StorkNet interview with
Samuel Thatcher, M.D.
Author of
Making a Baby: Everything You Need to Know to Get Pregnant and PCOS: The Hidden Epidemic

Making a Baby Sam Thatcher, M.D., Ph.D., began his career in reproductive science in 1973 when studying the detrimental effects of aging on reproduction. This culminated in a Ph.D. in human anatomy/reproductive biology at West Virginia University, where he simultaneously received his M.D.

PCOSA year of post doctoral research was spent between Edinburgh and Johns Hopkins Universities. On completion of his residency training in obstetrics and gynecology at Yale/New Haven Hospital, he returned to Edinburgh University as Lecturer in Reproductive Medicine and Medical Director of the IVF program of Edinburgh University and the Royal Infirmary. He completed a fellowship in reproductive endocrinology and served on the faculty in the Division of Reproductive Endocrinology at Yale before returning to East Tennessee.

His research interests continue in reproductive aging, ovarian function, assisted reproduction and early human development. He is a member of over 20 national and international societies.

Visit Dr. Thatcher's website!

Samuel Thatcher, MD is a Reproductive Endocrinologist, specializing in reproductive aging, ovarian function, assisted reproduction and early human development. He is the author of two books and a weekly column on his website. Dr. Thatcher joined StorkNet to discuss infertility and Polycystic Ovarian Syndrome. Member questions and Dr. Thatcher's answers follow . . .


LIBIDO
Liz:
During my pregnancy, my libido was hyperactive. Also, I had increased hirstutism (something I suffer with normally.) After I delivered, my hirstutism became much less noticeable (even less than pre-pregnancy), however I was left with absolutely no sex drive. I went to my OB for help. He referred me to a sex therapist. The sex therapist feels my problem is biologically based. My OB is not cooperating and is not returning my phone calls or the phone calls of the sex therapist. I'm planning on finding another doctor, but I was wondering if I should call another OB, an Endocrinologist, or a Reproductive Endocrinologist?

Dr. Thatcher: The most important sex organ is between our ears, not legs. Having said this there are several endocrine reasons for lower sex drive including increased prolactin and low androgen levels. If your sex therapist believes it is biological, I would take this seriously.

I am not sure which variety of physician may be best for you. I would ask if they have not only specific training, but also specific interest in PCOS. It may matter less about their academic qualification than the willingness to sort through the problem with you.

STOPPING THE PILL AND STARTING A FAMILY
Heather: I was diagnosed with PCOS when I was 19 and was put on the pill to help regulate my cycles. I am 26 now, and my husband and I would like to try for a baby early 2001. I will be going off the pill in November. My question is, should I expect my periods to go back to being very irregular? Also, do women with PCOS ovulate at all? I don't know what to expect -- and I don't want to waste time trying to conceive when I should be put on some sort of medication right away.

Dr. Thatcher: I am a big supporter of oral contraceptives for those with PCOS who have no contraindications and do not want to be pregnant. Contrary to what many advise, I suggest trying in the first month off the pill. The chances of miscarriage may be slightly higher, but this may be the best chance for a pregnancy. It is surprising how many women say, "I had no problems getting pregnant the first time. It happened the first month off the pill." There may be a rebound effect and ovulation. I would not worry about temperature tracking or ovulation detection kits until you have demonstrated that you will have regular periods.

If a period does not begin after 45 days, it may be reasonable to perform a home pregnancy test. One of the best ways to regulate periods is with "natural" progesterone usually as the brand Prometriumô. Evaluation should be started including tests for insulin resistance if periods are not regular (26-35 days) after about 3 months.

GAINING WEIGHT
Candy: What can I do to stop gaining weight? My testosterone is really high but I am on clomid so can't take any medications that will harm a possible pregnancy. I have tried carbohydrates diet but because I am a fussy eater don't eat many items on that list. I also have a treadmill and a few free weights that I use regularly.

Dr. Thatcher: I know I will offend some with this comment, but weight is gained when the calories consumed are greater than the calories used. Weight is lost by either decreasing calorie intake or increasing physical activity. I believe this is an absolute truth. HOWEVER, I am convinced those with PCOS utilize calories differently. Many with PCOS have high insulin levels. With increased insulin the body is programmed to hold on to every calorie and store them as fat. As weight increases, insulin increases, and then weight increases more. It can be a hopeless spiral down. It would be great if you could find a nutritionist who could help you analyze and possibly improve your eating habits. Some may find help with metformin and I believe an evaluation for insulin resistance can provide an important insight into PCOS and its therapy.

STARTING BACK FERTILITY THERAPY AFTER SUCCESSFUL PREGNANCY
Michele:
I have PCOS and we got pregnant using fertinex. My cycles seemed to become more stable after having our son, and we want to try again. Should we go right back to fertinex, or, since I seem to be have somewhat regular cycles, should we do something else? Time is an issue. I am 38 now.

Dr. Thatcher: I have two conflicting statements. The first is that I go back with what has worked in the past. Fertinex or Gonal-F would be a good place to start. The second is that with the new insulin altering drugs and possible improvement in your ovarian function after pregnancy, you might take a less aggressive first step. Cycles tend to become more regular in PCOS between 35 and 45, but this is also a period of fertility decline. Your age is a concern and would cause me to be more aggressive. One of the first steps in your evaluation should be a FSH and Estradiol level on cycle day two or three.

