Environmental Influences on Female Fecundity and Fertility

 

 Buy Article Permissions and Reprints

ABSTRACT

An increasing body of evidence suggests that environmental exposures are adversely influencing female fecundity and fertility. Endocrine-disrupting compounds (EDCs) are of particular concern, due to their ability to interfere with the body's hormonal milieu. An overview of the literature regarding the effect of EDCs on female fecundity and fertility end points such as puberty, menstruation, endometriosis, time to pregnancy, pregnancy loss, reproductive senescence, and secondary sex ratio is presented. Methodologic challenges in studying the effects EDCs on sensitive reproductive end points are discussed and include exposure to mixtures, the choice of biologic media in which to measure compounds, laboratory methods, and varying modeling techniques. Also reviewed are novel technologies for home-based biospecimen collection and testing that offer promise for field-based research aimed at addressing questions about environmental influences on female fecundity and fertility.

REFERENCES

• 1 Thomas K B, Colborn T. Organochlorine endocrine disruptors in human tissue. In: Colborn T, Clement C Chemically Induced Alterations in Sexual Development: The Wildlife/Human Connection. Princeton, NJ; Princeton Scientific 1992: 365-394
  Google Scholar
• 2 Colborn T, vom Saal F S, Soto A M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans.  Environ Health Perspect. 1993;  101 378-384
  PubMedGoogle Scholar
• 3 Orberg J, Kihlstrom J E. Effects of long-term feeding of polychlorinated biphenyls (PCB, Clophen A 60) on the length of the oestrous cycle and on the frequency of implanted ova in the mouse.  Environ Res. 1973;  6 176-179
  CrossrefPubMedGoogle Scholar
• 4 Brezner E, Terkel J, Perry A S. The effect of Aroclor 1254 (PCB) on the physiology of reproduction in the female rat-I.  Comp Biochem Physiol C. 1984;  77 65-70
  CrossrefPubMedGoogle Scholar
• 5 Muller W F, Hobson W, Fuller G B, Knauf W, Coulston F, Korte F. Endocrine effects of chlorinated hydrocarbons in rhesus monkeys.  Ecotoxicol Environ Saf. 1978;  2 161-172
  CrossrefPubMedGoogle Scholar
• 6 Gellert R J. Uterotrophic activity of polychlorinated biphenyls (PCB) and induction of precocious reproductive aging in neonatally treated female rats.  Environ Res. 1978;  16 123-130
  CrossrefPubMedGoogle Scholar
• 7 Aulerich R J, Bursian S J, Breslin W J, Olson B A, Ringer R K. Toxicological manifestations of 2,4,5,2′,4′,5′-, 2,3,6,2′,3′,6′-, and 3,4,5,3′,4′,5′-hexachlorobiphenyl and Aroclor 1254 in mink.  J Toxicol Environ Health. 1985;  15 63-79
  PubMedGoogle Scholar
• 8 Crisp T M, Clegg E D, Cooper R L et al.. Environmental endocrine disruption: an effects assessment and analysis.  Environ Health Perspect. 1998;  106(suppl 1) 11-56
  PubMedGoogle Scholar
• 9 National Research Council .Hormonally Active Agents in the Environment. Washington, DC; National Academy Press 2000
  Google Scholar
• 10 Brouwer A, Morse D C, Lans M C et al.. Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health.  Toxicol Ind Health. 1998;  14 59-84
  PubMedGoogle Scholar
• 11 Butler D. The fertility riddle.  Nature. 2004;  432 38-39
  PubMedGoogle Scholar
• 12 Wood J M. Dynamics of Human Reproduction: Biology, Biometry, Demography. New York; Aldine de Gruyter 1994: 3-22
  Google Scholar
• 13 Wilcox A J, Dunson D, Baird D D. The timing of the “fertile window” in the menstrual cycle: day specific estimates from a prospective study.  BMJ. 2000;  321 1259-1262
  CrossrefPubMedGoogle Scholar
• 14 Joffe M. Infertility and environmental pollutants.  Br Med Bull. 2003;  68 47-70
  PubMedGoogle Scholar
