What are the diagnostic and treatment approaches for infertility?

Diagnostic and Treatment Approaches for Infertility

For optimal outcomes in terms of morbidity, mortality, and quality of life, infertility evaluation should include concurrent assessment of both male and female partners, as approximately 50% of infertility cases involve male factors. 1

Initial Evaluation

Female Evaluation

• Comprehensive reproductive history including menstrual cycle characteristics, previous pregnancies, and sexual history 2
• Physical examination focusing on thyroid, breast, and pelvic areas to identify potential causes 2
• Assessment of ovulation through serum progesterone levels at cycle day 21 3
• Evaluation of uterus and fallopian tubes via hysterosalpingography in women without risk factors for obstruction 3
• More advanced imaging (hysteroscopy, laparoscopy, or MRI) for women with history of endometriosis, pelvic infections, or ectopic pregnancy 4

Male Evaluation

• Reproductive history focusing on childhood illnesses, systemic diseases, sexual function, and medication use 2
• Physical examination including assessment of penis, testes measurement, evaluation of vas deferens and epididymides, checking for varicocele, and digital rectal examination 2
• Semen analysis as the cornerstone diagnostic test, with parameters including volume, pH, concentration, motility, and morphology 1
• Men with abnormal semen parameters should be referred to a male reproductive specialist for further evaluation 1

Common Causes of Infertility

• Female factors (40-50%): ovulatory dysfunction, tubal disease, uterine abnormalities, endometriosis 5, 4
• Male factors (30-35%): abnormal sperm parameters, hormonal disorders, genetic abnormalities 5, 6
• Combined male and female factors (20-30%) 6
• Unexplained infertility (15%) despite thorough evaluation 5

Treatment Approaches

Female Factor Infertility

• Ovulatory dysfunction:
  • First-line treatment with ovulation induction using clomiphene citrate or letrozole 7, 5
  • Gonadotropins may be used if first-line treatments fail 5
  • Monitor for multiple pregnancy (up to 36% of cycles) and ovarian hyperstimulation syndrome (1-5% of cycles) 5

Male Factor Infertility

• Hormonal treatments:

  • Avoid testosterone monotherapy as it suppresses spermatogenesis 1
  • Consider aromatase inhibitors, human chorionic gonadotropin, or selective estrogen receptor modulators for men with low testosterone 1
  • FSH analogues may improve sperm concentration and pregnancy rates in idiopathic infertility 1

• Surgical interventions:

  • Microsurgical reconstruction for obstructive azoospermia 1
  • Microdissection-testicular sperm extraction (micro-TESE) for non-obstructive azoospermia, which has 1.5 times higher success rates than conventional sperm extraction 1
  • Transurethral resection of ejaculatory ducts for ejaculatory duct obstruction 1

Assisted Reproductive Technologies

• Intrauterine insemination (IUI):

  • Appropriate for mild male factor, unexplained infertility, or cervical factors 5
  • Limited success with total motile sperm count <5 million 1

• In vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI):

  • Indicated for severe male factor infertility, bilateral tubal obstruction, or failed other treatments 5
  • Consider as first-line treatment for women over 38-40 years due to declining fertility with age 5
  • ICSI can overcome most sperm quality issues as long as viable sperm are available 1

Special Considerations

• Health implications beyond fertility:

  • Men with abnormal semen parameters have higher rates of testicular cancer 1
  • Men with azoospermia have higher rates of cancer in general 1
  • Advanced paternal age increases risk of genetic mutations and conditions in offspring 1

• Lifestyle modifications:

  • Weight loss for obese patients 4
  • Smoking cessation and limiting alcohol intake 4
  • Avoiding gonadotoxic medications and environmental exposures 1, 4

Treatment Algorithm

1. Identify specific cause(s) of infertility through comprehensive evaluation 1
2. Address correctable factors (hormonal imbalances, anatomical issues) 1
3. For ovulatory dysfunction: Begin with ovulation induction and timed intercourse 5
4. For unexplained infertility, endometriosis, or mild male factor: Try 3-4 cycles of ovarian stimulation with IUI 5
5. For severe male factor, bilateral tubal obstruction, or failed previous treatments: Proceed to IVF with or without ICSI 1, 5
6. Consider immediate IVF for women over 38-40 years due to age-related fertility decline 5

Common Pitfalls to Avoid

• Delaying evaluation beyond 12 months (or 6 months for women >35 years) 4
• Treating the female partner without evaluating the male 1
• Using testosterone therapy for male infertility, which suppresses spermatogenesis 1
• Relying solely on semen analysis without further male evaluation when abnormalities are found 6
• Proceeding directly to expensive ART without identifying and addressing correctable causes 6
• Overlooking the health implications of infertility beyond reproduction 1