Is beta human chorionic gonadotropin (β-hcg) rise associated with placental pathology following in vitro fertilization (ivf)-conceived singleton livebirths?

To investigate whether the rate at which beta human chorionic gonadotropin (β-HCG) rises after in vitro fertilization (IVF)/single embryo transfer (SET) is associated with impaired placentation. Design: Retrospective cohort. Setting: Academic fertility center. Patients: 226 livebirths following single ET. Intervention: β-HCG rise [expressed as percentage (%) of initial β-HCG level: (β-HCG2 minus β-HCG1)x100/β-HCG1]. Outcomes: Primary: Placental pathology (abnormalities classified as: anatomic, inflammatory, infectious, and vascular). Secondary: Placental weight (PW in grams). Statistics: Odds ratios (OR), beta coefficients (β), and their respective 95% confidence intervals (95%CI) were calculated using generalized estimating equations regression analysis, adjusted for potential confounders (maternal age, body mass index, infertility diagnosis, fresh vs. frozen ET, hypertensive disorders of pregnancy, gestational age at birth, and infant gender). A subanalysis was performed further stratifying by fresh and frozen ET. β-HCG rise was analyzed both as a linear variable and in quartiles (Q1-Q4). Mean±SD rise in β-HCG (between days 12 and 14 post SET) was 795.4±580.5 IU/L (143.2±49.2%) and quartiles 1-4 were 114.5%-164.2%. Overall, placental pathology rates did not differ between quartiles (Anatomic: 77.2%, 64.3%, 67.9%, and 77.2%, p=0.306; Inflammatory: 21.1%, 16.1%, 26.8%, and 19.3%, p=0.560; Infectious: 28.1%, 37.5%, 28.6%, and 22.8%, p=0.386; Vascular: 68.4%, 60.7%, 76.8%, and 75.4%, p=0.220; for Q1-4, respectively). Mean±SD PW (in grs) was lower in Q1 compared to Q2-Q4 (421.2±119.4, 486.2±123.9, 457.4±114.0, and 442.4±132.4, p=0.044 for Q1 vs. Q2, Q3, and Q4, respectively). After adjustments, there were no differences in either placental pathology or PW, except only for higher PW in Q2 compared to Q1 [adjβ(95%CI): 50.20(6.10, 94.30)]. When analysis was limited to fresh SET, we noted a trend for higher rate of vascular abnormalities among pregnancies with a steeper β-HCG rise [adjOR(95%CI): 1.22(1.01, 1.46), Q4 vs. Q1; 1.002(1.000, 1.003), p=0.006; % HCG rise as linear]. PW results were also similar with the main analysis [adjβ(95%CI): 47.64(0.16, 95.12); for Q2 vs. Q1]. Among the smaller group of frozen SET (N=57), there were no significant differences for most placental abnormalities, other than higher odds for inflammatory abnormalities in Q2 compared to Q1 [adjOR(95%CI): 1.50(1.00, 2.24)]. PW was also higher in Q2-4 compared to Q1 [adjβ(95%CI): 123.96(56.74, 191.19); 59.89(12.83, 106.94); 106.83(38.73, 174.94)]. Steeper β-HCG rise was associated with more vascular placental abnormalities, only following fresh SET.Overall, PW was found to be lower in the lowest quartile of %HCG rise, both before and after stratification to fresh and frozen SET.