"LOW CARBING"
Liz:
Do you recommend a low-carb diet for woman with PCOS?

Dr. Thatcher: Many with PCOS have success with low carbohydrate diets. Terms such as glycemic index have been employed to explain the capacity of certain foods to increase insulin. I believe that most low carbohydrates diets are mainly calorie restrictive diets and this is why weight is lost. The goal should be balanced good nutrition. A reduction of 250 to 500 calories a day in addition to a modest increase in activity can have very positive benefits for most with PCOS. "Diets" as such are almost always doomed to fail and "yo yo dieting" can have negative health benefits. The key is lifestyle changes that can be maintained forever. We usually aim at about a 10% weight loss as a realistic goal for most.

INSULIN ALTERING DRUGS
Michele: What is the current thinking on the best treatment of PCOS? The doctors I have seen always recommend either birth control pills or Clomid (if I want to get pregnant). It seems like there must be something new out there!

Dr. Thatcher: At least 50% of PCOS appears to have a component of abnormal glucose tolerance, increased insulin or insulin resistance. In part by accident, it was stumbled on that insulin-altering drugs generally used in the treatment of diabetes were successful in regulating periods, promoting ovulation and increasing fertility. These drugs have not received FDA approval for this use, but have become widely employed. We now have a therapy that actually treats the cause of PCOS rather than just overpowering or suppressing it. The principle first line therapy is metformin (Glucophage) which often has the benefit of weight loss, but has GI side-effects. The second group of drugs include Actos and Avandia and directly reduce insulin. The success of these agents seems to be at least as good as clomiphene and sometimes work when all else fails. Still, they are not perfect and should be discussed in detail with your physician, and best used after appropriate lab testing.

PREGNANCY WITH ELEVATED FSH LEVEL
Penny: I was diagnosed with possible ovarian depletion in summer '98 (FSH of 11.9-13: other values normal) at the age of 40. With the help of alternative therapies, I got pregnant in a couple of months, just before I was to start Gonal-F treatment. I've never been sure if my original diagnosis was too doom-laden, if I turned it around with my own research and treatment (my cycles certainly became longer and my periods much fuller), or if I just got really lucky. I have a beautiful son of 18 months, who is still nursing heavily, including at night. I have only recently returned to regular cycles, and my question is: has the prolonged amenorrhea (over two years including the pregnancy) done anything to preserve whatever fertility I have left? In other words, can I assume that I am more or less where I was two years ago? I ask this because I am 42.8 and would love to have another child, but my husband has no interest in trying for one till his professional life (and our financial situation) turns around. I can't seem to get a straight answer to this question - maybe there isn't one! Thanks for your input.

Dr. Thatcher: An elevated FSH, which yours was, does not exclude a pregnancy, just predicts the response to ovarian stimulation with medications. The body attempts to preserve ovulation for as long as it can. With massive amounts of fertility drugs still you may have only ovulated a single egg. Your story is not uncommon, but unfortunately, the miscarriage rate is increased. Obviously, you were smiled upon. I would repeat the FSH level. I do not know of significant risks, other than financial, of fertility therapy, but it may be a rough trip emotionally and one you might decide to avoid.

THERAPY FOR LOW SPERM COUNTS
Nancy: My husband has a very low sperm count. Luckily, we were able to conceive naturally last winter. Do you have any suggestions to increase our chances of this happening again in the future. This pregnancy took 6 years to come even with 2 AI attempts.

Dr. Thatcher: I might suggest cycle tracking with basal body temperature (BBT) and ovulation prediction kits (OPK). Recent research has shown that properly timed intrauterine insemination (IUI) can also be of value. Your chances of pregnancy after assisted reproduction (in vitro fertilization IVF with sperm injection ICSI) may be excellent, but this is a completely different story.

TUBAL STERILIZATION REVERSAL
Kim: Once a woman has a tubal ligation, is there any way of reversing? Is there a time limit when it could be successful? What are the statistics for having children after a tubal reversal?

Dr. Thatcher: Tubal sterilization reversal is certainly possible in many cases, but it is a lot more difficult than the initial sterilization procedure. It usually involves an abdominal incision a prolonged surgery using the operating microscope and a 3-6 week recovery period. An alternative that some may choose is in vitro fertilization. Clearly do your homework well and feel very comfortable with your decision and physician.

The procedure is usually expensive and often not covered by insurance. An all inclusive cost is $6000 to $10000. A small number of centers are doing the procedure through the laparoscope, which may be less expensive, and avoids a major operation. While an excellent procedure, there are only a small number surgeons performing the procedure at present time.

Please make sure your surgeon is well experienced and is performing a relatively large number of these procedures. Know his/her honest success rate. The best seldom charge more. Success rate for pregnancy may be 50-75% over the first year after surgery. There will be a risk of ectopic pregnancy (10%-25%) after the procedure and a need for additional contraception after a pregnancy.

