PCOS and Cardiovascular Risks

Women with Polycystic Ovarian Syndrome (PCOS) have an increased risk for heart disease and possibly heart attacks compared to other women of the same age and weight, studies show. Specifically, the indications of cardiovascular disease include sub-clinical hardening of the arteries and signs of significant vascular impairment, including irregularities of the cells lining the arteries and blood vessels and increased thickness and decreased compliance of arterial walls. While the main focus of PCOS specialists is treating infertility, menstrual irregularities and unwanted hair, it’s important for women and their physicians to pay attention to the increased cardiovascular risk that accompanies PCOS as well, said Dr. Pinar Kodaman, a reproductive endocrine specialist who focuses on reducing cardiovascular risks for PCOS patients through lifestyle modification and medication. Dr. Kodaman is part of the multidisciplinary team at the Yale Polycystic Ovarian Syndrome Program that treats all aspects of PCOS.

Cardiovascular disease remains the most common cause of death among women, and risk of death from a heart attack increases with age, especially in the United States where there is a high incidence of obesity, a key contributor to heart disease.

At least 50% of women with PCOS in the U.S. are obese, 40% are insulin resistant, and 10% have type II diabetes. Insulin resistance, coupled with the body’s tendency to compensate by producing even more insulin, is one of the major factors in the development of Metabolic Syndrome, and this condition exacerbates elevated lipids in the blood, obesity, glucose intolerance and unwanted facial and body hair among women with PCOS.

PCOS is also associated with increased oxidative stress, high blood pressure, elevated levels of homocysteine, an amino acid in the blood that is an indicator of higher risk of heart disease, and dyslipidemia (an imbalance of lipids in the blood), all of which also contribute to cardiovascular risk. Interestingly, even young and lean women with PCOS tend to have unfavorable cardiovascular risk profiles, Dr. Kodaman said.

The studies on cardiovascular illness and death among PCOS patients are limited; however, the cardiovascular risks associated with the syndrome are clear.

The medical management of PCOS includes therapy for failure to ovulate or irregular ovulation, unwanted body and facial hair, as well as treatment of endometrial hyperplasia, a condition in which the lining of the uterus grows too much. In addition, obesity, dyslipidemia, hypertension, and insulin resistance should also be addressed if present. Lifestyle modification with diet and exercise are first line treatments, followed by insulin sensitizers, such as metformin, for insulin resistance and statin drugs, like Lipitor, for dyslipidemia. Statins may have additional beneficial roles in decreasing oxidative stress and improving hyperandrogenemia and other biochemical disorders of PCOS.

PCOS is the most common endocrine disease affecting women of reproductive age. Up to 10 million women in the United States have PCOS, a condition characterized by hyperandrogenism (excessive secretion of male sex hormones that results in unwanted facial and body hair) and oligomenorrhea (irregular menstrual periods). Frequently, the ovaries also have a polycystic appearance on ultrasound, which appears as multiple small follicles around the perimeter of the ovary. The cause of PCOS is unknown and researchers are actively investigating it.

PCOS occurs shortly after puberty and consists of altered gonadotropin secretion favoring luteinizing hormone production, which stimulates the ovaries to produce increased levels of androgens (male sex hormones). In addition, at the level of the ovary, the follicles make less estrogen and luteinize prematurely, thereby failing to ovulate.

While PCOS is an endocrine disorder affecting women during their reproductive years, its consequences continue to have detrimental effects in the postmenopausal years. A recent a study found that postmenopausal women with clinical features of PCOS had a greater incidence of cardiovascular events. Therefore, it is imperative that PCOS be diagnosed in a timely fashion and treated effectively across the lifespan.

PCOS and Nutrition

While the causes of PCOS remain unclear, most experts believe insulin plays a major role in its development. The majority of PCOS patients have decreased insulin insensitivity, causing high levels of insulin or what is commonly known as insulin resistance. Approximately 50% of women affected by PCOS are overweight.

Risk Factors
Insulin resistance places an individual at increased risk for:
• Abnormal carbohydrate metabolism – raising the likelihood of developing type II diabetes
• Heart disease due to:
– Increased levels of LDL or “bad” cholesterol
– Decreased levels of HDL or “good” cholesterol
– Increased levels of triglycerides
– Increased blood pressure
• Significant weight gain and difficulty losing weight
• Low self-esteem

Lifestyle Modifications

Diet
Diet and exercise have been established as the first line of defense against PCOS. Studies show that a 5%-10% weight loss may substantially improve the metabolic and reproductive abnormalities associated with PCOS while lowering the risk of heart disease and type II diabetes. A registered dietitian (RD) can help customize a balanced diet, low in fat and moderate in carbohydrates, to help you achieve and maintain your weight loss goals. The RD will evaluate your current diet, lifestyle and risk factors and
establish a nutrition plan specific to your individual needs.
The following factors will be considered:
• Current height and weight
• Ideal body weight (IBW)
• Age, overall health and medical history
• Current medications or supplements taken
• Current eating patterns, food preferences and dietary customs

Exercise
Evidence clearly supports the importance of physical activity for women affected by PCOS; exercise may be just as important as diet in treating the disorder. Both aerobic exercise and strength conditioning can be effective in:
• Improving lipid levels
• Improving insulin insensitivity
• Lowering blood pressure
• Improving self-esteem
• Managing weight
• Aiding in prevention and treatment of chronic disease

An RD can help develop a customized exercise plan based on your preferences and lifestyle pattern.

