What is the recommended dosage and treatment protocol for Menopur (menotropin) injection in women with infertility due to anovulation or unexplained infertility?

Menopur (Menotropin) Injection for Infertility Treatment

Recommended Dosage and Protocol

For women undergoing assisted reproductive technology (ART) cycles, the FDA-approved initial dose of Menopur is 225 International Units (IU) administered subcutaneously daily, starting on cycle day 2 or 3 after pituitary suppression with a GnRH agonist. 1

Starting Dose and Administration

• Begin with 225 IU subcutaneously daily in the abdomen starting on cycle day 2 or 3 of the menstrual cycle 1
• Menopur may be co-administered with Bravelle (urofollitropin), with a combined total initial dose not exceeding 225 IU (e.g., 150 IU Menopur + 75 IU Bravelle, or 75 IU Menopur + 150 IU Bravelle) 1
• The subcutaneous route causes significantly fewer injection site reactions compared to other formulations 2

Dose Adjustments

• Make the first dose adjustment after 5 days based on ovarian response as determined by ultrasound evaluation of follicular growth and serum estradiol levels 1
• Do not adjust doses more frequently than every 2 days 1
• Do not increase by more than 150 IU at each adjustment 1
• Maximum daily dose is 450 IU—do not exceed this threshold 1
• Maximum treatment duration is 20 days 1

Special Populations: High AMH Patients

For women with high anti-Müllerian hormone (AMH) levels (>32 pmol/L) who are at increased risk of ovarian hyperstimulation syndrome (OHSS):

• Consider starting with a lower dose of 112.5 IU/day of highly purified menotropin 3
• This low-dose protocol achieved appropriate ovarian response (5-14 oocytes) in 67.8% of patients with high AMH 3
• The number of oocytes retrieved was inversely related to body weight, so consider higher doses in women with elevated BMI 3
• This approach resulted in only 2.6% OHSS rate 3

Ovulation Induction for Anovulatory Infertility

For women with WHO type II anovulation (typically polycystic ovary syndrome) who have failed clomiphene citrate:

• Use a chronic low-dose protocol with small dose increments to reduce the risk of multiple follicular development and OHSS 4
• Menopur appears to be associated with a less pronounced follicular response and lower risk of ovarian overstimulation compared to recombinant FSH 5
• For WHO type I anovulation (hypogonadotropic hypogonadism), an exogenous supply of LH is required, making Menopur (which contains both FSH and LH activity) an appropriate choice 4

Treatment Context: When to Use Menopur

First-Line Treatment Recommendations

For women with unexplained infertility or mild male factor infertility (total motile sperm count >10 million), intrauterine insemination (IUI) with ovarian stimulation should be the first-line treatment before proceeding to IVF. 6, 7

• At least 3 consecutive IUI cycles with ovarian stimulation should be performed before transitioning to IVF/ICSI 6, 7
• Clomiphene citrate is the preferred first-line agent for IUI cycles due to cost-effectiveness 6
• Gonadotropins (including Menopur) yield significantly higher pregnancy rates than clomiphene citrate (OR = 1.8,95% CI 1.2–2.7) but should be reserved for cases where clomiphene fails or when moving to IVF 7

When to Proceed Directly to IVF with Menopur

• Women with unexplained infertility who have completed 3 cycles of clomiphene-IUI without success should move directly to IVF as the most cost-effective approach 6
• Women over age 38 should proceed more quickly to IVF due to declining ovarian reserve 8
• When IVF with elective single embryo transfer achieves ongoing pregnancy rates exceeding 38%, it becomes preferable to IUI with ovarian stimulation 7

Critical Safety Parameters and Cycle Cancellation Criteria

Preventing Multiple Pregnancy

Withhold hCG administration and cancel the cycle when more than 2 dominant follicles >15 mm or more than 5 follicles >10 mm are present at the time of planned hCG trigger. 7, 1

• This strict cancellation criterion is essential to prevent high-order multiple pregnancies 6, 7
• Multiple pregnancy risk with gonadotropin stimulation is 10-20% without proper cycle management 7
• The goal is to achieve exactly 2 mature follicles (>15mm) to balance success against multiple pregnancy risk 7
• Compared to one dominant follicle, pregnancy rates increase by 5%, 8%, and 8% with two, three, or four dominant follicles, respectively, but multiple pregnancy risk increases to 6%, 14%, and 10% respectively 7

OHSS Prevention

• Withhold hCG administration if ovarian monitoring suggests increased risk of OHSS on the last day of Menopur therapy 1
• Consider GnRH agonist triggering instead of hCG in high-risk patients 3
• Women with high AMH levels (>32 pmol/L) are at particularly increased risk and should be monitored closely 3

Common Pitfalls to Avoid

• Do not use doses higher than 75 IU/day as a starting dose for IUI cycles, as higher doses yield similar pregnancy rates but significantly increase multiple pregnancy risk 7
• Do not add GnRH agonists to gonadotropins for IUI, as they increase multiple pregnancy rates and costs without improving pregnancy rates 7
• Do not proceed with insemination when >2 follicles >15mm develop, as this dramatically increases high-order multiple pregnancy risk without proportional benefit 7
• Do not use Menopur in pregnant women—it is Pregnancy Category X and contraindicated 1

Pre-Treatment Requirements

Before initiating Menopur treatment, the following must be completed 1:

• Complete gynecologic and endocrinologic evaluation
• Diagnosis of the cause of infertility
• Exclusion of pregnancy
• Evaluation of male partner's fertility status
• Exclusion of primary ovarian failure (high FSH levels contraindicate use)
• Screening for infectious agents based on local standards 6

Contraindications

Menopur is contraindicated in women with 1:

• Prior hypersensitivity to menotropins or excipients
• High FSH levels indicating primary ovarian failure
• Pregnancy
• Uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders)
• Sex hormone-dependent tumors
• Pituitary or hypothalamic tumors
• Abnormal uterine bleeding of undetermined origin
• Ovarian cyst or enlargement of undetermined origin (not due to PCOS)

Monitoring Requirements

Menopur should only be used by physicians experienced in infertility treatment with appropriate monitoring facilities available. 1

• Serial transvaginal ultrasound to assess follicular development 1, 3
• Serum estradiol levels 1, 3
• Monitoring should occur after 5 days of treatment and then every 2 days as needed 1

Expected Outcomes

IVF Success Rates

• IVF with Menopur achieves approximately 37% live birth rate per initiated cycle in women of reproductive age 8
• Success rates decline progressively after age 35 8
• Menopur is as effective as recombinant FSH in terms of pregnancy rates, despite being associated with lower oocyte yield 5
• Menopur may improve some aspects of embryo quality in IVF settings 5

Cost-Effectiveness

• For couples with unexplained infertility and TMSC >10 million with prognosis of pregnancy without assistance <30% within a year, at least 3 cycles of IUI with ovarian stimulation is the most cost-effective option before proceeding to IVF 7
• IUI with ovarian stimulation is more cost-effective than proceeding directly to IVF, particularly when strict cancellation criteria minimize multiple pregnancies 7