CYCLE REGULATION
Dez: I have PCOS, however I am not overweight or have a facial hair problem, so I went undiagnosed for years. The only tell tail sign was having no regular cycle (perhaps 1-3 periods a year). I conceived my daughter with metformin (clomid did nothing for me). Now I want to conceive again. I'm sure I will have to use Metformin again. My question is, IS there any way I can get regular fertile cycles back without the pill or using metformin in the short term? If not, will this mean that I will never have regular periods?

Dr. Thatcher: Unfortunately, PCOS is for life. The pattern of menstrual cycles is very individualized and is impossible to predict. We know that periods tend to become more regular after age 35. Periods often become more regular after pregnancy, but this didn't seem to work for you.

Generally, I believe it is better to have periods than not. One direct and proven benefit of regular menstruation is a reduction in uterine cancer. A alternative minimalistic therapy which usually does not impede fertility, and may promote it slightly, is the periodic use of oral progesterone. This may be preferred over Medroxyprogesterone acetate that you have probably used in the past.

In at least one way, you are lucky that metformin did so well for you. However, because it worked this may be an indication of insulin resistance and therefore, you could be at higher risk for type 2 diabetes. Trials are underway to see if long term metformin may protect against development of diabetes. We do not know the answer to this question. Perhaps, you should not consider metformin only as a fertility agent. A good sit down with your physician to discuss the options may be in order.

BREAST FEEDING AND FERTILITY
Paige: I am almost 37 and am currently breastfeeding my 9 month old daughter. There is a 6 year gap between her and my middle child although my husband and I did nothing to prevent conception. My first two children were conceived very easily. I have not yet had a return of my menstrual cycle. My husband and I are currently trying for our fourth child and have been since my daughter was 2 months old. Is there anything that can be done to induce ovulation in a breastfeeding mother without weaning?

Dr. Thatcher: Lack of ovulation and poor uterine lining can often accompany breastfeeding at least initially, and have been a very important mechanism for our survival in the past. To be pregnant and breast feeding is perceived to be too taxing and therefore the body in its wisdom inhibits ovulation. The evolutionary mechanism does not take into account our capacity to go the food market and buy the food that we and our offspring need.

I gave you this long introduction instead of just saying "no." There are very few drugs proven safe during breastfeeding. I guess progesterone could be used for menstrual regulation, but check with your physician. Even this natural hormone is secreted in breast milk, although in probably inconsequential amounts.

FINDING PCOS PHYSICIAN
Michelle: Is there a resource for finding the best local doctors, who are up on the latest PCOS treatments? Not just for fertility, but to manage it on an ongoing basis?

Click to orderDr. Thatcher: Unfortunately there is no organizational listing for physicians experienced in treatment of patients with PCOS. Sometimes several physicians must be interviewed. Good suggestions are sometimes possible through the chat rooms of Polycystic Ovarian Syndrome Association, who also has a listing of physicians that have been self-identified as having an interest in PCOS. The following is an excerpt from the chapter in my recent book that partially addresses this concern.

"Because the symptoms and physical findings vary and because not every patient presents with the same symptoms, the diagnosis of PCOS is often missed. Only in the last few years has medical research been able to make connections between a metabolic endocrine disorder and disturbances in multiple body systems. PCOS is challenging to physicians trained to diagnose and treat specific, well-defined diseases. PCOS patients enter the physician's office often with a collection of vague symptoms and with a problem that, even when diagnosed, the lack of curative treatments is frustrating. Although all the dots are there, not every physician is able to connect all dots that forms the image of PCOS.

A woman may begin to experience some symptoms of PCOS at a very young age She may have been overweight as a young child and the pediatrician may have told her mother to simply watch her diet. In her teens, she may have sought medical help for acne or excessive facial hair and her dermatologist offered creams or electrolysis as treatment. In her twenties, perhaps still overweight, she may have sought help from her gynecologist for irregular periods and been given a package of birth control pills. In her thirties, an inability to conceive may have sent her to a fertility specialist where she was given medication to control ovulation.

Unfortunately, our culture often discriminates against overweight women. It is a sad fact that many physicians are also prejudiced against these women, assuming them to be lazy or lacking self-discipline. These doctors often dismiss these patients, telling them to simply go home and lose some weight.

Years of seeing one doctor after another while her symptoms often compound rather than subside is disheartening. There is the perception and often the reality that valuable time has been lost while going from one doctor to another. Self esteem may drop as weight and frustration rise. Blood tests or ultrasounds that would lead to a definitive diagnosis of PCOS are not done. The bottom line is that each of these medical specialists has treated a small aspect of the problem, but none has put all the pieces of the puzzle together as PCOS.

Physicians should not consider themselves, nor should their patients consider them to be infallible. Patients must ask questions and communicate honestly with their physicians. Confidence in the capacity to live better with a chronic condition is one of the greatest tools in the struggle with PCOS. There may need to be an extensive search to find a doctor that is truly knowledgeable about PCOS. This physician may be a primary care provider, but more often will be a gynecologist, endocrinologist, or reproductive endocrinologist who has experience treating PCOS and is well informed about new research areas.