Pregnant with PCOS

Pregnant women with PCOS face a number of challenges before, during and after their pregnancies. To address these concerns, Yale’s infertility specialists and Maternal-Fetal Medicine specialists at the Yale PCOS Program provide on-site consultations prior to conception and throughout pregnancy for women likely at high risk for pregnancy-related complications.

Pregnancy Risks
• Infertility – Due to ovulation disturbances, women with PCOS may find it difficult to get pregnant. YFC boasts one of the highest success rates in the region for managing PCOS-related infertility, offering individualized management strategies to minimize the risks of ovarian hyperstimulation and multiple pregnancy while maximizing success of fertility treatments. Fertility therapies include ovulation induction strategies, injectable hormones, aromatase inhibitors and in vitro fertilization.

We also recommend lifestyle interventions that may help with spontaneous ovulation.
• Miscarriage – Women with PCOS may be at increased risk for spontaneous miscarriage. Contributing factors include elevated insulin levels (insulin resistance) and high levels of luteinizing hormone (LH) or androgens (male hormones). Miscarriage risk can be reduced by lowering insulin levels through weight loss or with insulin-lowering medicines such as Metformin. Women with elevated homocysteine levels may also require increased folic acid.
• Pregnancy Complications – Women with PCOS are particularly at risk for gestational diabetes, which may increase the risk of birth defects, miscarriage, preeclampsia, preterm delivery, macrosomia (excessive birth weight) and birth injury. Weight reduction and lowering insulin levels before pregnancy are beneficial to ensuring a healthy pregnancy.
• Multiple Pregnancy – Pregnancy with more than one fetus increases the overall risk for pregnancy-related complications in women with PCOS. Because they are at high risk for multiple pregnancy following fertility treatment compared to women with other causes for infertility, our goal is to minimize this risk by utilizing gentler treatment protocols that reduce the likelihood of multiple gestation.
In addition to working with high-risk pregnant women with PCOS, YFC monitors all PCOS pregnancy outcomes to help the medical community understand the fetal and perinatal implications of PCOS.

Risks to Children of Women with PCOS
Studies suggest that PCOS diagnosis may have implications for the children of women with PCOS.
• Daughters of women with PCOS may grow up to exhibit the characteristic features of PCOS.
• Weight problems, insulin resistance and high cholesterol are consistently seen in children of women with PCOS.

Healthy lifestyle and healthy weight goals are therefore important not just for women with PCOS, but also for their children.

Infertility and PCOS

Ovulation disturbance is the most likely cause of infertility in women with PCOS who do not ovulate regularly, although other factors may contribute to fertility problems in some couples. The Yale PCOS Program provides state-of-the-art management of PCOS-related infertility. With one of the highest success rates in the region, our experts offer individualized management strategies to maximize success while minimizing the risks of ovarian hyperstimulation and multiple pregnancy in patients with PCOS.

Treatment begins with a basic infertility workup:
• Pelvic ultrasound
• Prenatal lab tests
• HSG (hysterosalpingogram) – X-ray of the uterus and fallopian tubes
• SHG (sonohysterogram) – saline ultrasound to determine uterine abnormalities
• Semen analysis
• Complete health assessment, including a risk profile for diabetes, heart disease and other diseases associated with PCOS
After reviewing these test results, we meet with
you to determine the best course of action.

Options include:
• Ovulation induction – A number of medications are available to induce ovulation in women with PCOS; dose and treatment duration are individualized:
– Clomid – orally administered fertility medication
– Gonadotropins – injectable fertility medications for those who do not respond to simpler treatments; more expensive with greater chance of multiple pregnancy
– Aromatase inhibitors – trigger ovulation in women; safer and less expensive than some alternatives
• Insulin sensitizing agents – Metformin has been shown to restore normal ovulation in some women with PCOS, may improve response to other fertility drugs, and has little or no risk of multiple pregnancies.
• In vitro fertilization (IVF) – removing eggs from your body, fertilizing them with your partner’s sperm, and implanting a fertilized egg into your womb. We utilize minimal stimulation and blastocyst culture and transfer strategies to reduce risks for such problems as ovarian hyperstimulation syndrome and multiple pregnancy.
• Lifestyle modifications – Because being overweight or obese may reduce a woman’s fertility, weight loss is highly recommended to improve fertility and pregnancy outcome. We provide a comprehensive lifestyle management program that includes weight management counseling.
• Optimizing Vitamin D status – Our ongoing research indicates lower pregnancy rates following IVF in women with low blood levels of Vitamin D. Vitamin D levels are assessed for all women attending the Yale PCOS Program and treatment provided to achieve normal levels.

