In a healthy reproductive‑age woman with low anti‑Müllerian hormone undergoing a fresh or frozen embryo transfer, what is the recommended hMG (human menopausal gonadotropin) protocol with added LH activity, including starting dose, timing, monitoring, and risks?

hMG with Added LH Activity in Low AMH Patients Undergoing Embryo Transfer

For reproductive-age women with low AMH undergoing fresh or frozen embryo transfer, hMG (human menopausal gonadotropin) is not the standard protocol—these patients require controlled ovarian stimulation for oocyte retrieval first, not direct embryo transfer preparation. The question appears to conflate two distinct treatment phases: ovarian stimulation for IVF/ICSI versus endometrial preparation for embryo transfer.

Critical Clarification: Treatment Context Matters

The evidence base addresses hMG use during ovarian stimulation cycles (for oocyte retrieval), not embryo transfer cycles 1, 2. Low AMH indicates diminished ovarian reserve, which affects the stimulation phase, not the transfer phase 3, 4.

If the Question Concerns Ovarian Stimulation (Pre-Retrieval):

Starting Dose and Protocol

• Begin with 150-300 IU daily of hMG containing both FSH and LH activity (typically 1:1 ratio of FSH to LH-like activity from hCG) 1, 5.
• Higher starting doses (225-300 IU) are appropriate for women with low AMH given their expected poor ovarian response 2.
• hMG provides endogenous LH activity through its hCG component, which has LH-like effects on the LH receptor 1, 5.

Timing and Administration

• Initiate hMG on cycle day 2-3 after baseline ultrasound confirms no ovarian cysts 2.
• Continue daily subcutaneous injections until trigger criteria are met 1.
• Maximum stimulation duration typically 16 days before reassessing protocol 5.

Monitoring Requirements

• Baseline assessment: Transvaginal ultrasound for antral follicle count, serum FSH, LH, estradiol, and AMH 3, 4.
• During stimulation: Ultrasound monitoring every 2-3 days starting cycle day 6-8 to assess follicular development 2.
• Serial hormone monitoring: Estradiol and LH levels every 2-3 days during mid-to-late stimulation 2, 6.
• Trigger criteria: At least 2-3 follicles ≥17-18mm with appropriate estradiol rise (typically >500-1000 pg/mL total) 5, 6.

LH Supplementation Considerations

• In low AMH patients with adequate baseline LH (>0.5-1.5 IU/L), additional recombinant LH supplementation beyond hMG's inherent LH activity does not improve outcomes and may increase OHSS risk 6.
• However, if mid-cycle LH drops below 0.5 IU/L during stimulation, consider adding recombinant LH 75 IU daily 2, 5.
• The combination of recombinant FSH 150 IU plus recombinant LH 75 IU (2:1 ratio) showed superior pregnancy rates (55.6% vs 23.3%) compared to hMG alone in hypogonadotropic patients 5.

If the Question Concerns Embryo Transfer Preparation:

For Fresh Embryo Transfer

• No hMG is used during fresh transfer cycles—the corpus luteum from the stimulation cycle provides progesterone support 1.
• Luteal phase support uses progesterone supplementation (vaginal or intramuscular), not gonadotropins 1.

For Frozen Embryo Transfer (FET)

• hMG is not part of standard FET protocols 1.
• FET preparation uses either natural cycle monitoring (for ovulatory women) or programmed cycles with exogenous estrogen and progesterone 1.
• Gonadotropins are not administered during FET endometrial preparation 1.

Key Risks and Monitoring

Primary Risks with hMG

• Ovarian hyperstimulation syndrome (OHSS): Risk increases with higher estradiol levels (>2500-3000 pg/mL) and multiple follicles 6.
• Multiple pregnancy: Risk correlates with number of mature follicles; cancel cycle if >2 follicles >15mm in IUI contexts 3, 7.
• Lower fertilization rates: Some evidence suggests hMG supplementation may reduce fertilization rates compared to recombinant FSH alone (69.6% vs 89.1%) 6.

Risk Mitigation Strategies

• Use minimum effective dose—avoid exceeding 300 IU daily starting dose 2, 6.
• Cancel cycle or convert to IVF if excessive follicular response develops 7.
• Consider coasting (withholding gonadotropins while monitoring) if estradiol rises too rapidly 6.
• In high-risk patients, trigger with GnRH agonist instead of hCG to reduce OHSS risk (applicable only in antagonist protocols, not relevant to standard hMG long-agonist protocols) 7.

Special Considerations for Low AMH Patients

• AMH limitations: AMH reflects only the FSH-responsive follicular pool, not the total primordial reserve, and can increase with gonadotropin stimulation 4.
• Low AMH patients often require higher gonadotropin doses but have lower overall success rates per cycle 3, 4.
• Fertility preservation counseling: Women with low AMH should be counseled about risks of delaying childbearing and consider oocyte cryopreservation 3.
• Bone mineral density screening is warranted if hypogonadism is present 3.