For women with PCOS, the decision about whom to choose to provide medical care is critical both to present physical wellness and long term quality of health. Seeking a doctor who has a strong base of knowledge about PCOS and who understands present treatment is quite a challenge. Many doctors simply do not have the time to keep up with the latest research about the syndrome, especially, if they are in a practice where they do not see large numbers of patients with PCOS. And some doctors, unfortunately, just aren't interested in gaining further knowledge or offering new treatment options. Furthermore, managed care/insurance providers have a strong influence on what direction many women take in getting care. For these reasons, the key to being a smart consumer is to become as educated as possible about PCOS, and gaining a good understanding of the arena in which you are seeking care.

Being a passive or non-participatory patient doesn't work with PCOS. In the hands of a less than knowledgeable or uninterested care provider, there can be an escalation of symptoms resulting in the development of diseases such as endometrial cancer, diabetes or possibly heart disease. Finding quality care is imperative for all women with the disorder.

ARE FERTILITY DRUGS NECESSARY?
Sabra Ellen: I have a preliminary diagnosis of PCOS. I have read so many contradictory things about it, and nothing cheerful. I am wondering . . . is it possible/likely to get pregnant with PCOS without taking fertility drugs? I do not believe in them, but it seems that all the women I encounter with PCOS wind up using something like Clomid (which some sources say works and others say doesn't really) to get pregnant. And if it is, what would be a reasonable time frame? One year? Three?

Dr. Thatcher: First, I recommend that you have a "sit down" with a physician familiar with both PCOS and infertility to discuss options. This is usually a reproductive endocrinologist. It is very difficult to obtain a foundation of information about either fertility therapy or PCOS from a collection of life experiences. None of these individuals are you. There are excellent studies form Australia that suggest that those with PCOS who are also overweight have an excellent chance of establishing normal menstruation and pregnancy by lifestyle alterations alone. As little of a 10% decrease in body weight associated with a modest increase in physical activity may be all that it takes. Clomiphene is a good drug, but not a great drug. Of course some with say that it works and others will not because that is the truth. It is about 30% effective in establishment of pregnancy. The drug is a good first line therapy. It is relatively easy, safe, and cheap. The chance of twins is about 5%. Over 70% of pregnancies established on clomiphene are in the first 4 cycles of use.

INSULIN AND INSULIN RESISTANCE
Becky: I have PCOS and my insulin level is 11. Is that enough of a resistance to be able to take metformin?

Dr. Thatcher: A fasting insulin level of 11 is not considered elevated by most. While some use 10 as a cut off level, many, many individuals have levels this high and are otherwise normal. Most who are overweight will have levels over 10. Almost all experts consider a level of over 20 as abnormal. I personally use 14, but there is no hard fast rule.

When the fasting insulin level is elevated, that is called hyperinsulinemia. Hyperinsulinemia is a marker of insulin resistance, but it is not the same as insulin resistance. There are a variety of tests that are used to measure insulin resistance. One test is the insulin level obtained during a glucose tolerance test.

Also, what is insulin resistance anyway? Insulin resistance can be thought of as deafness. The best way to explain insulin resistance is that the organs that use insulin grow increasingly hard of hearing, in order to compensate and keep the lines of communication open the pancreas, where insulin is made, starts to speaks loud and louder. Insulin resistance is deafness not to sound but to the action of glucose and insulin.

Now, when to be treated. This is a very controversial topic. Insulin resistance is clearly linked to increased risk of developing of type 2 diabetes. Insulin resistance is also clearly related to abnormal ovarian function and increased levels of androgens. However insulin resistance is not a disease as such. Some advocate a trial of insulin altering drugs in almost all those who do not ovulate. Others reserve therapy for those that have clearly been shown to be insulin resistant. Pregnancies have been reported after use of insulin altering drugs, such as metformin, when the insulin levels are completely normal. This is a decision that is best made in cooperation with an individual physician well versed in PCOS and insulin altering drugs.

BREASTFEEDING AND FERTILITY
Janet:
We have one child who is 17 months. I nursed him until he was 14 months. We have been trying to get pregnant since he was 6 months old, right around the time my menstrual cycle returned. That is almost a year now. I am wondering what affect the nursing would have had on my fertility, and if that would be part of a reason we are having such a hard time getting pregnant this time? Last time it was really quick.

Dr. Thatcher: I would say yes, this is why you are not pregnant. One should expect a 6 month gap after feeding is completely discontinued before any concern. That is, unless you are using breastfeeding as a contraception. Then it always seems to occur immediately. Also, see the comments posted earlier.

METFORMIN USE IN DIABETES AND INFERTILITY
Theresa:
I would like to know about metformin being used to help with fertility in women with PCOS? I was told four years ago I had PCOS and I am also a type two diabetic and have been told I will need insulin injections instead of metformin. I am on diabex (500mg) three times a day. Any information you have would be a great help.

Dr. Thatcher: I am not trying to evade the question. I do not like to give contrary information, and there are many "right ways." Having said this, I believe Metformin to be a foundation of the treatment of type 2 diabetes, regardless of pregnancy desires. The first evidence that metformin was useful for infertility came form the accidental finding that diabetics using metformin began to have regular cycles and get pregnant. We are hopeful that diet, exercise, and insulin altering drugs will be able to keep the thousands off insulin. You may also want to check out the American Diabetes Association site which has a load of good information.

