In Memory of the Perfect Imperfect Pregnancies

Pregnancy Loss Remembrance Day – October 15, 2012

Craig R. Sweet, M.D.
Reproductive Endocrinologist
Medical and Practice Director
Specialists in Reproductive Medicine & Surgery, P.A.

Over the Past 27 Years:

Starting my OB/GYN residency in 1985 with completing my fellowship in reproductive endocrinology, infertility & genetics in 1991, I can recall hundreds of pregnancy losses over the past 26 years. There were so many tears, emergency D&Cs, and especially, so many unanswered questions in the tear-filled eyes of my patients.

Nearly all of the women seemed to blame themselves. They felt it was something they did wrong. Perhaps it was the sex they had with their partners. Did they cause the loss by not resting enough? Did they worry the pregnancy into destruction? Was it punishment for a prior pregnancy termination? Was there really a vengeful God? Whose fault was it? What did they do wrong? The questions went on and on. I wanted to find some answers.

The Beginning of my Research:

In 1988-9, the last two years of my OB/GYN residency, I began one of my first real research studies into the causes of pregnancy loss. At that time, we thought that about one-half of all pregnancy losses were genetically abnormal. The method used to provide this estimate was flawed requiring the laboratory to grow miscarriage cells. When the pregnancy didn’t grow well inside a perfect womb, the chances for growth in the laboratory were severely hampered. Not only did the cells frequently fail to grow with no answers provided, the most common reported result was 46,XX (normal female). The 46XX result was was reported twice as often as the 46,XY result (normal male). Understanding that there aren’t twice as many girls born as boys, we suspected that the healthier maternal cells, which are always mixed in with the miscarriage cells, overgrew the poorly growing baby’s cells in culture. Since the two different cell lines didn’t come “color coded,” there was no easy way for the laboratory to tell if the results reflected the mother’s cells (often) or the baby’s true chromosome makeup, termed karyotype. Overall, we found the karyotype truly reliable in only 30%+ of the spontaneous loss cases.

My research goal was to examine recurrent miscarriage tissue directly without growing the cells using a device called a flow cytometer. This research took many months to complete but we learned two extraordinary things:

  1. Direct analysis worked well and we were able to identify pregnancies with missing or extra chromosomes using the flow cytometer.
  2. Many of the reported “normal” 46,XX results were actually the mother’s chromosome makeup with the pregnancies themselves found to be severely genetically abnormal.

In reality, we discovered a new method to evaluate miscarriages finding answers where few had previously existed.

Quite unexpectedly, I received an award for the research in my residency and was asked to present my data at the American Fertility Society meeting (now the American Society for Reproductive Medicine) in San Francisco, in 1989, during the first year in my sub-specialty fellowship. It was this research and work performed by many others which helped us to finally understand that 70%+ of all first trimester spontaneous losses were genetically abnormal. Later, during my fellowship, I also complemented my previous work becoming co-author on research examining autoimmune pregnancy loss wherein acquired antibodies attacked the pregnancy resulting in a miscarriage. I was still seeking answers for my patients understanding that we had a very long way to go.

My Motivation: The Parents of the Perfect Imperfect Child

No matter how imperfect the pregnancy was found to be in the laboratory, these were perfect children to the hopeful parents. These innocent and extraordinarily young lives never kept a parent up all night, vomited on their favorite dress or screamed until any sane adult would cry uncle. These pregnancies and children were flawless. They were always beautiful, always bright and always wonderful. These pregnancy losses were perfect beings in the eyes of the parents as they contained every hope and dream they held for their future children. They were potential NFL football players, fishing buddies, best friends and even future Presidents of the United States. They were everything the parents ever dreamed their children might become. It makes perfect sense that they were and, even to this day, often called angels. It was so hard form my patients to loose such a perfect being.

These pregnancy losses were perfect beings in the eyes of the parents as they contained every hope and dream they held for their future children.

In Memory of my Patients and Their Perfect Imperfect Child

We still lose about 25% of all of our pregnancies and it is heartbreaking. While we certainly try their pain, no words seem to do justice for a parent experiencing such grief. For over two decades, though, my practice has been making charitable donations in memory of their pregnancy loss. It was our little way of having something good coming out of such a sorrowful event. While I doubt it made a tremendous difference in the hearts and minds of my patients, I think it gave them some level of comfort. On this 2012 Pregnancy Loss Remembrance Day, I would like to offer a gentle challenge to all of my peers to consider paying it forward by making a similar charitable donation, or performing some other act of kindness, in memory of all of our patient’s pregnancy losses. I believe it would be appreciated by our grieving patients, good for our own souls and would serve the public in a productive and kind manner.