• 15 Wilson J G. Embryological considerations in teratology. In: Teratology: Principles and Techniques. Wilson JG, Warkany J Chicago; The University of Chicago Press 1965
• 16 Chapin R E, Robbins W A, Schieve L A, Sweeney A M, Tabacova S A, Tomashek K M. Off to a good start: the influence of pre- and periconceptional exposures, parental fertility, and nutrition on children's health.  Environ Health Perspect. 2004;  112 69-78
  PubMedGoogle Scholar
• 17 Selevan S G, Kimmel C A, Mendola P. Identifying critical windows of exposure for children's health.  Environ Health Perspect. 2000;  108(suppl 3) 451-455
  PubMedGoogle Scholar
• 18 Morford L L, Henck J W, Breslin W J, DeSesso J M. Hazard identification and predictability of children's health risk from animal data.  Environ Health Perspect. 2004;  112 266-271
  PubMedGoogle Scholar
• 19 Dunson D B, Baird D D, Wilcox A J, Weinberg C R. Day-specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation.  Hum Reprod. 1999;  14 1835-1839
  CrossrefPubMedGoogle Scholar
• 20 DeRosa C, Richter P, Pohl H, Jones D E. Environmental exposures that affect the endocrine system: public health implications.  J Toxicol Environ Health B Crit Rev. 1998;  1 3-26
  PubMedGoogle Scholar
• 21 Sonnenschein C, Soto A M. An updated review of environmental estrogen and androgen mimics and antagonists.  J Steroid Biochem Mol Biol. 1998;  65 143-150
  CrossrefPubMedGoogle Scholar
• 22 Cooke P S, Sato T, Buchanan D L. Disruption of steroid hormone signaling by PCBs. In: PCBs: Recent Advances in Environmental Toxicology and Health Effects. Robertson LW, Hansen LG Lexington, KY; The University Press of Kentucky 2001: 257-263
  Google Scholar
• 23 James M O. Polychlorinated biphenyls: metabolism and metabolites. In: PCBs: Recent Advances in Environmental Toxicology and Health Effects. Robertson LW, Hansen LG Lexington, KY; The University Press of Kentucky 2001: 35-46
  Google Scholar
• 24 Younglai E V, Foster W G, Hughes E G, Trim K, Jarrell J F. Levels of environmental contaminants in human follicular fluid, serum, and seminal plasma of couples undergoing in vitro fertilization.  Arch Environ Contam Toxicol. 2002;  43 121-126
  CrossrefPubMedGoogle Scholar
• 25 Schisterman E F, Vexler A, Whitcomb B W, Liu A. The limitations due to exposure detection limits for regression models.  Am J Epidemiol. 2005;  163 374-383
  CrossrefPubMedGoogle Scholar
• 26 Schisterman E F, Whitcomb B W, Louis G M, Louis T A. Lipid adjustment in the analysis of environmental contaminants and human health risks.  Environ Health Perspect. 2005;  113 853-857
  PubMedGoogle Scholar
• 27 Rockett J C, Buck G M, Lynch C D, Perreault S D. The value of home-based collection of biospecimens in reproductive epidemiology.  Environ Health Perspect. 2004;  112 94-104
  PubMedGoogle Scholar
• 28 World Health Organization, Task Force on Methods for the Determination of the Fertile Period . Temporal relationships between ovulation and defined changes in the concentration of plasma estradiol-17 beta, luteinizing hormone, follicle-stimulating hormone, and progesterone. I. Probit analysis.  Am J Obstet Gynecol. 1980;  138 383-390
  PubMedGoogle Scholar
• 29 Leavitt S A. A thin blue line: the history of the pregnancy test kit. Bethesda, MD; Office of NIH HIstory, DHH5 2003 Available at: http://www.history.nih.gov/exhibits/thin blueline/index.html Accessed May 19, 2006
  Google Scholar
• 30 Ehrenkranz J R. Home and point-of-care pregnancy tests: a review of the technology.  Epidemiology. 2002;  13 S15-S18
  CrossrefPubMedGoogle Scholar
• 31 Buck G M, Lynch C D, Stanford J B et al.. Prospective pregnancy study designs for assessing reproductive and developmental toxicants.  Environ Health Perspect. 2004;  112 79-86
  PubMedGoogle Scholar
• 32 Blanck H M, Marcus M, Tolbert P E et al.. Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl.  Epidemiology. 2000;  11 641-647
