What are the implications of a decrease in beta-human chorionic gonadotropin (BHCG) levels from 200 milli-international units (mIU) to 138 mIU between day 12 and day 16 post-blastocyst transfer?

Falling β-hCG After Blastocyst Transfer: Causes and Implications

A decline in β-hCG from 200 mIU/mL on day 12 to 138 mIU/mL on day 16 post-blastocyst transfer indicates a failing pregnancy—this pattern is incompatible with a viable intrauterine pregnancy and most likely represents either an early pregnancy loss or an ectopic pregnancy. 1

Understanding Normal β-hCG Dynamics After Blastocyst Transfer

In viable pregnancies following blastocyst transfer, β-hCG should demonstrate consistent exponential growth:

• Normal viable pregnancies show a β-hCG rise of at least 66% over 48 hours or 120% over 72 hours 2
• The median β-hCG on day 12 after embryo transfer in viable pregnancies is approximately 126 IU/L, compared to 31 IU/L in non-viable pregnancies 3
• By day 16 post-retrieval (approximately day 11 post-blastocyst transfer), β-hCG levels >300 mIU/mL predict ongoing pregnancy in 97% of cases after day 5 blastocyst transfer 4
• Your patient's initial level of 200 mIU/mL on day 12 was already concerning, as it falls below the median for viable pregnancies 3

Primary Causes of Declining β-hCG

1. Early Pregnancy Loss (Most Likely)

• Spontaneous abortion or anembryonic gestation (blighted ovum) accounts for the majority of declining β-hCG patterns in this clinical scenario 2
• In pathologic pregnancies, the mean β-hCG values are significantly lower than ongoing pregnancies at equivalent timepoints 4
• Serial β-hCG measurements showing a decline have 78% sensitivity for detecting pathologic pregnancies 2

2. Ectopic Pregnancy (Critical to Exclude)

• Approximately 22% of ectopic pregnancies present with β-hCG levels below 1,000 mIU/mL, and declining β-hCG does not exclude ectopic pregnancy 1, 5
• The mean β-hCG in ectopic pregnancies at presentation is approximately 1,147 mIU/mL, but ectopic pregnancies can occur at any β-hCG level 1
• Ectopic pregnancy can rupture even with low or declining β-hCG levels, making urgent evaluation mandatory 5

3. Biochemical Pregnancy

• Very early pregnancy loss where β-hCG rises transiently above 5 IU/L but fails to establish a viable pregnancy 3
• This represents the mildest form of pregnancy failure in the spectrum of non-viable pregnancies 3

Immediate Management Algorithm

Step 1: Urgent Transvaginal Ultrasound

Perform transvaginal ultrasound immediately, regardless of the β-hCG level, as approximately 36% of confirmed ectopic pregnancies present with β-hCG <1,000 mIU/mL 5

Key ultrasound findings to assess:

• Presence or absence of intrauterine gestational sac (should be visible at β-hCG >1,000-3,000 mIU/mL) 1
• Adnexal masses or extraovarian findings (positive likelihood ratio of 111 for ectopic pregnancy when no intrauterine pregnancy is present) 5
• Free fluid in the pelvis, especially echogenic fluid suggesting blood 5
• Endometrial thickness (<8 mm virtually excludes normal intrauterine pregnancy; ≥25 mm virtually excludes ectopic pregnancy) 5

Step 2: Repeat β-hCG in 48 Hours

Obtain repeat serum β-hCG exactly 48 hours after the day 16 measurement to confirm declining trend 1

Expected patterns:

• Declining β-hCG confirms non-viable pregnancy; continue monitoring until β-hCG reaches zero 1
• If β-hCG plateaus (defined as <15% change over 48 hours for two consecutive measurements), further evaluation is needed 1
• Any rise in β-hCG, even if suboptimal, requires continued surveillance for ectopic pregnancy 1

Step 3: Clinical Assessment for Ectopic Pregnancy

Evaluate for symptoms requiring immediate intervention:

• Unilateral adnexal tenderness (present in 70-80% of ectopic pregnancies) 5
• Shoulder pain (may indicate ruptured ectopic pregnancy with hemoperitoneum) 1
• Hemodynamic instability (requires emergent surgical consultation regardless of β-hCG level) 5
• Peritoneal signs on examination (requires immediate evaluation) 1

Factors That May Influence β-hCG Levels

While these factors affect absolute β-hCG values, they do not explain a declining pattern:

• Body weight: A 100 lb (45.4 kg) difference in weight is associated with a 34.8% reduction in β-hCG levels, but this affects the absolute value, not the trajectory 6
• Embryo quality: Lower embryo quality is associated with lower β-hCG levels but should still show rising trend if viable 6
• Male factor infertility with ICSI: Associated with relatively low but still rising β-hCG values in viable pregnancies (median 88 IU/L) 3

Critical Pitfalls to Avoid

• Never defer ultrasound based on "low" β-hCG levels in symptomatic patients, as ectopic pregnancies can rupture at any β-hCG level 5
• Do not use β-hCG value alone to exclude ectopic pregnancy in patients with indeterminate ultrasound findings 1, 5
• Never discharge a patient with declining β-hCG without ensuring reliable follow-up and excluding ectopic pregnancy 5
• Do not assume declining β-hCG automatically means intrauterine pregnancy loss without ultrasound confirmation 1

Prognosis and Counseling

With an initial β-hCG of 200 mIU/mL on day 12 and subsequent decline to 138 mIU/mL, the probability of viable pregnancy is essentially zero 3, 4:

• The cut-off value of 76 IU/L on day 12 after embryo transfer emerged as the most suitable threshold to predict viable pregnancy, with your patient's value of 200 mIU/mL being above this but still showing a declining pattern 3
• Mean β-hCG values on day 16 post-retrieval in spontaneous abortions are significantly lower than ongoing pregnancies 4
• The declining trajectory over 4 days confirms non-viability regardless of the absolute values 2