In the Present:

Fast-forward to last year in 2011 where I was involved in a study, now 22 years later following my first flow cytometer study, using newer technology to once again examine the pregnancy tissue directly. This newer technology was called microarray analysis. Using the microarray analysis, we now obtain reliable results 80-90% of the time again providing answers where only guesses existed in the past. I now use the less expensive, rapid and extraordinarily reliable technique on nearly all of our pregnancy losses in the practice. Showing the patients that it wasn’t the food they ate, the swim they took or the short walk they had which caused the miscarriage, but rather, a terrible but uncontrollable flaw in early development of the embryo and fetus, their perfect imperfect child is extraordinarily valuable and does provide some solace.

Sill, We have Only Just Started:

I know we have much more work to do to not only understand why pregnancies are lost but what we can do to change their destiny. Will we someday be able to treat eggs, sperm and early embryos thereby healing the genetic problems before the pregnancy advances to a point of no return? We can only hope for future intervention.

I am fully aware that answering the question of why these perfect imperfect children were lost doesn’t answer all the questions or fully diminish the self-blame that is so commonly felt, but it is a good place to start.

To the memory of all of those we lost and may they keep those of us in the field of reproductive medicine humble and motivated driving us to answer the questions our patients ask of us regarding why they lost their perfect imperfect pregnancies.


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Polycystic Ovarian Syndrome: A Review Written for Patients

How common is polycystic ovarian syndrome?

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases affecting about six percent of reproductive age women. PCOS is one of the main reasons women have difficulty conceiving. About half of all women who do not ovulate on a regular basis will be diagnosed with PCOS.

In recognition of PCOS Awareness Month, I've developed this review for patients dealing with this disease.

How is PCOS diagnosed?

As a syndrome, PCOS is a constellation of findings. Alone, it really is not a disease but simply a label. But physicians use these labels to our patients’ advantage. If we suspect PCOS, we will search for the problems that commonly accompany PCOS, minimizing their effect while possibly changing the course of the illness.

PCOS requires at least two of these three problems for a diagnosis:

  1. Ovulatory dysfunction: irregular cycles or blood progesterone levels that indicate failed ovulation.
  2. Ovarian hyperandroginism: excess male hormones including an unusual amount of facial/body hair or elevated male hormones, such as testosterone, in blood tests.
  3. Polycystic ovaries on transvaginal ultrasound: more than 12 small 3-9mm follicles within each ovary as seen on an ultrasound. At times, we will see the signs of a classic “necklace,” with small cystic follicles located on the periphery of the ovary and which look like a pearl necklace.

Clinically, there seem to be two main types of PCOS: 1) Patients who were essentially born with the problem and have never really had normal cycles, and 2) Patients who have had normal cycles but demonstrate symptoms as they gain weight. Upwards of 80% of all PCOS women are heavy, but 20% can be quite slender.

Other issues include thyroid problems, elevations of the pituitary hormone prolactin and a handful of rare inheritable enzyme deficiencies. These problems need to be screened for and ruled out before settling on the diagnosis of PCOS.

PCOS is probably the single most common diagnosis we see in our patients. Its incidence has been increasing over the last 20 years as the US population has shifted from normal weight to the overweight, obese and morbidly obese categories.

How do you diagnose pre-diabetes in the PCOS patient?

To diagnose insulin and glucose problems, commonly called pre-diabetes, we prefer a 10-12 hour fast with baseline glucose and insulin levels rather than fasting glucose levels alone. The endocrine system is then challenged by having the patient drink 75 grams of glucose (Glucola®), which is called a Glucose Tolerance Test (GTT). Two hours later, insulin and glucose levels are repeated to complete the study. We do not require blood tests every 30 minutes as some protocols suggest, since the fasting and two-hour results are sufficient.

Insulin resistance or actual diabetes is present in nearly half of all PCOS patients. The more the patient weighs, the more likely the diagnosis.

What really causes PCOS?

While many women believe their hormone imbalance is mainly caused by testosterone, insulin seems to be the key hormonal culprit. Excess insulin stimulates the ovaries to produce excess male hormones. Also, excess insulin predisposes the PCOS patient to numerous medial problems, including cholesterol elevation, hypertension and possibly heart disease. Insulin is the key.

How is PCOS best treated?

