< 37 ≥ 37 ≥ 25 Race White Asian Black/African American Hispanic/other Smoking Never smoker Ever smoker Current smoker Former smoker SART diagnosisb Female factor infertility Diminished ovarian reserve Ovulation disorders Endometriosis Uterine disorders Tubal factor Male factor infertility Unexplained Otherc Low-dose leuprolide lupron Regular-dose leuprolide lupron 137 women [n (%)]. Characteristic IVF protocol Luteal phase Day 3 FSH (IU/L) Peak E2 (pg/mL)a Flare Antagonist Mean ± SD Range Mean ± SD Range Thin (≤ 8 mm) Mean ± SD Range Endometrial thicknessa Day of embryo transfer No. of embryos transferred 3 5 1 2 ≥ 3 980 79 (58) 58 (42) 45 (33) 119 (87) 5 (4) 8 (6) 5 (4) 98 (72) 39 (28) 5 (4) 34 (25) 49 (36) 13 (26) 14 (29) 11 (22) 1 (2) 10 (20) 49 (36) 36 (26) 3 (2) IVF cyles 109 (61) 102 (57) 7 (4) 47 (26) 24 (13) 7.3 ± 2.3 1.0–15.2 2,051 ± 819 551–4,455 35 (19) 10.3 ± 2.0 6–19 120 (67) 60 (33) 24 (13) 109 (61) 47 (26) 17 (40) 26 (60) 18 (42) 35 (81) 2 (5) 2 (5) 4 (9) 32 (74) 11 (26) 2 (5) 9 (21) 20 (46) 7 (35) 2 (10) 6 (30) 0 (0) 5 (25) 13 (30) 7 (16) 3 (7) 33 (44) 31 (41) 2 (3) 27 (36) 15 (20) 7.6 ± 2.3 1–15.2 2,040 ± 874 551–4,126 16 (21) 10.1 ± 1.9 7–15 57 (76) 18 (24) 11 (15) 39 (52) 25 (33) Ehrlich et al. type (flare/antagonist vs. regular luteal phase protocol); day­3 serum FSH level (inter­ national units per liter, a measure of ovarian reserve); peak serum E2 (this corresponded to the last serum E2 measurement, 2 days before egg retrieval); endometrium thickness (< 9 mm vs. ≥ 9 mm); smoking (ever vs. never smoker); and body mass index (BMI) [overweight/obese (BMI ≥ 25 kg/m2) vs. normal/underweight (BMI < 25 kg/m2)]. Covariates that predicted implantation failure with p < 0.2 in univariate models and present in ≥ 5% of the cohort were evaluated for inclusion in the multi­ variate model using backward selection, and they were retained in the final model if their p was ≥ 0.10 or if the effect estimate changed Table 1. Subject demographics and infertility diagnoses among 137 women undergoing IVF [n (%)]. Characteristic Total (n = 137) Age [years; mean ± SD (range)] 35.8 ± 4.0 (21 – 44) 37.0 ± 4.8 (21 – 44) 35.2 ± 3.5 (28 – 43) Implantation failure since entry to study Ever had (n = 43) Never had (n = 94) BMIa [kg/m2; mean ± SD (range)] 24.7 ± 5.0 (16.5 – 42) 26.2 ± 5.5 (17.5 – 42.3) 23.9 ± 4.6 (16.5 – 39.1) Due to rounding, percentage totals may not sum to 100%. aBMI missing for 1 subject from implantation group. bPrimary diagnosis of infertility. cOther SART diagnoses: balanced translocation, Canavan’s disease, irregular antibodies. Table 2. Treatment protocols, cycle characteristics, and pregnancy outcomes for 180 IVF cycles among Implantation failure (n = 75) Implantation (n = 105) 62 (66) 32 (34) 27 (29) 84 (89) 3 (3) 6 (6) 1 (1) 66 (70) 28 (30) 3 (3) 25 (27) 29 (31) 6 (21) 12 (41) 5 (17) 1 (3) 5 (17) 36 (38) 29 (31) 0 (0) 76 (72) 71 (68) 5 (5) 20 (19) 9 (9) 7.1 ± 2.3 1–15.2 2,060 ± 783 635–4,455 19 (18) 10.4 ± 2.1 6–19 63 (60) 42 (40) 13 (12) 70 (67) 22 (21) by > 10% when the covariates were removed. A test for trend was performed to determine if there was a linear dose–response relationship between quartiles of urinary BPA and implan­ tation failure. The trend test was performed by modeling the BPA quartiles as an ordinal categorical variable, using the integer values 0, 1, 2, and 3 for BPA quartiles 1, 2, 3, and 4, respectively. As an alternative to the GEE model approach based on a logistic link, log bino­ mial models for the relative risk were also fit. Because these models did not always con­ verge, but yielded similar results when they did, they are not presented here. In addition, analyses restricted to first cycles only were also performed. Because the choice of IVF treatment pro­ tocol used in a given cycle is determined by the patient’s anticipated probability of suc­ cess based in part on past implantation failures and because past urinary BPA concentrations may be associated with past implantation fail­ ures and correlated with current BPA con­ centrations, we considered protocol type as a potential intermediate on the causal path­ way between urinary BPA concentration and implantation failure. We therefore present model results both adjusted and unadjusted for treatment protocol. We also conducted a strati­ fied analysis by type of treatment protocol. All data analyses were performed using SAS version 9.2 (SAS Institute Inc., Cary, NC). Results The 137 women included in this analysis were on average 35.8 years of age, 87% were Caucasian, and < 5% were current smokers (Table 1). Approximately one­third of the couples had a primary SART diagnosis of female infertility, a third had male factor infertility, and a third had unexplained infer­ tility. Women who had ever had a treatment cycle that resulted in an implantation failure were on average 2 years older than those who had never experienced an implantation failure. The primary treatment protocol for the 180 IVF cycles undergone by the 137 study par­ ticipants was the luteal phase GnRH agonist protocol (61% of cycles; Table 2). Only 13% of the embryo transfers were single embryo transfers, and one third of the transfers were on day 5 at the blastocyst stage. The 325 urine samples provided by the 137 women had urinary BPA concentrations that were comparable to general population concentrations from NHANES participants. The geometric mean was 1.53 µg/L compared with 1.97 µg/L for females in NHANES 2007–2008 (CDC 2011) (Table 3). Two urine samples were collected in 80% (144/180) of cycles. No significant differences (at p < 0.05) in baseline characteristics were noted between women who contributed one Due to rounding, percentage totals may not equal 100%. aMissing 10 peak E2 and endometrial thicknesses; the mean number of cycles was 1.3 cycles/woman. ovlume 120 | number 7 | July 2012 • Environmental Health Perspectives