What are the potential side effects and adverse effects of Menopur (menotropin) in women with infertility due to anovulation or unexplained infertility?

Side Effects and Adverse Effects of Menopur (Menotropin)

Menopur carries significant risks including ovarian hyperstimulation syndrome (OHSS) in 6.2% of IVF cycles, multiple pregnancy rates up to 36%, and serious thromboembolic complications that can be life-threatening. 1, 2

Common Side Effects (≥2% Incidence)

The most frequently reported adverse effects from clinical trials include:

• Abdominal symptoms: Abdominal pain (6.7%), abdominal cramps (3.0%), and abdominal enlargement (2.3%) 1
• Injection site reactions: Pain and inflammation at injection sites (3.9% combined), with injection site pain being the most frequently reported postmarketing reaction 1
• Headache: Occurs in 6.2% of patients 1
• Nausea: Commonly reported, particularly when combined with other gonadotropins (≥5% incidence) 1

Serious Adverse Effects Requiring Immediate Medical Attention

Ovarian Hyperstimulation Syndrome (OHSS)

OHSS represents the most critical complication, occurring in 6.2% of IVF cycles and 1-5% of all gonadotropin cycles. 1, 2

OHSS manifests with:

• Severe pelvic or abdominal pain
• Sudden weight gain and abdominal swelling
• Nausea, vomiting, and diarrhea
• Decreased or absent urination
• Fluid accumulation in abdomen and chest 1

Stop Menopur immediately and seek emergency care if these symptoms develop, as OHSS can progress to life-threatening complications including respiratory failure and death. 1

Pulmonary and Cardiovascular Complications

• Thromboembolic events: Blood clots can form in blood vessels, leading to stroke, pulmonary embolism, or limb loss 1
• Respiratory complications: Atelectasis, acute respiratory distress syndrome, fluid in lungs, and exacerbation of asthma have been reported 1
• Thrombophlebitis: Reported in <1% of subjects in clinical trials 1

Ovarian Complications

• Abnormal ovarian enlargement: Can cause bloating and severe pelvic pain; patients may need to abstain from intercourse to prevent ovarian cyst rupture 1
• Ovarian torsion: Twisting of the ovary can cut off blood supply, particularly in patients with OHSS, pregnancy, or previous abdominal surgery 1
• Ovarian cysts: Reported in postmarketing surveillance 1

Pregnancy-Related Risks

Multiple Gestation

Multiple pregnancy occurs in up to 36% of gonadotropin cycles, substantially increasing health risks for both mother and babies. 2

This represents a major morbidity concern as multiple gestations carry:

• Increased maternal complications
• Higher perinatal mortality
• Greater healthcare costs 2

Other Pregnancy Complications

• Ectopic pregnancy: Risk increases, especially in women with pre-existing fallopian tube problems 1
• Spontaneous abortion: Risk of early pregnancy loss is elevated, occurring in 21% in one study of PCO patients 3
• Congenital malformations: Babies born after assisted reproductive technology may have increased risk of birth defects, influenced by maternal age, sperm quality, genetic background, and multiple gestation 1

Additional Postmarketing Adverse Reactions

The following have been reported but frequency cannot be reliably determined:

• Gastrointestinal: Abdominal pain (lower), distension, vomiting, discomfort 1
• Neurological: Dizziness in addition to headache 1
• Reproductive: Pelvic pain, breast complaints (pain, tenderness, discomfort, swelling) 1
• Dermatological: Acne and rash 1
• Vascular: Hot flushes 1
• General: Fatigue 1

Long-Term Safety Concerns

Women who use medicines like Menopur multiple times to achieve pregnancy may have an increased risk of ovarian tumors, including cancer. 1

This represents a critical quality-of-life and mortality consideration for patients requiring repeated treatment cycles.

Clinical Context and Risk Mitigation

Research demonstrates that low-dose protocols (112.5 IU/day) in high-risk patients with elevated AMH levels reduced OHSS incidence to 2.6%, with only 2 cycle cancellations required 4. This suggests dose adjustment based on patient characteristics can significantly improve safety profiles.

In anovulatory women with polycystic ovary syndrome, menotropin therapy after clomiphene failure achieved conception in 58% of patients, but with 36% twin pregnancy rate and 21% spontaneous abortion rate. 3 These figures underscore the balance between efficacy and adverse outcomes that must be discussed with patients.