What is the recommended protocol for a patient undergoing fertility treatment with Follitropin (FSH), considering her medical history and potential risks such as ovarian hyperstimulation syndrome (OHSS)?

Follitropin Protocol for Fertility Treatment with OHSS Risk Mitigation

For patients undergoing fertility treatment with Follitropin (FSH), start with individualized dosing based on ovarian reserve markers (AMH, baseline FSH) rather than fixed protocols, use low-dose hCG (2,500-5,000 IU) for final oocyte maturation in high-risk patients, and implement prophylactic anticoagulation if antiphospholipid antibodies are present.

Initial Assessment and Risk Stratification

Before initiating Follitropin therapy, assess OHSS risk factors through:

• Baseline hormone evaluation: Measure FSH, LH, and estradiol on cycle day 3 to assess ovarian reserve and pituitary function 1
• Anti-Müllerian hormone (AMH) testing: Can be measured on any cycle day and serves as the strongest predictor of ovarian response; patients in the highest AMH quartile have significantly elevated OHSS risk 1, 2
• Medical history screening: Identify polycystic ovary syndrome, prior OHSS episodes, and antiphospholipid antibody status 3, 4

Dosing Protocol Selection

For Anovulatory Women (Ovulation Induction)

• Starting dose: 50 IU Follitropin subcutaneously daily for at least 7 days 3
• Dose adjustments: Increase by 25-50 IU at weekly intervals based on follicular growth via ultrasound and serum estradiol monitoring 3
• Trigger criteria: Administer hCG only when acceptable pre-ovulatory state is achieved (adequate follicular development with appropriate estradiol levels) 3

For Normal Ovulatory Women (IVF/ICSI Cycles)

• Starting dose: 200 IU Follitropin subcutaneously daily for at least 7 days 3
• Individualized approach: For high responders (elevated AMH, young age), consider dose reduction from day 6 onward based on ovarian response to minimize OHSS risk 3, 2
• Monitoring: Serial ultrasound evaluation of follicular growth and serum estradiol measurements are essential 3

OHSS Prevention Strategies

Modified hCG Dosing for High-Risk Patients

The most critical intervention for preventing OHSS in high-risk women is reducing the hCG trigger dose:

• Low-dose protocol: Use 2,500 IU hCG instead of the standard 5,000-10,000 IU for final oocyte maturation in patients at high risk of OHSS 4
• Evidence: This approach prevents moderate/severe OHSS without compromising pregnancy rates (61.9% conception rate with low-dose hCG) 4
• Standard dosing: For average-risk patients, use 5,000-10,000 IU hCG when at least three follicles reach >17 mm with appropriately rising estradiol 5, 3

Withholding hCG When Necessary

• Absolute contraindication: If ovaries are abnormally enlarged on the last day of Follitropin therapy, do NOT administer hCG to reduce OHSS risk 3
• Intercourse prohibition: Prohibit intercourse in patients with significant ovarian enlargement after ovulation due to risk of hemoperitoneum from ruptured ovarian cysts 3

Individualized Dosing Reduces OHSS Risk

• Follitropin delta advantage: Individualized dosing with follitropin delta (based on AMH and body weight) significantly reduces moderate/severe OHSS and need for preventive interventions compared to conventional fixed-dose follitropin alfa (p=0.018) 2
• Greatest benefit: Patients in the highest AMH quartile derive the most significant OHSS risk reduction from individualized dosing (p=0.012) 2

Special Population: Antiphospholipid Antibody-Positive Patients

These patients face life-threatening thrombosis risk from elevated estrogen during ovarian stimulation and require mandatory anticoagulation:

• Prophylactic anticoagulation: Start enoxaparin 40 mg subcutaneously daily at the beginning of ovarian stimulation 6, 5
• Peri-retrieval management: Withhold LMWH 24-36 hours before oocyte retrieval, then resume after retrieval 6, 5
• Duration: Continue LMWH until estrogen levels return to near-physiologic levels if no pregnancy occurs 6, 5
• Thrombotic APS: Patients with history of thrombosis require therapeutic-dose LMWH (enoxaparin 1 mg/kg subcutaneously every 12 hours) throughout the ART cycle 6

Monitoring During Treatment

Essential Surveillance Parameters

• Ultrasound monitoring: Serial transvaginal ultrasounds to assess follicular development and detect abnormal ovarian enlargement 3
• Estradiol levels: Frequent serum estradiol measurements to identify excessive ovarian response 3
• OHSS warning signs: Severe pelvic pain, nausea, vomiting, weight gain, abdominal distension 3

Clinical Evaluation Frequency

• During stimulation: Monitor every 2-3 days with ultrasound and estradiol once follicles reach 10-12 mm 3
• Post-hCG: Assess for OHSS development for at least two weeks after hCG administration, as OHSS typically develops 7-10 days post-treatment 3

Contraindications to Follitropin Therapy

Absolute contraindications include 3:

• Prior hypersensitivity to recombinant FSH products
• High FSH levels indicating primary gonadal failure
• Pregnancy
• Uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders)
• Tumors of reproductive organs or hypothalamic-pituitary axis
• Heavy or irregular vaginal bleeding of undetermined origin
• Ovarian cysts or enlargement not due to PCOS

OHSS Management if It Develops

Recognition and Severity Assessment

Early warning signs 3:

• Severe pelvic pain, nausea, vomiting, rapid weight gain
• Abdominal distension and gastrointestinal symptoms
• Dyspnea and oliguria

Severe OHSS features 3:

• Hypovolemia, hemoconcentration, electrolyte imbalances
• Ascites, pleural effusions, pericardial effusion
• Thromboembolic complications

Treatment Approach

• Immediate action: Stop all gonadotropins including hCG; consider hospitalization for serious OHSS 3
• Acute phase management: Limited IV fluids, electrolytes, and human serum albumin to normalize electrolytes while maintaining somewhat reduced intravascular volume 3
• Avoid diuretics: Do not use diuretics in acute phase as they can accentuate diminished intravascular volume 3
• Conservative surgical approach: If bleeding requires intervention, control bleeding while preserving maximum ovarian tissue 3

Common Pitfalls to Avoid

• Fixed dosing in high responders: Using standard 5,000-10,000 IU hCG in patients with elevated AMH or excessive follicular response dramatically increases OHSS risk 4, 2
• Inadequate monitoring: Failure to perform serial ultrasounds and estradiol measurements can miss early signs of overstimulation 3
• Ignoring thrombosis risk: Not implementing anticoagulation in aPL-positive patients during ovarian stimulation can result in life-threatening thromboembolism 6, 5
• Premature fluid correction: Full correction of intravascular volume deficit in acute OHSS leads to unacceptable third-space fluid accumulation 3
• Device errors: Multi-use follitropin pens have higher critical error rates (40-49%) compared to single-use pens (4-7%), particularly with priming and dose verification 7