SH/RU/GU 13: IVF

🌱 1. Female & Male Mechanisms of Infertility

👩‍🦰 Female Infertility – Mechanisms

Most commonly due to ovulatory dysfunction, but can occur at any step of reproduction.

Key causes:

• Defective ovulation (anovulation)

  • Hormonal imbalance (PCOS, hypothalamic dysfunction)

• Diminished ovarian reserve

  • Age-related decline in egg quantity and quality

• Structural causes

  • Fibroids

  • Endometriosis

  • Congenital uterine abnormalities

• Tubal factors

  • Prior infections

  • Pelvic or abdominal surgeries

  • Ectopic pregnancies

• Immune causes

  • Anti-sperm antibodies (ASA)

• Genetic causes

Pathophysiology (high-yield):

• Aging → ↓ ovarian reserve + ↓ oocyte quality

• ↓ AMH = fewer follicles → poorer response to stimulation

• Structural abnormalities → impaired fertilization or implantation

👨‍🦱 Male Infertility – Mechanisms

Key causes:

• Low sperm count

• Defective spermatogenesis

• Anatomical obstruction

• Retrograde ejaculation

• Hormonal abnormalities

  • Low testosterone

  • Pituitary dysfunction (LH/FSH issues)

• Psychosexual dysfunction

  • Erectile or ejaculatory disorders

• Immune causes

  • Anti-sperm antibodies

• Genetic abnormalities

Pathophysiology:

• Impaired sperm production, delivery, or function

• Hormonal dysregulation → ↓ spermatogenesis

🧪 2. Evaluation & Diagnostic Workup (Female & Male)

👩 Female Evaluation

• Hormone evaluation

• Ovulation prediction kits

  • Detect LH surge (fertile window)

• Ovarian reserve testing

  • Anti-Müllerian Hormone (AMH)

    • Reflects quantity, NOT quality of eggs

• Hysterosalpingography (HSG)

  • X-ray + contrast dye

  • Evaluates uterine shape + tubal patency

  • Slight ↑ fertility post-procedure

👨 Male Evaluation

• Semen analysis

• Testosterone levels

• LH testing (pituitary function)

• Genetic testing

• Testicular ultrasound / biopsy

• Anti-sperm antibody testing

🌿 3. Non-Pharmacologic Approaches to Infertility

Natural & Behavioral Approaches

• Timed intercourse

• Natural cycle + IUI (unexplained infertility)

• Biological markers:

  • Menstrual cycle tracking

  • Urinary LH kits

  • Basal body temperature (BBT)

  • Cervical mucus changes

➡ Often tried before medications, or alongside early treatment.

💊 4. Pharmacologic Pro-Fertility Treatments

(MOA, Counselling & Monitoring)

🌼 Ovulation Induction – Oral Agents

Letrozole (Aromatase Inhibitor) – ⭐ FIRST-LINE

Indications:

• Anovulation

• PCOS

• Unexplained infertility

• Fertility preservation (e.g. ER+ breast cancer)

MOA:

• Inhibits aromatase → ↓ estrogen

• ↑ FSH release

• Promotes follicular development

• Preserves normal hypothalamic feedback

Dosing window:

• Days 3–7, 4–8, or 5–9 of cycle

Counselling:

• Off-label use

• Timing of intercourse/IUI is critical

• Possible multiple follicles (but lower than injectables)

Monitoring:

• Ovulation (LH kits)

• Ultrasound follicle tracking if used

• Pregnancy testing

💉 Ovulation Induction – Injectable Gonadotropins

FSH ± LH injections

• Gonal-F, Puregon, Bravelle

• Menopur (FSH + LH)

MOA:

• Direct ovarian stimulation

• Promotes multiple follicle growth

Used when:

• Letrozole fails

• IVF cycles

Counselling:

• Injectable technique

• High risk of multiple gestation

• Requires frequent monitoring

Monitoring:

• Ultrasound follicle count

• Estradiol levels

• Signs of OHSS

⛔ GnRH Agonists & Antagonists

Purpose:
➡ Prevent premature LH surge

Agents:

• GnRH agonist: Leuprolide

• GnRH antagonists: Cetrorelix, Ganirelix

MOA:

• Suppress LH surge

• Allow controlled egg maturation

Counselling:

• Injection timing is critical

• Latex allergy warnings (some products)

🎯 hCG “Trigger Shot”

• Pregnyl, Ovidrel

MOA:

• Mimics LH surge

• Triggers ovulation

Timing:

• Ovulation occurs ~36 hours after injection

VERY time-sensitive

Monitoring & Safety:

• Risk of OHSS

• Injection site reactions

• Systemic hypersensitivity

🌸 Progesterone Support (Luteal Phase)

Purpose:

• Supports endometrial lining

• Improves implantation success

Forms:

• Vaginal gel, tablets, suppositories

• IM injections

Counselling:

• Start after egg retrieval

• Continue until pregnancy test (or up to 10 weeks if pregnant)

• Watch for allergies (peanut oil!)

⚠ Ovarian Hyperstimulation Syndrome (OHSS)

Pathophysiology:

• Excess VEGF → vascular leakage

• Ovarian enlargement + fluid shifts

Symptoms:

• Mild: bloating, nausea, ovarian pain

• Severe:

  • Rapid weight gain

  • Ascites

  • Dyspnea

  • Oliguria

  • Lab abnormalities

• Life-threatening:

  • Thromboembolism

  • Renal failure

  • ARDS

➡ Pharmacists MUST recognize early

💔 5. Psychological & Emotional Challenges of IVF

This is testable and clinically important 💗

Psychological Impact:

• Anxiety:

  • ~50% women, ~33% men at baseline

  • ↑ to ~75% women, ~60% men over time

• Depression:

  • ~25% women, ~10% men initially

  • ↑ with repeated cycles

Key stressors:

• Emotional burden of repeated failure

• Physical stress from injections/procedures

• Financial strain

• No guaranteed success

• Often multiple cycles required (up to 6)

➡ Important pharmacist role:

• Empathy

• Clear counselling

• Setting realistic expectations

• Medication education & reassurance

✨ High-Yield Takeaway

• Infertility is multifactorial

• Treatment escalates: natural → oral → injectables → IVF

• Letrozole = first-line ovulation induction

• hCG timing is CRITICAL

• OHSS is the most serious medication-related risk

• IVF is emotionally, physically, and financially taxing