Abstract
Gerson Weiss speaks to Natasha Leeson, Assistant Commissioning Editor
Gerson Weiss obtained his MD degree from New York University (NY, USA). After an internship in internal medicine at Baltimore City Hospital (MD, USA), he completed residency in obstetrics and gynecology at New York University. Further training in reproductive endocrinology was obtained as a postdoctoral research fellow in physiology at the University of Pittsburgh (PA, USA), in the laboratory of Dr Ernst Knobil. Following this fellowship, Dr Weiss returned to New York University where he ultimately became Professor of Obstetrics and Gynecology, Professor of Pharmacology and Director of the Division of Reproductive Endocrinology and Infertility. In 1986, he became Professor and Chair of the Department of Obstetrics and Gynecology at New Jersey Medical School (NJ, USA). Dr Weiss is the author of more than 274 scientific articles. His research has been continuously funded since 1975 by grants from the NIH, the United Cerebral Palsy Foundation and the Andrew W Mellon Foundation. He has served as a member of the Division of Reproductive Endocrinology of the American Board of Obstetrics and Gynecology, a member of the Reproductive Biology Study Section of the NIH, a member of the Residency Review Committee for Obstetrics and Gynecology of the Accreditation Council for Graduate Medical Education. He has served as the President of the New York Obstetrical Society, the New York Gynecologic Society, the Council of University Chairs of Obstetrics and Gynecology, and the American Board of Obstetrics and Gynecology. He was the Chairman of the Committee on Gynecologic Practices for the American College of Obstetricians and Gynecologists and Chairman of American Board of Obstetrics and Gynecology. He was a member of the Executive Committee of the American Board of Medical Specialties. Dr Weiss is a past President of the Society for Gynecologic Investigation. He currently serves on the NIH's Advisory Committee on Research on Women's Health. Dr Weiss conducts an active clinical practice both in gynecology and reproductive endocrinology and infertility at his institution.
How did your career lead you to working in women's health?
In 1962, between my second and third year of medical school, I had a summer fellowship from New York City (NY, USA) on a cancer screening project with the Harlem Hospital (NY, USA). We were doing pap smears, and it was vividly clear that we were able to pick up precancer and eliminate it before it became malignant, which was very exciting. At that time, this was the only field where this could be done.
During my third year at medical school, I had some absolutely wonderful cases. Thus, it was clear to me that there were great outcomes in obstetrics and gynecology, and the results were immediate. These were interesting cases; I felt like I was actually doing something, making a difference.
Following my medical internship, residency and a stint in the Army, I took a research fellowship at the University of Pittsburgh (PA, USA). At that point, I was interested in how the menstrual cycle worked. I looked at the most recent publications in this field to see what was being done. Some were using rodent models, and I didn't see how the rodent was necessarily a good parallel to humans. However, one individual, Ernst Knobil, with whom I worked at the University of Pittsburgh, had already made a reputation by demonstrating the species specificity of peptide hormones, and he had set up a primate laboratory to study reproduction using a rhesus monkey model. A rhesus monkey was an ideal model: it had a 28-day menstrual cycle with a 14-day luteal phase and the hormone secretion was almost superimposable on the pattern in humans. Knobil was also developing the assays for steroids and specific assays for the peptide hormones in monkeys, which of course needed different assays than the ones for humans. Together, our group worked out the mechanisms that control the menstrual cycle estrogen-positive feedback, estrogen-negative feedback, and the role of gonadotropin-releasing hormone.
Were there any particular colleagues who you worked with who really influenced the path your research has taken?
Knobil really influenced the path my research took. He was a very meticulous man and was a very logical thinker. He really taught me how to question and design experiments. I think he has been a great help for many of his graduates in the field of reproductive physiology.
What do you consider to be the biggest achievement in your career so far?
There are many of which I am proud. First, there is the work I did after my fellowship in studying the corpus luteum, which we determined was present throughout pregnancy until the time of delivery. We also found that it made different products and was structured to make peptide products rather than just steroids, and that the corpus luteum was making steroids until delivery, but it was only approximately 1% of the steroids that the placenta made. We determined that it was making a peptide called relaxin, which was a hormone of pregnancy. We spent a lot of time working out the control of relaxin secretion, the production of relaxin, the conditions in which relaxin was present and not present, its structure, its actions in pregnancy, and reproduction in both females and males.