  PubMedGoogle Scholar
• 33 Krstevska-Konstantinova M, Charlier C, Craen M et al.. Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticides.  Hum Reprod. 2001;  16 1020-1026
  CrossrefPubMedGoogle Scholar
• 34 Wu T, Buck G M, Mendola P. Blood lead levels and sexual maturation in U.S. girls: the Third National Health and Nutrition Examination Survey, 1988-1994.  Environ Health Perspect. 2003;  111 737-741
  PubMedGoogle Scholar
• 35 Warner M, Samuels S, Mocarelli P et al.. Serum dioxin concentrations and age at menarche.  Environ Health Perspect. 2004;  112 1289-1292
  PubMedGoogle Scholar
• 36 Denham M, Schell L M, Deane G, Gallo M V, Ravenscroft J, DeCaprio A P. Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls.  Pediatrics. 2005;  115 e127-e134
  CrossrefPubMedGoogle Scholar
• 37 Mendola P, Buck G M, Sever L E, Zielezny M, Vena J E. Consumption of PCB-contaminated freshwater fish and shortened menstrual cycle length.  Am J Epidemiol. 1997;  146 955-960
  PubMedGoogle Scholar
• 38 Yu M L, Guo Y L, Hsu C C, Rogan W J. Menstruation and reproduction in women with polychlorinated biphenyl (PCB) poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng cohort.  Int J Epidemiol. 2000;  29 672-677
  CrossrefPubMedGoogle Scholar
• 39 Eskenazi B, Warner M, Mocarelli P et al.. Serum dioxin concentrations and menstrual cycle characteristics.  Am J Epidemiol. 2002;  156 383-392
  CrossrefPubMedGoogle Scholar
• 40 Cooper G S, Klebanoff M A, Promislow J, Brock J W, Longnecker M P. Polychlorinated biphenyls and menstrual cycle characteristics.  Epidemiology. 2005;  16 191-200
  CrossrefPubMedGoogle Scholar
• 41 Windham G C, Lee D, Mitchell P, Anderson M, Petreas M, Lasley B. Exposure to organochlorine compounds and effects on ovarian function.  Epidemiology. 2005;  16 182-190
  CrossrefPubMedGoogle Scholar
• 42 Gerhard I, Runnebaum B. The limits of hormone substitution in pollutant exposure and fertility disorders.  Zentralbl Gynakol. 1992;  114 593-602
  PubMedGoogle Scholar
• 43 Mayani A, Barel S, Soback S, Almagor M. Dioxin concentrations in women with endometriosis.  Hum Reprod. 1997;  12 373-375
  CrossrefPubMedGoogle Scholar
• 44 Lebel G, Dodin S, Ayotte P, Marcoux S, Ferron L A, Dewailly E. Organochlorine exposure and the risk of endometriosis.  Fertil Steril. 1998;  69 221-228
  CrossrefPubMedGoogle Scholar
• 45 Pauwels A, Schepens P J, D'Hooghe T et al.. The risk of endometriosis and exposure to dioxins and polychlorinated biphenyls: a case-control study of infertile women.  Hum Reprod. 2001;  16 2050-2055
  CrossrefPubMedGoogle Scholar
• 46 Louis G M, Weiner J M, Whitcomb B W et al.. Environmental PCB exposure and risk of endometriosis.  Hum Reprod. 2005;  20 279-285
  PubMedGoogle Scholar
• 47 Rachootin P, Olsen J. The risk of infertility and delayed conception associated with exposures in the Danish workplace.  J Occup Med. 1983;  25 394-402
  PubMedGoogle Scholar
• 48 Curtis K M, Savitz D A, Weinberg C R, Arbuckle T E. The effect of pesticide exposure on time to pregnancy.  Epidemiology. 1999;  10 112-117
  PubMedGoogle Scholar
• 49 Thonneau P, Abell A, Larsen S B et al.. Effects of pesticide exposure on time to pregnancy: results of a multicenter study in France and Denmark. ASCLEPIOS Study Group.  Am J Epidemiol. 1999;  150 157-163
  PubMedGoogle Scholar
• 50 Axmon A, Rylander L, Stromberg U, Hagmar L. Time to pregnancy and infertility among women with a high intake of fish contaminated with persistent organochlorine compounds.  Scand J Work Environ Health. 2000;  26 199-206
  PubMedGoogle Scholar
• 51 Buck G M, Vena J E, Schisterman E F et al.. Parental consumption of contaminated sport fish from Lake Ontario and predicted fecundability.  Epidemiology. 2000;  11 388-393
  CrossrefPubMedGoogle Scholar
• 52 Axmon A, Rylander L, Stromberg U, Jonsson B, Nilsson-Ehle P, Hagmar L. Polychlorinated biphenyls in serum and time to pregnancy.  Environ Res. 2004;  96 186-195
  CrossrefPubMedGoogle Scholar
• 53 Law D C, Klebanoff M A, Brock J W, Dunson D B, Longnecker M P. Maternal serum levels of polychlorinated biphenyls and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and time to pregnancy.  Am J Epidemiol. 2005;  162 523-532
  CrossrefPubMedGoogle Scholar
• 54 Saxena M C, Siddiqui M K, Seth T D, Krishna Murti C R, Bhargava A K, Kutty D. Organochlorine pesticides in specimens from women undergoing spontaneous abortion, premature of full-term delivery.  J Anal Toxicol. 1981;  5 6-9
  PubMedGoogle Scholar
• 55 Leoni V, Fabiani L, Marinelli G et al.. PCB and other organochlorine compounds in blood of women with or without miscarriage: a hypothesis of correlation.  Ecotoxicol Environ Saf. 1989;  17 1-11
  CrossrefPubMedGoogle Scholar
• 56 Dar E, Kanarek M S, Anderson H A, Sonzogni W C. Fish consumption and reproductive outcomes in Green Bay, Wisconsin.  Environ Res. 1992;  59 189-201
  CrossrefPubMedGoogle Scholar
• 57 Mendola P, Buck G M, Vena J E, Zielezny M, Sever L E. Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death.  Environ Health Perspect. 1995;  103 498-502
  PubMedGoogle Scholar
• 58 Gerhard I, Daniel V, Link S, Monga B, Runnebaum B. Chlorinated hydrocarbons in women with repeated miscarriages.  Environ Health Perspect. 1998;  106 675-681
  PubMedGoogle Scholar
• 59 Korrick S A, Chen C, Damokosh A I et al.. Association of DDT with spontaneous abortion: a case-control study.  Ann Epidemiol. 2001;  11 491-496
  CrossrefPubMedGoogle Scholar
• 60 Axmon A, Rylander L, Stromberg U, Hagmar L. Female fertility in relation to the consumption of fish contaminated with persistent organochlorine compounds.  Scand J Work Environ Health. 2002;  28 124-132
  PubMedGoogle Scholar
• 61 Sugiura-Ogasawara M, Ozaki Y, Sonta S, Makino T, Suzumori K. PCBs, hexachlorobenzene and DDE are not associated with recurrent miscarriage.  Am J Reprod Immunol. 2003;  50 485-489
  CrossrefPubMedGoogle Scholar
• 62 Longnecker M P, Klebanoff M A, Dunson D B et al.. Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies.  Environ Res. 2005;  97 127-133
  CrossrefPubMedGoogle Scholar
• 63 Venners S A, Korrick S, Xu X et al.. Preconception serum DDT and pregnancy loss: a prospective study using a biomarker of pregnancy.  Am J Epidemiol. 2005;  162 709-716
  CrossrefPubMedGoogle Scholar
• 64 Cooper G S, Savitz D A, Millikan R, Chiu K T. Organochlorine exposure and age at natural menopause.  Epidemiology. 2002;  13 729-733
  CrossrefPubMedGoogle Scholar
• 65 Blanck H M, Marcus M, Tolbert P E et al.. Time to menopause in relation to PBBs, PCBs, and smoking.  Maturitas. 2004;  49 97-106
  CrossrefPubMedGoogle Scholar
• 66 Rylander L, Stromberg U, Hagmar L. Decreased birthweight among infants born to women with a high dietary intake of fish contaminated with persistent organochlorine compounds.  Scand J Work Environ Health. 1995;  21 368-375
  PubMedGoogle Scholar
• 67 James W H. Fish eaters and sex ratio.  J Occup Environ Med. 2002;  44 885-886
  PubMedGoogle Scholar
• 68 Weisskopf M G, Anderson H A, Hanrahan L P. Decreased sex ratio following maternal exposure to polychlorinated biphenyls from contaminated Great Lakes sport-caught fish: a retrospective cohort study.  Environ Health. 2003;  2 2
  CrossrefPubMedGoogle Scholar

 Dr.
Germaine M Buck Louis

Epidemiology Branch, Division of Epidemiology, Statistics & Prevention Research, National Institute of Child Health & Human Development

6100 Executive Blvd., Room 7B03, Rockville, MD 20852

Email: louisg@mail.nih.gov