HOW LONG CAN EMBRYOS REMAIN FROZEN?
Robin: I recently gave birth to my son, Brett. He was a product of IVF with ICSI. I have about 9 frozen embryos. My question is: What are my chances of conceiving another child/children, with the frozen embryos? IS there a life span if they are frozen? Can I go a natural cycle, or do I need to do Lupron again? The infertility was due to male infertility.

Dr. Thatcher: Not trying to pass the buck, but these are questions that should be easily and best answered by your IVF center. Success rates with frozen embryos are center specific. It is never quite as good as fresh, but the fact that it appears that it was primarily a sperm issue, should get you quite good chances of success - if your cycles are regular and especially if you ovulate on your own. Many centers do transfers with any form of stimulation or suppression. It's very easy, you monitor the cycle and stop by the first transfer. No one knows how long viability remains for frozen embryos. There have been successful pregnancies after 10 years. All agree the quicker out of the freezer the better, but this is largely for other reasons than the health of the embryo.

WILL FERTILITY DRUGS BE NEED FOR A SECOND PREGNANCY?
Anna: I have PCOS and now I'm pregnant with my first child, with help from Clomid. My questions for you are: Do I have a chance to conceive without help from medicine in the future?

Dr. Thatcher: Sometimes a second pregnancy will follow the first without any additional help. It largely depends on whether ovulation will more likely or more frequently occur. You should not think that you are either infertile, or that you might not need additional therapy. The fact that you became pregnant after clomiphene suggests that your ovulatory disturbance was not too severe. If you do not want to become pregnant and have stopped breastfeeding, I usually suggest oral contraceptives. Do not wait, but try to become pregnant the first month off the pill. The miscarriage rate may be slightly increased, but so is the pregnancy rate. Try to keep weight down and exercise up. This will go a long way toward improving fertility.

DOES CLOMIPHENE / PCOS CAUSE BIRTH DEFECTS
Anna: Is there an increased risk for birth defects for my baby since I've got PCOS?

Dr. Thatcher: There have tens of thousands of pregnancies on clomiphene. The rate of birth defects does not appear to be increased. Birth defects occur in about 1% of all pregnancies.

I strongly believe that there is an increase risk of miscarriage with PCOS. There is also an increased risk of pregnancy induced hypertension (pre-eclampsia, toxemia) and gestational diabetes. Each of these can cause major problems with pregnancy. I do not know that PCOS itself has any DIRECT link with birth defects. In the past PCOS patients have been so poorly studied in this area that a conclusion cannot be made.

EXERCISE IN PREGNANCY
Tara: Can you do sit ups while you are pregnant (1st trimester)?

Dr. Thatcher: I am not sure of the answer to this specific question, but I generally would not recommend it. I usually advise to change from strength and aerobic conditioning to mobility and flexibility. Yoga is excellent. Exercise is important in pregnancy, but aggressive exercise may shift the needed blood flow, thus nutrient supply, to skeletal muscle and away from the uterus. There are several good books on exercise in pregnancy available.

ABNORMAL FETAL ULTRASOUND
Michael K: Our doctor has informed my wife and myself that our baby (24 weeks) has dilated kidneys. They have sent us for a fetal echocardiogram which was negative and have now done an amniocentesis. The results should be back this week. On Monday 9-25-00 we had another sonogram and one of the kidneys has gotten better. He has explained to us what might cause this and what might have to be done, early delivery if the problem gets worse. I was just looking for another opinion on what might cause this and what our options are.

Dr. Thatcher: This is too important a topic for Internet consultation. If you do not feel your questions have been adequately answered seek a consultation with a specialist in maternal-fetal medicine. You physician should be very willing to refer you. All my best to you.

DELAYED OVULATION
Lisa: Any idea what is going on here? I had fairly regular cycles of 32-34 days. I charted temps for one cycle just before starting to try conceiving (IUI) and it looked picture perfect. Even had the small temp dip before ovulation. Then the next cycle, when I was going to try I had a 52 day cycle with no ovulation. Then this cycle I am on day 23 with no ovulation so far (am using OPKs and temping) but have had lots of clear egg white cervical mucus for over 12 days so far. Any ideas?

Dr. Thatcher: The average cycle length is 28-29 days. The farther one deviates from the norm the greater the likelihood of poor egg quality, lack of ovulation. Delayed ovulation is also associated with an increased risk of miscarriage. The rate of infertility is very high when cycles are over 35 days and I do not even recommend testing for ovulation, just progressing with therapy. At 32-34 days you may be somewhat borderline for normal ovarian function. Then too, there could be other problems such as male and anatomic factors. Still my first thought with the above scenario is that there may be an ovarian/ovulation problem.

RECURRENT PREGNANCY LOSS
Laura: Can you send me info regarding ''rejecting the fetus?' I have been having miscarriages (8 of them) over the past 7 years. I live in Edmonton Alberta Canada, and the doctors here don't know why. I went to Florida for a vacation and went to a hospital with another miscarriage. The doctor said that I reject the fetus. The doctors in Edmonton don't agree, and say it's very unlikely. But it's some hope for me. Can you help?