I also spent some time researching menopause, and I was one of the principal investigators in the SWAN study, which is probably the largest menopause grant. My role was to determine the endocrinology of the perimenopause and the changes that occurred when women went into menopause. Our hypothesis was as women age there is a gradual decrease in sensitivity/response to estrogen. Therefore, a child has very little estrogen circulating, but this is sufficient to suppress the pituitary hormones that stimulate the cycle. As the child ages and enters puberty, there is less sensitivity and the pituitary hormones regulate the cycle, stimulating the ovaries to make more estrogen, resulting in a regular menstrual cycle. However, as one ages, particularly over the age of 35 years, follicle-stimulating hormone, which is kept lower by estrogen, tends to rise. Ovarian reserve decreases and there are hormonal changes that are consistent with the lack of sensitivity. In menopause, there is even less sensitivity to estrogens. I really enjoyed working on this study and think it was a very big achievement of mine.
What do you think has been the biggest breakthrough in reproductive endocrinology research in recent years?
There are two ways to look at this: specific and nonspecific. Our understanding of reproductive endocrinology came about once we were able to accurately measure small quantities of hormones; this was what enabled us to determine what is going on in the menstrual cycle. Since then, there have been many advances in genetics and its associated technology (PCR, knockout animals, the ability to screen the genome, and so on). These have all greatly contributed to more knowledge. In reproduction, specifically IVF, which got the last Nobel Prize in physiology, has changed the course of management of fertility. Many of the changes that have occurred recently in IVF have only been small advances as groups have found better mediums, timings, and so on. Consequently, in women under the age of 35 years, a good program will give an approximate 50% success rate in terms of pregnancy on the first attempt. This used to be so much lower. Prior to this work, the first full-term pregnancy was on approximately the 185th attempt. The field will continue to improve in this manner because there is a lot we need to know: we need to know more about implantation and local control. When we understand the control mechanisms and what chemicals are involved, we will know whether we can produce agents to inhibit and stimulate an action, thereby improving results.
Could you tell me a bit about the research you are working on at the moment?
I am currently involved in a study in menopausal and perimenopausal women to determine the effects of age, menopause and no menopause on the development of arterial sclerosis in vessels, by looking at the thickness of the internal layer of arteries and the calcification in arteries and looking at arteries of the uterus. A fair number of women have hysterectomies, and we are using these hysterectomy specimens. It is a little early to talk about definitive results, but certainly there are minimal changes in women in their late 40s and early 50s who have had hysterectomies. However, once they are older, by 70 years of age, there is a higher incidence of calcifications in uterine vessels.
The prevalence of obesity is increasing, how does this affect infertility? Is obesity the biggest cause of infertility?
Obesity does affect infertility, but only in really obese women, women with BMIs >40. This is a major problem, but it affects a relatively small number of individuals. I don't think obesity has caused a percentage-wise increase in presentations of infertility. There are many causes of infertility, some of which are still unknown. For example, there are causes of infertility in men that are genetic, toxic or environmental and these decrease the quality of semen. In women, there are hormonal causes, such as polycystic ovarian syndrome, thyroid problems or increased secretion of the hormone prolactin, which will affect ovulation. There are anatomic problems that one is born with or can develop (such as fibroids, which may enlarge the uterus and distort fertility), or damage from venereal diseases or infections; even a ruptured appendix could effect the pelvic structures and potentially close the fallopian tubes. Age is another very important factor in the ability to get pregnant. Fertility decreases with age, to a dramatic extent over 38 years of age. Nowadays, many women are waiting until their 40s to get pregnant and are, consequently, having more difficulty. Therefore, more individuals require assisted reproduction: in the USA, IVF accounts for 1% of the deliveries. Overall, there are numerous factors to take into consideration.
Do you think ethnicity plays a big role in infertility & how the condition is treated?