Treatment in the overweight PCOS patient includes diet, exercise, weight loss and aggressive prevention and treatment of pre-diabetes (insulin resistance and/or glucose intolerance).

Beyond this basic treatment, there are generally two treatment pathways: the “quality of life path” and the “pregnancy path”.

Quality of Life Path

PCOS patients who are not trying to get pregnant should follow the quality of life path and focus on treating the signs and symptoms. Because they don’t shed the inner endometrial lining on a regular basis, PCOS patients are at greater risk for abnormal uterine bleeding, anemia, endometrial polyps, pre-cancer and eventually, even cancer of the lining of the uterus. Hormonal control is used in this pathway. We also suggest aggressive treatment for hair growth, including the use of hormones, electrolysis or laser hair removal. The psychological affects of excess facial and body hair on women should not be minimized and may be the primary concern for PCOS patients.

Pregnancy Path

We recommend that PCOS patients who want to get pregnant use a winning combination of diet, exercise, weight loss and anti-diabetic medications such as metformin (Glucophage®) that are combined with ovulatory medications. Metformin helps in a number of ways including dropping male hormone levels in half and assisting in weight loss. Gas and diarrhea results when too many carbohydrates are consumed while taking metformin, so patients must learn to eat better to avoid the symptoms.

Our practice commonly uses letrazole (Femara®) to stimulate ovulation but sometimes we need to prescribe the old tried and true clomiphene citrate (Clomid®). We occasionally have to suppress the adrenal male hormones through the addition of dexamethasone. We need to be very careful about prescribing injectable follicle stimulating hormone (FSH) medications for PCOS patients since they tend to open the floodgates, resulting in a release of multiple eggs and the potential for a multiple pregnancy. Overstimulation of the ovaries can also lead to significant illness.

Miscarriages seem to occur more often in the PCOS patient. It may have to do with their weight and abnormal insulin levels. While somewhat controversial, even PCOS patients without obvious glucose/insulin problems may benefit from metformin treatment. It must be understood that while these drugs have been extensively studied in the treatment of diabetes, insulin resistance, glucose intolerance and PCOS, the FDA has not granted official approval for the use of these drugs for PCOS.

PCOS patients also more commonly experience gestational diabetes during pregnancy. Weight gain during pregnancy should be held in check as excessive amounts of weight gained can result in insulin dependent diabetes during pregnancy and even afterwards. Pregnancy complications are more common in patients with gestational and insulin dependent diabetes, so an obstetrician will need to carefully monitor a PCOS patient during her pregnancy.

What are long-term concerns for the PCOS patient?

Women with PCOS are at significant risk of developing insulin and non-insulin dependent diabetes mellitus, uterine cancer, elevated lipids, hypertension and cardiovascular disease.

Will a PCOS diagnosis and treatment be covered by insurance?

The coverage of PCOS will depend upon the insurance company. Your physician will try to emphasize the medical diagnoses that are seen with PCOS, such as an ovulatory dysfunction, hirsutism, glucose intolerance or insulin resistance, but coverage cannot be guaranteed. The diagnosis of infertility for the PCOS patient is less often covered but it entirely depends on the particular insurance plan. Medications such as metformin are commonly available free at some pharmacies and supermarkets, so co-pays aren’t even necessary to obtain the medication.

Can PCOS be cured?

In patients that have always had menstrual issues, even when young and slender, an actual cure has not yet been found. However, in the population who became symptomatic after weight gain, diet, exercise, weight loss and medications may actually result in a cure. This “cure” continues as long as the patient’s weight remains close to the level when ovulation and regular cycles returned.

PCOS is a metabolic disease and will require careful control for most patients throughout their lives. That doesn’t mean that the PCOS patient can’t have a family or will always have to suffer the symptoms. Through dedication by the PCOS patient with the assistance of your obstetrician/gynecologist or your friendly neighborhood reproductive endocrinologist, the signs and symptoms of PCOS can certainly be controlled and minimized.

Craig R. Sweet, M.D.
Medical & Practice Director
Reproductive Endocrinologist
Specialists In Reproductive Medicine & Surgery, P.A.

Documents of Interest to the PCOS Patient:

ASRM PATIENT FACT SHEET, Ovarian Drilling for Infertility

ASRM, Hirsutism and Polycystic Ovarian Syndrome, Patient Information Series

ASRM, Patient Fact Sheets, Polycystic Ovarian Syndrome

ASRM, Patient Fact Sheet. Ovarian Drilling for Infertility

PCOS Links of Interest:

The PCOS Challenge: