What are the treatment options for primary infertility?

Treatment Options for Primary Infertility

The most effective approach to primary infertility is a systematic evaluation of both partners followed by targeted interventions based on identified causes, with treatment options including ovulation induction, intrauterine insemination (IUI), and in vitro fertilization (IVF) depending on specific diagnoses. 1, 2

Initial Diagnostic Evaluation

Female Evaluation

• Medical and reproductive history:

  • Past surgeries and hospitalizations
  • Medical conditions associated with reproductive failure (thyroid disorders, endocrine disorders)
  • Reproductive history (cycle characteristics, pregnancy attempts)
  • Sexual history and STD exposure 1

• Physical examination:

  • Height, weight, BMI calculation
  • Thyroid examination
  • Clinical breast examination
  • Assessment for signs of androgen excess
  • Pelvic examination 1

Male Evaluation

• Medical and reproductive history:

  • Systemic illnesses (diabetes)
  • Prior surgeries and infections
  • Medications and lifestyle exposures
  • Sexual history 1

• Physical examination:

  • Examination of penis and urethral meatus
  • Testicular examination and measurement
  • Assessment of vas deferens and epididymis
  • Presence of varicocele
  • Secondary sex characteristics 1

• Semen analysis: Two samples at least one month apart with assessment of:

  • Volume (normal: 1.5-5.0 ml)
  • pH (normal: >7.2)
  • Sperm concentration (normal: >20 million/ml)
  • Total motile sperm count (normal: >5 million) 2

Treatment Options by Cause

Female Factor Infertility

Ovulatory Dysfunction (25% of cases)

• First-line treatment: Ovulation induction with:
  • Clomiphene citrate or letrozole for 3-6 cycles 3, 4
  • Low-dose gonadotropins (75 IU or lower) if clomiphene fails 1
  • Monitor for multiple follicle development; withhold IUI if >2 follicles >15mm or >5 follicles >10mm 1

Tubal Factor (20% of cases)

• Surgical correction for tubal abnormalities in specialized units
• IVF is indicated for bilateral tubal factor 2, 4

Endometriosis

• Surgical treatment for moderate to severe disease
• IVF for advanced cases or when surgery fails 4, 5

Male Factor Infertility (25% of cases)

Mild Male Factor

• Gonadotropin therapy (HCG with or without FSH) for secondary hypogonadism 2
• Selective Estrogen Receptor Modulators (SERMs) to improve sperm and hormonal parameters 2
• Aromatase Inhibitors to improve hormonal and semen parameters 2
• IUI with ovarian stimulation for mild male factor with total motile sperm count >5 million 1, 2

Severe Male Factor

• IVF with intracytoplasmic sperm injection (ICSI) for severe oligospermia or azoospermia 2
• Microsurgical sperm extraction (micro-TESE) with 55-56% success rate for sperm retrieval 2
• Surgical correction for obstructive azoospermia 2

Unexplained Infertility (25% of cases)

• Initial approach: 3-4 cycles of ovarian stimulation with timed intercourse or IUI 4
• Secondary approach: IVF if initial treatment fails 4

Treatment Algorithm Based on Duration and Age

1. Couples with <35-year-old female partner:

   • Try for 12 months naturally before seeking treatment
   • Begin with less invasive options (lifestyle modifications, ovulation induction)
   • Progress to IUI if initial treatments fail
   • Consider IVF after 3-4 failed IUI cycles 4

2. Couples with 35-38-year-old female partner:

   • Seek treatment after 6 months of trying
   • Consider more aggressive initial approach
   • Limit ovulation induction/IUI cycles to 2-3 before IVF 4

3. Couples with >38-40-year-old female partner:

   • Consider immediate IVF as first-line treatment
   • Success rates decrease significantly with advancing age 2, 4

Lifestyle Modifications

• Weight management: Obesity reduces fertility in both men and women; weight loss improves natural fertility and ART success rates 6
• Smoking cessation: Smoking adversely affects fertility 4
• Moderate alcohol consumption
• Avoidance of excessive testicular heat exposure 2

Important Considerations

• Multiple pregnancy risk: Monitor ovarian stimulation carefully to prevent high-order multiple pregnancies 1
• Ovarian hyperstimulation syndrome: Risk of 1-5% with gonadotropin treatment 4
• Treatment limits: Most guidelines recommend limiting ovulation induction to 6 cycles (including 3 ovulatory cycles) 3
• Cost-effectiveness: For obese women, weight reduction with a hypocaloric diet is the most cost-effective strategy before ART 6

Common Pitfalls to Avoid

1. Delaying treatment in advanced maternal age: Female fertility declines significantly after age 35; immediate IVF may be appropriate for women >38-40 years 2, 4

2. Using testosterone for male infertility: Testosterone therapy inhibits spermatogenesis and should be avoided in men seeking fertility 2

3. Overuse of ART: Many cases of male infertility can be treated with medical or surgical interventions before resorting to ART 7

4. Ignoring lifestyle factors: Addressing modifiable factors like obesity and smoking should be part of initial management 4, 6

5. Continuing ineffective treatments: If no pregnancy occurs after 3-4 IUI cycles, consider moving to IVF 4