Initial Approach for Infertility Treatment Protocol
For couples with unexplained infertility or mild male factor infertility, intrauterine insemination with ovarian stimulation (IUI-OS) is recommended as the initial treatment approach, followed by IVF after three unsuccessful cycles. 1
Diagnostic Evaluation Before Treatment
Female Partner Assessment:
- Complete reproductive history including:
- Duration of attempting pregnancy
- Menstrual cycle characteristics (length, regularity)
- Previous pregnancies and outcomes
- Age at menarche and dysmenorrhea history
- Previous STIs or pelvic inflammatory disease 1
- Physical examination focusing on:
- BMI calculation (both very low and high BMI reduce fertility)
- Thyroid examination
- Signs of androgen excess
- Pelvic examination to assess reproductive organs 1
Male Partner Assessment:
- Concurrent evaluation is essential (both partners should be assessed simultaneously) 1
- Complete reproductive history
- Semen analysis (1-3 samples) as the cornerstone of evaluation 1
- Men with abnormal semen parameters should be evaluated by a male reproductive expert 1
- Consider evaluation of male partner in cases of recurrent pregnancy loss or failed ART cycles 1
Treatment Protocol Algorithm
Step 1: Lifestyle Modifications
- Educate about peak fertility days and signs (cervical mucus changes)
- Recommend intercourse every 1-2 days beginning after menstruation
- Consider ovulation prediction methods (kits, apps, cycle beads)
- Discourage smoking, alcohol, recreational drugs, and most commercial lubricants
- Recommend weight optimization if BMI is very low or high
- Reduce caffeine intake if excessive (>5 cups/day) 1
Step 2: Initial Treatment for Unexplained or Mild Male Factor Infertility
- First-line therapy: IUI with ovarian stimulation 1
Step 3: Treatment Progression
- If not pregnant after three cycles of clomiphene citrate-IUI, proceed directly to IVF 1
- This approach is most cost-effective and minimizes time to pregnancy 1
Special Considerations
Male Factor Infertility Treatment:
- For hypogonadotropic hypogonadism with desire to preserve fertility:
- Consider selective estrogen receptor modulators (SERMs) like clomiphene citrate
- Starting dose: 25mg every other day
- Monitor response and continue for up to 6 treatment cycles if responding
- Consider alternative approaches if no improvement after 3 months 2
- Note: SERMs have limited benefits compared to ART with pregnancy rates around 26% 2, 3
Age-Based Considerations:
- For women >35 years, consider earlier evaluation (after 6 months of trying) 1
- For women >38-40 years, consider immediate IVF as first-line treatment due to declining fertility 4
Treatment Selection Based on Diagnosis:
- Anovulatory disorders: Ovulation induction with timed intercourse
- Unexplained infertility/mild male factor: 3-4 cycles of IUI-OS, then IVF
- Severe male factor or bilateral tubal factor: Immediate IVF 4
Important Cautions
- Multiple pregnancy risk: Monitor ovarian stimulation carefully to prevent high-order multiples 1
- Ovarian hyperstimulation syndrome risk: 1-5% of gonadotropin cycles 4
- Limit clomiphene citrate treatment to maximum 12 cycles due to potential ovarian tumor risk 5
- Screen couples for infectious diseases according to local regulations before treatment 1
Treatment Efficacy
- IUI-OS is non-inferior to IVF strategies for mild male factor and unexplained infertility 1
- IUI-OS is more cost-effective than IVF without being significantly less effective 1
- Clomiphene citrate increases sperm concentration and motility in men with idiopathic infertility 3
- Pregnancy rates with clomiphene for male infertility average 17% (range 0-40%) 3
By following this protocol, most couples with infertility can achieve pregnancy through a systematic approach that balances effectiveness, cost, and safety considerations.