Dr. Thatcher: My list of reasons of miscarriage in the first trimester in order of occurrence and with percent of occurrence follows. This is only my own estimate. 1) Endocrine/genetic 70% 2) anatomic/ structural 2O% 3) inherited genetic 5% 4) other including infection, immunologic, and chronic maternal medical problems 5%. Your case is much too complicated and I have much too little information about the pregnancy losses to even guess at a cause or quote a statistics for the risk for an additional pregnancy. I am not a large proponent of the immunologic causes (rejection) of pregnancy loss. I am sure that it occurs, but I believe it is very uncommon. I mostly favor hormonal causes related to egg quality and structural causes that are usually diagnosed by ultrasound and hysteroscopy.

METFORMIN WHILE BREAST FEEDING
Jenine: I am currently 8 months pregnant. I have PCOS and conceived while using Metformin. I've been on it throughout my pregnancy and thankfully I've had an uneventful pregnancy. I want to know if it is ok to stay on the met while I breastfeed or should I go off it until I stop breastfeeding. What are the dangers of staying on Met to the baby while breastfeeding? Thank you so much!

Dr. Thatcher: Metformin is released in breast milk. Most recommend not using Metformin while breastfeeding, although there is no specific research studies that Ii know of indicating that it will be of harm.

CLOMIPHENE USE
maddie: I quit ovulating for six months and my RE could find nothing wrong with my reproductive system. He concluded that my being overweight was the reason for my non-ovulation. He put me on Clomid which worked but I did not like the side effects. I am stopping the Clomid this month and hoping to conceive naturally. Is there any reason to think that since I ovulated on Clomid, my cycles might return to normal?

Dr. Thatcher: Not impossible. Usually clomiphene is effective only in its cycle of use. Sometimes its effects will hold over until the next and it is not unusual for a pregnancy to occur in the first month or two after clomiphene is stopped.

Unfortunately, the nest step up from clomiphene is usually the injectable medications. Some report the side effects are less than clomiphene, but they are certainly more costly, and more risky.

In my experience, those that are overweight do not ovulate and have a normal hormone values by our usual diagnostic testing are often insulin resistant. You might benefit form metformin, or at least a trial. I know you do not want to hear this from anyone, but lifestyle improvements in diet (that's not the same as dieting) and increased physical activity (that's not the same as strenuous exercise) can be very helpful.

WHEN DOES PCOS START?
Carlene: I am 21 years old. I have had irregular periods all my life. Then I got on the birth control pill in December of 99. I got off of it in April because of weight gain. Since then my periods have stayed regular, except for this month where I just have a lot of spotting. My mother says I may have PCOS because since getting off the pill, I haven't gotten pregnant yet. My mother had one child at 19 and then had trouble having any more. She got on Pergonal and was able to conceive after that with no trouble. My sister had a cyst on her ovaries removed. Does any of this indicate to you that I may have PCOS?

Dr. Thatcher: We believe that PCOS is inherited. This means you may have had the gene for PCOS since before birth. It sounds like your mom could have easily had PCOS and it sounds like you may too. The chance of passing from mom to daughter is probably about 50%. PCOS can also be inherited through the dad's side, but there is probably no clue that it is there other than an increased risk of diabetes in some. The genetics of PCOS is an important area of present research. If you are concerned, you may want to see a physician who specializes in PCOS.

METFORMIN AND BIRTH DEFECTS
Theressa: Will metformin (diabex 500mg) cause birth defects? I take metformin for type two diabetes and I also have PCOS. (6Yrs)

Dr. Thatcher: There is a clear relationship between how well the blood sugar levels are controlled and the risk of birth defects and overall complication in pregnancy outcome. Blood sugars must be normalized before a pregnancy is attempted.

Metformin is listed as "pregnancy category B" by the FDA. This indicates there is no known relationship with birth defects, but also that it is not proven to be safe. If you have type 2 diabetes and are using metformin, it may be reasonable to continue because pregnancy often worsens insulin resistance. Pregnancy planning clearly needs some advanced thought and conversation with your endocrinologist and possibly a maternal fetal medicine specialist.

REGULATION OF MENSTRUAL CYCLES BY METFORMIN
Robin: I haven't been officially diagnosed with PCOS, and I'm neither overweight or have excess hair or diabetes, but I've been prescribed metformin and it made me have a normal cycle for the first time in 16 months (I did not respond to Clomid). My question is: when the metformin is working for me, do you think it's possible that I have a mild case of PCOS?

Dr. Thatcher: The experts can't agree with what PCOS is. SO sure, you could have it. The largest single cause of lack of ovulation lies along the PCOS spectrum. It seems that about 50% of those with PCOS are insulin resistant and insulin resistance leads to lack of ovulation. Often insulin resistance will be missed on the routine lab testing for PCOS. I pay considerable attention to the ultrasound appearance of the ovaries. I bet there is an increase in small follicles (cysts) less than 10mm., or an increase in the size of the ovary. The fact that your cycles have regulated is great news. Hopefully a pregnancy is not far behind.

