Urinary Concentrations of Phthalate Metabolites and Pregnancy Loss Among Women Conceiving with Medically Assisted Reproduction.
Animal studies demonstrate that several phthalates are embryofetotoxic and are associated with increased pregnancy loss and malformations. Results from human studies on phthalates and pregnancy loss are inconsistent.



We examined pregnancy loss prospectively in relation to urinary phthalate metabolite concentrations among women undergoing medically assisted reproduction. We used data from 256 women conceiving 303 pregnancies recruited between 2004 and 2012 from the Massachusetts General Hospital Fertility Center. We quantified 11 phthalate metabolite concentrations and calculated the molar sum of four di(2-ethylhexyl) phthalate (DEHP) metabolites (ΣDEHP). We estimated risk ratios (RRs) and 95% confidence intervals for biochemical loss and total pregnancy loss (<20 weeks' gestation) across quartiles using repeated measures log-binomial models, adjusted for age, body mass index, smoking and infertility diagnosis.



Of the 303 pregnancies, 83 (27%) ended in loss less than 20 weeks' gestation and among these, 31 (10%) ended in biochemical loss. Although imprecise, the RRs for biochemical loss increased across quartiles of ΣDEHP and three individual DEHP metabolites. For ΣDEHP, the RRs (confidence intervals) were 2.3 (0.63, 8.5), 2.0 (0.58, 7.2), and 3.4 (0.97, 11.7) for quartiles two, three, and four, compared with one, respectively (P trend = 0.04). RRs for total pregnancy loss were elevated in the highest quartiles of ΣDEHP and three DEHP metabolites. The remaining seven phthalate metabolite concentrations evaluated were not associated with either outcome.



We found a suggestive pattern of association between conception cycle-specific urinary concentrations of DEHP metabolites and biochemical and total pregnancy loss among women undergoing medically assisted reproduction.
From the aDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA; bDivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; cDepartment of Biostatistics, dDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; eMassachusetts General Hospital Fertility Center, Department of Obstetrics and Gynecology, Harvard Medical School, Boston, MA; fNational Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA; and gVincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Carmen
C
Messerlian
Blair J
BJ
Wylie
Lidia
L
Mínguez-Alarcón
Paige L
PL
Williams
Jennifer B
JB
Ford
Irene C
IC
Souter
Antonia M
AM
Calafat
Russ
R
Hauser
D000022:Abortion, Spontaneous / Q000139:chemically induced* / Q000652:urine; D000293:Adolescent; D000328:Adult; D004051:Diethylhexyl Phthalate / Q000633:toxicity* / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D004785:Environmental Pollutants / Q000633:toxicity* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008404:Massachusetts; D008875:Middle Aged; D015233:Models, Statistical; D011247:Pregnancy; D011446:Prospective Studies; D027724:Reproductive Techniques, Assisted; D055815:Young Adult
D004785:Environmental Pollutants; D004051:Diethylhexyl Phthalate