Ovarian Stimulation for IVF in Diminished Ovarian Reserve
Use a GnRH antagonist protocol with gonadotropin dosing of 225-300 IU daily, starting on cycle day 2-3, and consider adjunctive growth hormone or DHEA supplementation to maximize oocyte yield in this patient with diminished ovarian reserve. 1
Initial Protocol Selection
GnRH antagonist protocols are the first-line approach for controlled ovarian stimulation, offering flexibility and reduced medication burden compared to long agonist protocols. 1
Start recombinant FSH at 225 IU daily (or up to 300 IU for poor responders) on cycle day 2-3 of the menstrual cycle, with dosing adjusted based on age and ovarian reserve markers. 2
For patients with diminished ovarian reserve (AMH 0.7, FSH 10), higher starting doses are justified to recruit the maximum number of follicles available. 1, 3
TSH Optimization Before Stimulation
- The TSH of 3.5 should be optimized to <2.5 mIU/L before initiating IVF stimulation, as subclinical hypothyroidism can impair oocyte quality and pregnancy outcomes. This is a critical but often overlooked step.
Alternative Protocols for Poor Responders
If standard stimulation yields inadequate response, consider alternative approaches including natural cycle IVF, minimal stimulation protocols, or luteal phase stimulation to increase cumulative oocyte retrieval opportunities. 1
A combined protocol using both urinary FSH (uFSH) and recombinant FSH (rFSH) has demonstrated significantly higher proportions of mature metaphase II oocytes and grade 1 embryos compared to either preparation alone, with higher delivery rates in poor and normal responders. 3
Trigger and Retrieval Strategy
After adequate follicular development, trigger final oocyte maturation with hCG 36-38 hours before transvaginal ultrasound-guided oocyte retrieval. 2
Plan for a freeze-all strategy rather than fresh transfer, as this eliminates OHSS risk and allows for optimal endometrial preparation in a subsequent frozen embryo transfer cycle, which may improve outcomes in diminished ovarian reserve patients. 4
Fertilization and Embryo Management
Use intracytoplasmic sperm injection (ICSI) for all retrieved oocytes to maximize fertilization rates and minimize interference with any future genetic testing. 1, 2
Perform trophectoderm biopsy at the blastocyst stage (day 5-6) if preimplantation genetic testing is desired, with 5-8 cells being optimal for biopsy. 1
Vitrify all resulting embryos for transfer in subsequent optimized frozen embryo transfer cycles. 4
Transfer Strategy
Transfer only one embryo per cycle to avoid multiple pregnancy risks without compromising cumulative live birth rates. 1
Multiple freeze-all cycles may be needed to bank sufficient embryos before proceeding to transfer, given the expected lower oocyte yield with diminished ovarian reserve.
Critical Pitfalls to Avoid
Do not use GnRH agonist long protocols in this patient, as antagonist protocols offer equivalent or superior outcomes with reduced medication burden and duration. 5, 6
Avoid undertreating with low gonadotropin doses in an attempt to be conservative—this patient needs maximal stimulation to recruit her limited follicular cohort. 3
Do not proceed with fresh embryo transfer, as the freeze-all approach eliminates OHSS risk and may improve pregnancy rates by allowing optimal endometrial preparation. 4