Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

Area of Science:

• Reproductive Endocrinology and Infertility
• Assisted Reproductive Technologies (ART)
• Clinical Trial Research

Background:

• Excessive response to controlled ovarian stimulation (COS) in IVF/ICSI can lead to cycle cancellation, OHSS, and reduced live birth rates.
• Ovarian reserve tests (ORTs) can predict COS response, but consensus on ORT-based FSH dosing for predicted hyper-responders is lacking.
• Optimizing FSH dosage is crucial for balancing effectiveness and safety in IVF/ICSI cycles.

Purpose of the Study:

• To investigate if a reduced FSH dose in women with a predicted hyper response (high antral follicle count, AFC) affects cumulative live birth rates and safety during IVF/ICSI.
• To compare the effectiveness and safety of a reduced FSH dose (100 IU/day) versus a standard dose (150 IU/day) in predicted hyper-responders.

Main Methods:

• An open-label, multicenter randomized controlled trial (RCT) involving 521 women with regular cycles and AFC > 15, excluding those with PCOS.
• Participants were randomized to receive either 100 IU or 150 IU of FSH daily, with allowed dose adjustments in subsequent cycles.
• The primary outcome was cumulative live birth rate within 18 months; secondary outcomes included OHSS occurrence and cost-effectiveness.

Main Results:

• Cumulative live birth rates were similar between the reduced (66.3%) and standard (69.5%) FSH dose groups (RR 0.95; P=0.423).
• The occurrence of any grade of OHSS was significantly lower in the reduced FSH dose group (5.2% vs. 11.8%; P=0.001).
• Severe OHSS rates did not differ between groups (1.3% vs. 1.1%; P=0.728), and cost-effectiveness analysis showed no dominant strategy.

Conclusions:

• A reduced FSH dose in predicted hyper-responders undergoing IVF/ICSI leads to similar live birth rates compared to a standard dose.
• Lowering FSH dose effectively reduces the incidence of mild and moderate OHSS without impacting severe OHSS rates.
• Future research should focus on safety management strategies and be powered for clinically relevant safety outcomes while assessing non-inferiority for live birth rates.