation of oocytes

  3. Monitoring of oocytes by ultrasound and harvesting of oocytes (aspiration) completed transvaginally

  4. Hormones given to prepare uterus (Progesterone) by injection or vaginally, Oestrogen can also be given
• In Vitro Fertilisation

  1. Aspiration from the ovary is followed by incubation with sperm for 12-16 hours

  2. Evidence of a polar body is indicative of a healthy zygote, this can be collected for preimplantation genetic testing

  3. Viable zygotes cultured for several days (up to 6d), until a healthy blastocyst forms

  4. Transfer to uterus by catheter, transplantation number is limited by the UK HEFA
• Implantation of the fertilised egg occurs on day 5-5.5, with the ICM and trophoblast needing to have a reasonable number of well-connected cells for a good quality embryo
• hCG

  Human Chorionic Gonadotrophin
• Monitoring of oocytes by ultrasound and harvesting of oocytes (aspiration)

  Completed transvaginally
• Hormones


  Given to prepare uterus (Progesterone) by injection or vaginally. Oestrogen can also be given
• In Vitro Fertilisation

  1. Aspiration from the ovary is followed by incubation with sperm for 12-16 hours

  2. Evidence of a polar body is indicative of a healthy zygote. This can be collected for preimplantation genetic testing

  3. Viable zygotes cultured for several days (up to 6d), until a healthy blastocyst forms

  4. Transfer to uterus by catheter. Transplantation number is limited by the UK HEFA
• Picture of IVF embryo - this is a fertilized human egg). Male and female genetic material (DNA) are in the 2 pronuclei
• Photo of a high quality day 3 human embryo at the 8-cell stage 6 cells are visible in this plane of focus
• This picture shows a high quality blastocyst embryo on day 5
• Fertilised egg Quality and staging

  • Implant day 5-5.5
  • The ICM must have a reasonable number of cells
  • The trophoblast must have a number of well-connected cells
  • 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. A hollow ball of cells with good trophoblast and Inner Cell Mass (ICM). Removal of trophoblast for PGT
  • Day six: Blastocyst "hatches"
• Blastocyst grading


  • A
  • B
  • C
• These 5-day embryos are at the blastocyst stage. Focus is on ICM on the left and Trophoblast on the right
• Good embryo


  • Lots of nice compacted cells in ICM and the in the good trophoblast there are multiple connected trophoblast cells
• ICM

  The ICM must have a reasonable number of cells
• Trophoblast

  The trophoblast must have a number of well-connected cells
• Blastocyst grading

  • Good
  • Fair
  • Poor