IS THERE A GENERIC METFORMIN
Theressa: Could you please tell me is there any difference between Metformin (Diabex) and Metformin (Glucophage)? I have read a lot about women being told to try Glucophage to help them get pregnant. I am on Diabex and would also like to conceive my third baby.

Dr. Thatcher: Diabex is another brand of metformin. Glucophage is a brand of metformin. Generics are on the way and will lower cost of the medication use.

METFORMIN USE IN PREGNANCY
Donna: I just found out that I am pregnant. I've been on glucophage for 2 months. I would rarely have periods, so I expected that the glucophage would help with periods. I was very surprised to find out that I had conceived so soon. My question is do you think it is safe to stay on the medication while pregnant?

Dr. Thatcher: There is very limited information on this. One study has shown a decrease in the rate of miscarriage in a relatively small group of patients. Another study also reported no problem when used during pregnancy. In the future, metformin may be widely used in pregnancy, but its use can not be universally recommended at present. We just do not know the risks. Hopefully this issue will be cleared up in the near future. A decision should be made in conjunction with advice form your obstetrician.

PCOS GENETICS AND THERAPY
Ngaire: I was diagnosed with PCOS several years ago. I have many classic symptoms - weight gain, excess hair, insulin resistance, annovular periods etc. My OB suspects that I have always had it but that the development of the symptoms was triggered off by my first pregnancy, as until then, I had no symptoms other than irregular periods. I have three children, the last of which required clomid to induce ovulation as I have had less than a period a year since the birth of my second son 5 years ago. With each pregnancy my symptoms get worse. I guess I have several questions - is it likely that my PCOS is indeed getting worse with each pregnancy? Is there any alternative to drugs (eg metformin) to control it? We are wishing to get pregnant with our last child but I am reacting negatively to the clomid dose required to induce ovulation (50 mg). So are there alternatives to this? As I am now 33. We wish to conceive fairly quickly - is there anything else we can do? And possibly most importantly - my mother is into alternative medicine and has suggested that I could restore my cycles with the use of 'natural' progesterone cream as suggested by Dr. John R Lee. What are your thoughts? I would appreciate any answers you could give me. Thanks. Ngaire

Dr. Thatcher: I would agree with your OB that you may have always had PCOS. It is a genetically based disorder. I am not sure about whether it was your pregnancy, or equally likely was that it was age and often weight that brings PCOS to the surface. Since PCOS can be altered by environment, I would strongly suggest that you encourage the very healthiest lifestyle in your children. They may not be able to escape the gene(s), but it is possible to alter their consequences by the changing the environment. Hopefully this indirectly answers a part of your questions.

I would concentrate on establishing and maintaining the healthiest possible lifestyle. Maximize nutrition (without dieting); increase physical activity without stressing yourself. Small investments can pay major dividends.

Metformin may be a good alternative, especially since you state that you are insulin resistant.

I am very cautious about recommending supplements. It is not that they may not work, in fact, it is that I have too much respect for them to idly prescribe herbs and supplements without a firmer scientific basis of their positive actions, and most importantly possible negative actions.

DELAYED OVULATION AND THE LUTEAL PHASE DEFECT
Candy: I have been using the basal thermometer for temping this cycle and have discovered (along with charting all babymaking encounters for the past 5 months, as well as cervical mucus) that I am not ovulating until cycle day 19. However my period begins on day 27 or 28. Am I looking at a luteal phase defect and if I am, what is my first choice of treatment? I am almost 38 and do not want to just try for another year after trying for almost 6 months now. Could the problem be in the first half of the cycle if signs point to the fact that I am ovulating or is it more likely that the problem is just too short of a luteal phase and therefore implantation is unlikely? What questions and information should I take to my doctor? Thank you.

Dr. Thatcher: I do not believe in the luteal phase defect as such. I believe that most defects of the luteal phase are in fact defects on the follicular phase. This may seem to be splitting hairs, but it puts the emphasis back on the developing follicle and egg and not the resulting corpus luteum and progesterone production. Good luteal phases follow good follicular phases. Conversely, if ovulation is delayed, the luteal phase is often inadequate. Yes, I think that implantation could be less likely because I believe egg quality is decreased.

Depending on a more complete history, you might be a candidate for clomiphene therapy. Hopefully it would promote a more timely ovulation. The good news is that a late ovulation, is miles above no ovulation and you might need just a little help to push you over the top.

WHY MAKE THE DIAGNOSIS OF PCOS?
Kendra: I have not been diagnosed with PCOS and do not have some of the more definitive symptoms. However, I have struggled with acne (present on the paternal side of the family) and increased periareolar hair growth. The hair growth was alarming to me and happened over a three year period. I am not over weight for my height and I have regular monthly menstrual periods. I have never used birth control pills. I asked my OB-GYN if I could have PCOS. She informed me that since I was having regular periods she doubted that I had PCOS. She further explained that in my case periareolar terminal hair growth was familial. She checked my testosterone and DHEA level (both results were WNL). I asked my mother if she had hair growth on her chest and she does not. Should I have a LH:FSH ratio done? Is a pelvic ultrasound indicated? If I am having regular menstrual periods, does this mean that I am ovulating monthly? Thank you for responding.

