Environmental Toxicants and Fertility / Pregnancy Compromise
09:00 am US Eastern Time
Moderator: Michael Lerner, President, Commonweal
1. First Speaker: Ted Schettler, M.D., M.P.H., Science Director, Science and Environmental Health Network
For more details on this topic, please see the summary paper, Infertility and Related Reproductive Disorders.
Most people consider infertility to be the failure to conceive a child after twelve months of unprotected intercourse. About 10-15% of couples meet this definition. One problem has been monitoring fertility trends. For several reasons:
1) Some couples have purposely delayed childbearing until later years and fertility problems increase with age. But this is not the entire story, since even within specific age groups, impaired fertility is increasing.
2) Increased reporting of fertility problems may also result because of the availability of assisted reproduction technologies.
3) Access to medical care can also influence reporting.
Decreased fertility does not necessarily mean lack of conception. A fertilized egg may not implant normally or the embryo may not survive after implantation and early miscarriages may actually be interpreted as a fertility problem. In the general population about 50% of fertilized eggs do not progress to a viable pregnancy and about 30% of pregnancies are lost in the first 6 weeks.
Fertility problems can be attributed to male factors, female factors and couple dependant factors. They roughly break down to about 30% each among those. For the male factor the issue that's received the most attention is sperm counts and sperm quality. Most recent analysis suggests a decline in sperm count in at least some geographical areas. These do suggest that environmental factors play a role in agricultural, chemical, some chemicals commonly encountered in consumer products and endocrine disrupting chemicals are leading candidates. With respect to female factors, the failure to ovulate normally can be caused by genetic or environmental factors, premature menopause, abnormalities of the reproductive tract, and hormone imbalances may all contribute. Among couple dependant factors are incompatibility between sperm and cervical mucous or sperm antibodies may be responsible for infertility.
The above mentioned paper, includes references to scientific studies that have pointed to various solvents, pesticides, gases, metals, cigarette smoke and other air pollutants as contributing to infertility, in some cases through male mediated factors and in other cases, female. Some of these have been known for a long time, for example, some male agricultural workers who have been permanently sterilized by exposure to specific pesticides like DBCP, or glycol-ethers in people who work in solvent-exposed industries.
Finally there are concerns rising about the impacts of early life exposures and subsequent fertility. The Diethylstilbestrol (DES) case is instructive, showing us that in-utero exposures can result in health impacts that are only realized years or decades later. In the case of DES, abnormalities of the reproductive tract, immune system abnormalities and of course increased risk of certain kinds of reproductive tract malignancies.
The emergence of the impacts on the male reproductive tract, which go beyond sperm counts and include birth defects like hypospadias, undescended testies, and subsequent testicular cancer, along with decline in sperm counts and quality have led to the notion of Testicular Dysgenesis Syndrome. An idea that fetal exposures to endocrine disrupting chemicals like estrogenic or anti-Androgenic chemicals may have a constellation of effects and sperm quality and fertility are only one manifestation of that.
In Health Care Without Harm, we've also been particularly concerned with exposure to Phathalates, which come from medical devices, in particular DEHP, which is used for certain medical treatments where the animal data suggests that fetal or neo-natal exposure can impair normal development of the male reproductive tract and then subsequent fertility. Although this has never been studied in humans the concern is that early life exposures, in the fetus or neonate, may result in impaired fertility later in life. One of the challenges in linking fetal or neonatal exposures to subsequent fertility problems, years later is this long, intervening latent period. This kind of epidemiological investigation is difficult to do and the technical challenges may delay our understanding for quite some time.
2. Second Speaker: Shanna Swan, Research Professor, University of Missouri, Columbia, Family and Community Medicine
We've been conducting Study's for Future Families, in which we enroll couples through prenatal clinics in several cities. These are just couples seeking routine prenatal care, excluding those whose conceptions were medically assisted. We published a paper last year showing that semen quality was significantly poorer in men from mid-Missouri than in men from our urban centers. We compared mid-Missouri to these centers and after ruling out possible explanations such as demographics or the way the sperm was analyzed, we speculated that agricultural exposures may be responsible for these differences.
The second study examined this hypothesis. Here our main finding was that men who had elevated levels of urinary metabolites of three currently used pesticides alachlor, atrazine and diazanon, were significantly more likely to belong to the group of men with decreased semen quality than the men with lower levels of these pesticides.
The risk of poor semen quality was elevated about 30 fold among men with high alachlor levels. That is in the top third of alachlor levels not necessarily very high. The risk was increased 17 fold in men who had the higher levels of the diazanon metabolite, and 11 fold higher in men with detectable atrazine levels. Although these are based on small numbers, the associations are very strong and highly statistically significant. Because of the short half-life of these pesticides in the human body, we know that this study reflects current and not prenatal exposure. And also because there were a few farmers in this study, we know that this reflects environmental and not occupational exposures.
No other studies have linked these pesticides to men's semen quality. Before ours, only one study of semen quality was conducted in an agricultural area comparable to mid-Missouri. This is because to do a semen study, you need a lab, which is usually in urban centers. The other study that had been done in Iowa City in 1974 also showed low semen quality. Atrazine and alacholr had been used at that time, but the sensitive assays that we needed for our studies were not available, so they could not look at this hypothesis.
How does this study differ from other studies on semen quality?
1) Our study is the first to find that exposure to herbicides and pesticides currently in widespread use in the Midwest and elsewhere, may decrease semen quality.
2) Our study is the first to link semen quality to a sample of the general population. This is not a study of farmers, or men working in pesticides. This is not an infertility population. This is a population-based study.
3) This is the first study to measure biological levels of current use pesticides in a man's urine to see if these are linked to his semen quality.
More specifically, we drew from our Study for Future Families population men with poor semen quality and controls, who were living in mid-Missouri or Minneapolis, the 2 groups we wanted to contrast. All of these men provided a urine sample on the day of their semen sample. First we compared levels of 15 pesticide metabolites from cases in controls. But exposure was very different in Missouri and Minnesota. In Minneapolis, men had very little exposure to pesticides and these levels were quite high in men from mid-Missouri. Therefore, we conducted a separate analysis in each center. We measured semen concentration, the number of sperm contained in one milliliter, motility and morphology. Because we used the same standard methods at each center and strict quality control, we are quite confident that our results are not reflecting differences in methods of subject recruitment or semen analysis. We measured pesticides in the urine, through the Centers for Disease Control, using a highly sensitive pesticide screen. They did this blinded to the men's semen quality and the city in which they lived.
Now, how are people being exposed if it's not occupational? Recent USGS reports demonstrate that the pesticides we found associated with semen are often found in drinking water sources. They stated that water treatment methods do not remove these pesticides. We believe that drinking water is an important source of exposure. Other possible routes are air, food, or skin, and that's something we have to study.
So now, we're examining semen quality in men in Iowa City. It's looking like those men will also have very low semen quality. We're sending their samples to CDC, but we don't have those results yet. We also need to do toxicity tests to see if the women and children in those families are also affected.
3. Third Speaker: Rita Loch-Caruso, Professor of Toxicology, Department of Environmental Health Sciences, University of Michigan School of Public Health
In our lab, we're primarily interested in addressing the question of whether complications with childbirth are related to exposures to environmental toxicants. I had been looking at statistics of pre-term birth (birth prior to 37 weeks of gestation), which have been rising despite advances in pre-natal care. Pre-term birth stands at 11.9% of infants born. This is an increase of more than 27% from 1981. We have not been able to stem that rise, and prematurity is the second leading cause of infant death in the U.S. and the leading cause of death for African American infants.
Childbirth or parturition requires 2 basic events: cervical ripening and the coordination of contractions of the uterus with increased force. The uterus is usually studied as a biosensor organ for toxicants. So they're looking for an estrogenic response, an increased uterine weight. What is often overlooked is that the uterus is primarily a muscle and it has a very specific function during pregnancy, which is to remain quiescent or inactive throughout most of the pregnancy and as term approaches, to convert to a highly active state. Most pre-term births have been associated with an increase in uterine activity.
We've been focusing on the effects of toxicants on uterine contractions. But there is a flip side to pre-term birth, which is an interference with the normal parturition process and cesarean sections are also on the rise in the U.S. with non-progressive, long labor being the major cause of primary cesarean delivery. The non-progression of labor has been associated with increased maternal age and with first births. What also increases with maternal age and first births is a higher maternal body burden. With each subsequent pregnancy, the body burden reduces, due to mobilization of fats, especially if she nurses her babies.
We've been looking for biological plausibility that could link environmental exposures with complications of parturition. We've been taking in-vitro approaches using rodent uterine cells and looking for direct effects of toxicants on the uterine muscle. We've shown that PCBs in mixtures as well as PCBs individually have a direct impact on uterine contractility. They can stall or inhibit the uterus. Other conjoiners or mixtures can be very stimulatory. We've seen the greatest stimulation with PCBs, greater than oxytocin. We've also shown that treatment of uterine tissue with an estrogenic PCB enhances the tissues ability to respond to oxytocin, a hormone which is a part of the normal process of parturition. This suggests that there can be an indirect hormone mechanism by which toxicants may modify parturition. In this case estrogens are known to increase the expression of oxytocin receptors.
We've looked at a wide range of PCB conjoiners, several PCB mixtures, lindane and DDT isomeres. We've shown that there are effects on the uterine muscle that are consistent with some of the effects that have been observed with epidemiology studies. Our main interest has been to provide biological plausibility for associations that have been observed.
4. Fourth Speaker: Edith Eddy, Executive Director, Compton Foundation
Coincidentally I am calling from the Funders Network on Population, Reproductive Health and Rights annual meeting. Six years ago when this group first started only 6 people came, this morning we had 25. The increase of interest in this field is welcome.
The issues that motivate population groups to be interested are a focus on patient services, justice and rights issues, socio-economic status issues, and environmental justice. There are also very strong issues that prevent organizations in the reproductive rights and reproductive health field from embracing these issues.
1) This field is currently under siege from the policies of the current administration and congress. There are many competing issues that are demanding money when the availability of resources has gone down. So, there is prioritization and infertility is a new field for reproductive health advocates. They've got an already full plate.
2) There is a historical problem of focusing on the health of the fetus. The right to life community has put its attention on the health of the fetus. The reproductive rights community has focused on the woman's health and ability to determine her own life. So shifting to a focus on the fetus, is both scary, and unfamiliar, but it also holds great promise. This morning we focused on the fetus, how to re-claim the fetus, what kind of language to use.
3) The reproductive rights and reproductive health community is more focused on advocacy and service, and not research oriented. The state of research in this field is still very much in a developmental phase. We're learning things that point in certain directions, but we're not yet able to claim certainty about very much. There is a great need for increased and easily distilled information.
There is a growing interest. People want to learn more and be better informed. There are organizations including the Planned Parenthood Federation of America that is beginning to think about how it might embrace this issue and offer infertility services.
We also need to reach out and include men, as they have all but disappeared from that. There is a promising recognition that infertility affects men just as much as women. Looking at this as a couple's issue, rather than just an individual's issue holds great promise.
5. Question and Answer/Concluding Remarks
Tina Eshaghpour: We've been attempting to bring together the science with the anecdotal stories that we've heard from organizations that we fund around California, on the issue of environmental health. We want to strengthen the links between reproductive rights and health and the environmental health communities. One of the key challenges that we face is in being able to respond to the fact that the science is still in a very developmental phase. Another challenge is how to begin to identify allies and communities that may not historically have felt a connection, to understand how their constituents are affected, and to begin to help bridge those alliances with legislative issues, to start to enact policies that can help diminish or mitigate some of the effects of environmental exposures. How can we really start to build on this current momentum?
Maris Meyerson: RESOLVE is interested in environment and sperm, and particularly in inclusiveness and bringing men more into the fold. Connecting with men is one of the biggest concerns that RESOLVE has had.
Cynthia Pearson: The National Women's Health Network bridges both ways of looking at this issue as we have worked on infertility issues, cancer issues, and environmental issues. What we've been confronted with is the insistence that policy makers try to make on having a scientific answer before a policy reaction is formulated. So having the research be so much further along and really much closer to conclusive, or being able to pinpoint a specific chemical that's really affecting men's and women's reproductive health. Would other participants on the call like to share ideas about how to overcome that barrier?
Michael Lerner: This is absolutely on our agenda, and towards the end of this call, we will open up this conversation with Alison Carlson, who is interested in facilitating this dialogue.
Louise Mitchell: The Westin A. Price Foundation has studied indigenous cultures and their diets and practices as they prepared men and women for conception and pregnancy. The research focuses on optimal nutrition and protection against toxicants.
Michael Lerner: Edith, can you say something about funder interest in these issues and whether there's an emerging collaborative strategy of any kind among funders with respect to this?
Edith Eddy: There is no emerging strategy among funders. There is a higher level of interest in younger people than older people. A lot of the leadership is in older women. But it is among younger women and women of color, in the funding community, that you find the higher interest in this. I am optimistic that funding strategies may emerge, however I am guessing that there probably needs to be some organizing out in the world, particularly by health affected people who are really motivated to find what's going on.
Michael Lerner: Theo Colborn's book, Our Stolen Future, which really launched a great deal of this field, involved how these factors may be affecting our intelligence, health and fertility. You started as a wildlife researcher. Could you speak to the scope of the evidence that it's not just human fertility that's being compromised? To what degree is fertility and the rest of the community of life being compromised?
Theo Colborn: Some of the old studies on the effects that we found in wildlife and that we reported in our book have been replicated recently. The survival of the species and biodiversity is extremely threatened. But now we are learning that humans and the environment that they live in today is far more exposed to these new chemicals that we are just beginning to realize are out there that are also threatening our fertility. The wildlife biologists are now turning to the tools that we were trying to use for diagnosis and for determining the problems in wildlife. Humans are now being used as the model for what the wildlife biologists should be looking for. Most of the people don't realize that most of the food we eat today is artificially grown, and this is a very serious problem.
Linda Guidice: One potential way of unifying these constituencies may be to approach the IOM (Institute of Medicine) to set up a committee and a report. One advantage of working through the IOM, if one can get the funding, would be to de-politicize the whole issue. In addition it could bring together potential funders, foundations, interested parties, and the NIH. These kinds of committees have a multi-disciplinary representation. If this group thinks this would be an appropriate avenue to pursue I would be willing to bring it to the appropriate group.
Shanna Swan: I would definitely support that in any way I could.
Rita Loch-Caruso: I think it would be very productive. There was an IOM Conference on environmental chemicals in pre-term birth that brought attention to how little work has been done.
Theo Colburn: I think the greatest breakthrough would be through medicine and the medical profession. It would be terrific if you could do this.
Rich Liroff: This is an issue that works whether you're pro-life or you're pro-choice. Both sides care about the fetus.
Alison Carlson: It's been really inspiring to join these conversations. I am very enthusiastic and hopeful about collaborating via CHE with any and all of you who can contribute to enhancing this dialogue, building helpful bridges and moving toward a serious effort. I agree with Theo about the biggest breakthroughs coming from the medical community. One step out of the call could be the creation of a special interest work or advisory group, at first to define issues and challenges and goals. I would love to work with CHE to coordinate such a group. Anyone who is interested in furthering this dialogue can contact Alison at Contact or at 415-923-0817.
Michael Lerner: There were a number of new colleagues stressing the hope that we may identify ways of exploring this together. We do have a very robust example, in the Learning and Developmental Disabilities Initiative, of the kinds of constituencies that can come together to do this.
Elise Miller: Through LDDI we have almost 40 groups and individuals that are involved. Some of those groups include the Learning Disabilities Association, American Association of Mental Retardation, Communities Against Violence, Cure Autism Now, Autism Society of America. We also have a few key environmental groups that are working on neurotoxicants. This group comes together once a month to discuss the ways that we can both educate these constituencies and follow up on policy initiatives. This has become a great working model.
Elizabeth Sword: We are developing an outreach campaign to pregnant women and working to collaborate with ACOG (American College of Obstetrics and Gynecology) as an outreach mechanism. We're also reaching out to any kind of healthcare provider who would have contact with any woman who is pregnant or seeking to become pregnant, with the idea of getting information about environmental risks to the fetus as soon as possible. If anyone on this call can share recommendations, or would like to be part of that effort, we would welcome your input.
Tina Eshaghpour: As a result of the publication of our report we've gotten some interest from legislators around California. How in pulling together these allies we can really educate the public? Our report can be viewed at http://www.womensfoundca.org/publications.html.
Michael Lerner: We would like to encourage all of our new colleagues on this call to join CHE. As you know, CHE costs nothing to join, you receive no more than 2 emails a month and you're invited to participate on our monthly Partnership Calls. We have 700 Partners, organizations and individuals who care about the environment, how it's affecting our health and who are really committed to solid science and want to share information and opportunities for collaborative work and have the capacity to develop both within their organizations and collectively. Thank you all for joining us and we hope you'll join us again.