Assisted Reproductive Technology (ART) and Infertility

Infertility

• Definition: Infertility is a condition where a couple is unable to conceive after a year of regular, unprotected sexual intercourse.
• Primary infertility: When a couple has never had a child before.
• Secondary infertility: When a couple has had a child before, but is unable to conceive again.
• Worldwide statistics: 48.5 million couples suffer from infertility.
• Malaysian statistics: Total fertility rate (TFR) declined from 4.9 children per woman in 1970 to 1.7 in 2020.

Causes of Infertility

• General causes:
  • 1/3 female factors
  • 1/3 male factors
  • 1/3 both/unexplained factors
• Age: Decreased fertility by 50% at age 40, more related to female factor.
• Genetic factors
• Health conditions:
  • Diabetes
  • Thyroid
  • STD
  • Cancer
  • Hypothalamic-pituitary factors
• Environmental factors:
  • Pesticides
  • Chemicals
  • Heavy metals
  • Radiation
• Lifestyle:
  • Excessive alcohol intake
  • Smoking
  • Drug abuse
• Medications:
  • Anti-depression
  • NSAIDs
  • Uncertified local products
• Chemotherapy
• Dietary factors:
  • Nutrient deficiencies (selenium, zinc, vit B, C, E)
  • High cholesterol
  • Caffeinated coffee

Female Factors

• Vaginismus
• Tubal factors:
  • History of PID
  • Tubal surgery
  • Previous ectopic pregnancy
• Pelvic causes:
  • Endometriosis
  • Adhesions
• Ovarian disorders:
  • Uterine/cervical factors:
    • Congenital uterine anomaly
    • Aging
    • Diminished ovarian reserve
    • Endocrine disorder
    • PCOS

Male Specific Causes

• Obstruction in male reproductive ducts -> azoospermia
• Hormonal disorders -> abnormalities in hormones produced by pituitary gland, hypothalamus, and testicles
• Varicocele, accessory gland infection, hydrocele
• Psychosexual problem:
  • Erectile dysfunction
  • Premature ejaculation
  • Physical disabilities

Fertility Treatment

• Timed sexual intercourse
• Intrauterine insemination (IUI)
• Assisted Reproductive Technology (ART)
  • In vitro fertilization (IVF)
  • Intracytoplasmic sperm injection (ICSI)
  • Gamete intrafallopian transfer (GIFT)
  • Zygote intrafallopian transfer (ZIFT)
  • Cryopreservation – gametes, embryos
  • Pre-implantation genetic testing (PGT)

Important Steps for IVF or ICSI

• Controlled ovarian stimulation
• Oocyte retrieval
• Embryo freezing
• Oocyte culture
• Embryo transfer
• Oocyte freezing
• Insemination of gametes – IVF or ICSI

Steps for IVF or ICSI

• Step 1: Hormone stimulation
• Step 2: Oocyte retrieval / ovum pick up
• Step 3: Oocyte / ovum / egg culture
• Step 4: Sperm preparation

Sperm Preparation

• Seminal fluid analysis (SFA)
• Sperm DNA fragmentation – not routine
• Sperm preparation for ART

Seminal Fluid Analysis (SFA)

• Abstinence 2-5 days before test
• Obtained by masturbation / coitus interruptus
• Collected in a sterile container
• Do not use lubricant / condom
• Must bring to lab within 45min – 1 hr (kept in body temperature)

Semen Analysis

• Macroscopic:
  • Color: grayish white
  • Liquefaction
  • Viscosity
  • Volume: >1.5ml -5.0ml
  • pH (strips): Slight alkaline >7.0
• Microscopic:
  • Sperm concentration/count
  • Sperm motility
  • Sperm morphology

Sperm Concentration

• Makler chamber
• x 20 objective
• Haemocytometer
• Normal concentration: > 15 x 106/ml (in 10 boxes)
• Total count: Normal concentration x Volume (per ejaculate)

Sperm Motility

• Class 1: rapid progressive motility
• Class 2: slow progress motility
• Class 3: non-progressive motility
• Class 4: immotile (no flagellar activity)
• Total motility: Normal class 1+2>=30%

Sperm Morphology

• Examples of abnormal morphology