What is the recommended starting dose, monitoring protocol, and contraindications for Maragen (recombinant human follicle‑stimulating hormone) in a woman undergoing ovulation induction for intra‑uterine insemination or in vitro fertilisation?

Maragen (Recombinant Human FSH) Therapy for Ovulation Induction

Starting Dose

For ovulation induction in IUI cycles, start with 75 IU or lower of recombinant FSH daily, as higher doses provide similar pregnancy rates but significantly increase multiple pregnancy risk. 1

• The recommended starting dose is 75 IU daily administered subcutaneously, beginning on cycle day 2-3 or after adequate pituitary suppression if using GnRH agonist pre-treatment 1
• For late-start protocols, 75 IU daily from cycle day 7 until the leading follicle reaches >17 mm has demonstrated efficacy with only 8% multiple follicular development compared to 25% with clomiphene 2
• Recombinant FSH has approximately 75% bioavailability via subcutaneous or intramuscular routes, with an apparent terminal half-life of 37±25 hours 3
• The subcutaneous route is preferred over intramuscular administration for patient convenience and equivalent efficacy 3

Monitoring Protocol

Monitor follicular development with transvaginal ultrasound and serum estradiol levels every 2-3 days once stimulation begins, with more frequent monitoring as follicles approach maturity. 1

Ultrasound Monitoring

• Begin ultrasound monitoring on cycle day 7-8 or after 5-6 days of FSH administration 2
• Assess follicle number and size at each visit 1
• The uterine cavity should show smooth endometrial echoes in an uninterrupted shallow Y contour 1

Hormonal Monitoring

• Measure serum estradiol (E2) levels with each ultrasound to confirm appropriate ovarian response 1
• E2 should rise progressively with follicular development 1

Trigger Criteria

• Administer 5,000 IU hCG intramuscularly when at least one follicle reaches ≥17-18 mm mean diameter with appropriately rising E2 1, 4, 5
• Perform IUI 24-40 hours after hCG injection without compromising pregnancy rates 1, 4, 5

Critical Safety Thresholds and Contraindications

Withhold hCG trigger and cancel the IUI cycle when >2 dominant follicles >15 mm OR >5 follicles >10 mm are present to prevent high-order multiple gestations and OHSS. 1, 6, 4

Cycle Cancellation Criteria

• More than 2 follicles >15 mm at time of trigger 1, 6
• More than 5 follicles >10 mm at time of trigger 1, 6
• These thresholds are based on multiple pregnancy risk data showing 6% risk with 2 dominant follicles, 14% with 3 follicles, and 10% with 4 follicles 1, 6

Alternative Management Options

• Aspiration of excess follicles at time of hCG injection may reduce multiple pregnancy risk as an alternative to cycle cancellation 1
• Conversion to IVF with single embryo transfer when excessive follicular response occurs 6

Absolute Contraindications

• Active pelvic infection or untreated sexually transmitted infections 1
• Uncontrolled thyroid or adrenal dysfunction (general medical knowledge)
• Known hypersensitivity to recombinant FSH preparations (general medical knowledge)
• Ovarian, uterine, or breast malignancy (general medical knowledge)

Relative Contraindications

• Baseline ovarian cysts >20 mm (general medical knowledge)
• Significantly elevated baseline FSH indicating poor ovarian reserve (general medical knowledge)

Common Pitfalls to Avoid

• Do NOT use GnRH agonists for triggering in IUI cycles - they increase multiple pregnancy rates and costs without improving pregnancy rates 1, 6
• Do NOT exceed 75 IU daily starting dose - higher doses increase multiple pregnancy risk without improving outcomes 1
• Do NOT proceed with hCG trigger when safety thresholds are exceeded - the risk of high-order multiples and OHSS outweighs potential pregnancy benefit 1, 6, 4
• Do NOT add GnRH agonist to gonadotropin protocols in IUI - this increases costs and multiple pregnancy rates without benefit 1

Alternative Considerations

• Clomiphene citrate (100 mg daily for 5 days) or tamoxifen are acceptable lower-cost alternatives with reduced multiple pregnancy rates, though they yield lower live birth rates than gonadotropins 1, 6
• For patients at high risk of excessive response, consider starting with oral agents before escalating to gonadotropins 1