There are two ways to look at this. On the one hand, there is specific biological difference between ethnic groups. For example, uterine fibroids are much more likely to develop in African women at a younger age, and the fibroids tend to be larger. This was demonstrated in the SWAN study. Some of these women will not be able to become pregnant because the fibroids distort the reproductive tract, thus, the uterus cannot retain a pregnancy until it is viable.
On the other hand, the link between ethnicity and infertility is indirect. If one is a member of an ethnic group, which in a society has a lower socioeconomic status and lower chances of advancement (this varies from country to country and area to area), you have a problem. These individuals are more likely to be undernourished, even malnourished, and they do not have the best healthcare to address this. Furthermore, they do not have the best income to provide themselves with nutrition. In addition, they may have greater despair as they see no chance of getting out of their situation. With despair comes behaviors that cause further problems: there is greater depression, illicit drug use and alcoholism. With lower socioeconomic status, there may be lower education levels, so one may not recognize the related problems, such as smoking. You will damage your health and certainly your fertility by smoking and shorten the time to menopause and ovarian failure. Overall, it is a more complicated question, but there certainly is a relationship, directly or indirectly, between ethnicity and infertility.
How important are clinical trials for women with fertility problems?
When a new agent is developed, it is tested in animals to see if it has the ability to work, and it is tested in humans for safety. Then randomized clinical trials are needed to ensure it works better when compared with not doing anything at all and that it does not cause any complications. Clinical trials are important for progress, without them we would not be able to use new agents safely, and progress in that area will stop. However, these studies require a lot of funding.
How important do you think it is to educate the public about infertility & its possible causes?
I think an educated public is a healthier public. The more you know, the more you can avoid doing things that are harmful. We are seeing phenomena now that are just being recognized. Lifespan seems to be increasing dramatically in the last 30 or 40 years by 20 years. It is not unusual for people to live well into their 80s now, and we are also seeing more individuals reach their centenary. This is a dramatic change. We do not know for sure why this has happened, but we can make a few guesses: better diet (more fruit and less fat), the elimination of smoking and more exercise; these are probably the simple things that have added years to an individual's life. It took a long time to educate people in this, and by no means is it complete. Individuals need to be responsible and avoid the agents that will cause them harm (e.g., illicit drugs, smoking and alcohol) or can be harmful for fertility and for the development of a baby. Consequently, education should occur early and repetitively.
Do you think there can be too much information given to the public regarding infertility & its causes?
The problem with too much information is people turn off. One has to be very careful. From a physician's point of view, as you see patients, theoretically, you should deal with getting rid of all their bad habits (e.g., smoking, poor diet and so on). However, this is a lot for the patient to take in. What you need to do for an individual patient is deal with the major problem. If someone is obese, that is what you deal with first.
Furthermore, not all education is equivalent. A lot of the information that is being given is erroneous or is presented in a confusing manner.
This is true when someone is trying to sell you a product. Patients are being sold this information but are not being educated, such as with taking large quantities of vitamins. Large quantities of vitamins are useless for most people. For example, approximately 10 years ago vitamin E was sold as the thing to take in high quantity. However, when the study was done, the vitamin E group had a higher death rate than the control group. Consequently, it's not planned education; there may be too much information for patients to accurately absorb. Patients should be taught the simple things that are known to be good for you and those that are bad for you to improve their fertility.
Where do you see the field of research going in the future?
My guess is we only know a fraction of what we need to learn. There is still so much we don't know in every area of women's health, so the field is wide open. For example, it is only in the last 20 years or so that we even understood how a hormone such as estrogen even works. Now we know we can control, inhibit and block it. This is very important, for example, in estrogen-dependent breast cancer.
The great thing about research is if you are lucky and do things right, even false tests can provide a lot of important data. My only fear is that governments don't appreciate how much money they save by putting money into biomedical research. They decrease health costs by improving therapies, eradicating poor therapies and even developing products that may in turn help improve the economy of the country. There are things that waste money but research is needed to prove that. To make money, you have to spend it.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Future Medicine Ltd.
Financial & competing interests disclosure
G Weiss is now serving on the Serelaxin Global Mechanism of Action Advisory Board, Novartis. G Weiss has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.