Dr. Thatcher: The strictest diagnosis of PCOS requires both hyperandrogenism, either by clinical signs or hormonal determination and anovulation, which usually translates into irregular cycles. The principle skin signs of hyperandrogenism are excessive hair growth (hirsutism) and acne. Adult acne is a reasonable reliable indicator of hyperandrogenism; hair around the nipples (periareolar) is not unless accompanied by hair in the middle of the chest and lower abdomen. It seems that in your case there may be mild "clinical" hyperandrogenism without laboratory confirmation. This occurs in at least 50% of cases. If so, it sounds like it came from your dad's side of the family. I would not be at all surprised that the ovaries were also at least mildly polycystic on ultrasound scan.

Oral contraceptives may help the acne by reducing luteinizing hormone and decreasing androgens. Even though your laboratory values are normal, there may be an increased sensitivity of the skin to androgens, and reduction may be of benefit.

It is possible that you may not be ovulating despite regular cycles. This is most important if fertility is an issue.

Whether you have PCOS is in some ways unimportant. The reason to make the diagnosis is most importantly a way to explain of a clustering of signs and symptoms and identify health risks. We direct therapy not at PCOS, but at its signs and symptoms. Of course the diagnosis of PCOS also may identify with a long-term outlook toward possible metabolic consequences.

The fact that you have regular cycles and do not have a weight problem probably removes many of the risks associated with PCOS. It may be of academic interest to determine the LH/FSH ratio, but it probably would not affect anything written. As a part of good health maintenance it may be prudent to have a lipid profile, fasting glucose and maybe insulin level. If there is a strong family history of type 2 diabetes even a glucose tolerance test with insulin levels. This may identify the risk of diabetes and possibly heart disease and promote life-style changes, even medical intervention that might allow a longer and healthier life.

METFORMIN AND WHEN TO START OTHER FERTILITY THERAPY
Kris: I am 26 and have recently been diagnosed with PCOS. I have a 16 month old daughter that was conceived with fertinex. I have been having regular though light periods since April, but have not ovulated. I am taking 1500mg of glucophage a day. How many cycles should I wait before adding fertility treatment to the mix? My doctor is in a hurry, but I would like to get my system in order first and see if I ovulate on my own.

Dr. Thatcher: I usually will try clomiphene challenge in the 5th or 6th month of metformin. Some individuals who have been previously clomiphene resistant will ovulate and become pregnant on the metformin-clomiphene regimen, when neither alone is sufficient.

It is usually the patient and not the physician that is in a hurry. If you are making positive lifestyle alterations and are feeling better, plus starting to have regular cycles, what's the rush? At 26 and with one successful pregnancy, your chances for another pregnancy are very high. The drug companies will make sure that there is plenty of gonadotropins whenever you might need them.

PCOS AND GETTING OLDER
Vicki: I've never actually been diagnosed with PCOS. But after reading what I have on the subject, I'm really starting to wonder whether this may have been the cause of all my past fertility problems. My question to you is that since I'm now no longer trying to conceive (I had a tubal ligation done after our last child), and if indeed I am correct on my assumption and this is PCOS, how will it continue to affect me as I get older? I am now 33.5 years old. (shortened version of question)

Dr. Thatcher: First, I agree that a good case could be made for your diagnosis of PCOS. One of the most pressing issues about PCOS is that there are its long term consequences. We virtually know nothing about this at present and the scattered reports tend to be conflicting.

There are several things we think we know for sure. PCOS is clearly associated with an increased risk of type 2 diabetes. Continued vigilance on fasting glucose levels, possibly even insulin levels may be a reasonable idea. Much of type 2 diabetes is weight related. It has been difficult to separate out the adverse effects of weight from other medical conditions.

PCOS patients also tend to have abnormal lipoid profiles and yearly monitoring with lifestyle, and possible medical intervention when appropriate. There is a real question about heart attacks and heart disease. It seems that the risk with PCOS should be much higher than it actually is. This is still an issue that requires a considerable amount of research. Both diabetes and heart disease may be preventable in part and successfully treated when identified in the formative stages.

There is a clear association of PCOS with cancer of the uterine lining (endometrium). This is markedly reduced and possible reversed with cycles regulation or regular bleeding. Others cancer such as ovarian and breast do not seem to be increased. Childbearing and oral contraceptive use is protective against ovarian cancer. Family history is most important issue with breast cancer. Routine mammogram and self-examination are strongly suggested. Colon cancer risk rise with obesity.

Cycles tend to become more regulate after age 35. It is possible that the menopausal transition is easier with PCOS. Hip fracture and osteoporosis are very significant health risks to postmenopausal women. Bone density is greatest and fracture risk appears reduced with PCOS.

StorkNet: Our deepest gratitude to Dr. Thatcher for taking so much time to talk with us. He tells us that he would like to come back again in a couple months. We will be contacting him so please save your questions and watch for announcements. Much more information about these subjects is available in Dr. Thatcher's books, listed above. Click on the book covers. Thanks to our StorkNet members, as well.

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