Health Risks of PCOS

Women with PCOS are at increased risk fordeveloping a number of long-term health problems. At the Yale PCOS Program, we seek to address these risks before they become serious medical issues, with a combination of lifestyle modifications and medical interventions.
• Endometrial Hyperplasia – A thickening of the endometrium (uterine lining) can cause heavy or irregular bleeding, and may lead to pre-cancerous changes in the endometrium that could develop into endometrial cancer.
• Cardiovascular Disease Risk – Women with PCOS have a greater chance of developing Metabolic Syndrome – a cluster of risk factors that raise the likelihood of a heart attack or stroke later in life.
These factors include:
• Obesity – approximately 50% of women with PCOS in the US are obese
• Dyslipidemia – increased total cholesterol, triglycerides or both and decreased HDL (good cholesterol)
• Elevated blood pressure (hypertension)
• Insulin resistance – 40% of women with PCOS are insulin resistant
• Type II diabetes – affects 10% of women with PCOS
• Sleep apnea – can present as disturbed sleep, frequent sleep interruptions, restlessness, snoring, and daytime fatigue and sleepiness

Given these risk factors, women with PCOS have a seven-fold increased risk for heart attack and are four times more likely to have a stroke compared to women without PCOS.
• Breast Cancer – Some studies indicate that there is a correlation between PCOS and breast cancer, but the evidence so far is inconclusive.

Women with PCOS are encouraged to visit the Yale PCOS Program for a complete metabolic assessment and risk profile. Your initial examination will include a complete medical history, physical exam with BMI measurement, pelvic ultrasound and all appropriate lab tests. Once we have assessed your risk, we will tailor an individualized plan to meet your specific needs.

Cosmetic Concerns and Symptoms of PCOS

Cosmetic concerns are common in women with PCOS. While not hazardous to health, they may be a source of significant psychological distress. The Yale PCOS Program helps women manage bothersome cosmetic concerns with medical interventions, lifestyle modifications, and psychological support and counseling.

Hirsutism
Hirsutism is the excess growth of coarse, visible body hair, which can be evident on the upper lip, around the jaw, on the cheeks, and sometimes on the chest, stomach and upper thighs. Increased male hormone levels and insulin contribute to hirsutism in women with PCOS. Treatments include:
• Anti-androgens* (Flutamide, Finasteride and Spironolactone) – to decrease the male hormone’s effect on hair growth
• Vaniqa (Eflornithine) cream – to reduce facial hair
• Birth control pills* – to decrease production of male hormones
• Non-pharmacological options – such as shaving, bleaching, waxing, electrolysis and laser hair removal

Acne
Acne is common in women with PCOS and is caused by elevated male hormone and insulin levels. Treatments include:
• Anti-androgens* – to counter the effects of the male hormone on skin
• Benzoyl peroxide – a common over-the-counter ingredient used in creams and lotions to treat mild to moderate acne
• Topical retinoids* – prescription creams formed from Vitamin A that help unclog pores and increase cell turnover
• Topical antibiotics – creams, lotions or gel pads that reduce inflammation by killing bacteria

Hyperpigmentation
Hyperpigmentation (Acanthosis nigricans) causes thickened, darkened skin patches that commonly affect the nape of the neck, armpits, skin under the breasts, and the groin. Insulin resistance causes this condition, which improves with adequate treatment of the underlying endocrine disorder. Treatment may include:
• Weight loss
• Dietary/pharmaceutical control of insulin resistance (such as Metformin)
• Topical exfoliants (e.g., lactic acid, tretinoin, urea-based medications)

Hair loss
Hair Loss (Androgenic alopecia) in women with PCOS is commonly due to a male hormone imbalance.
Treatments include:
• Minoxidil (Rogaine) – the only FDA-approved treatment for female pattern baldness, used topically on the scalp
• Anti-androgens* (Finasteride) – to counter the effects of the male hormone on hair loss

Excessive body weight
Approximately 50% of women with PCOS are overweight, due to an imbalance in caloric intake and caloric expenditure.
Management options include:
• Nutritional counseling – Individualized nutritional plans are created based on the patient’s preferences to ensure long-term compliance
• Physical activity counseling – Detailed assessment of patient’s lifestyle and individualized counseling to achieve optimal caloric expenditure
• Therapy – For certain patients, medical and/or surgical weight loss (bariatric surgery) and psychological counseling may be considered; treatment plans are individualized
* For women who are not pregnant and are not trying to get pregnant

Weight problems, cosmetic concerns, and distress regarding body image and infertility can be a source of tremendous stress for women with PCOS. Studies have identified that women with PCOS may be more likely to suffer from anxiety and depression. Chronic stress itself may contribute to some of the symptoms of PCOS (such as irregular menses) and be detrimental to fertility success. In recognition of the importance of the emotional component of PCOS, the Yale PCOS Program offers psychological support and counseling to complement medical, nutritional and lifestyle management strategies, and to help improve overall well-being in women of all ages diagnosed with PCOS. Psychological counseling options are available on site with our experienced counselor to help patients cope with:
• Menstrual irregularities
• Concerns related to self-image resulting from weight-related problems, acne, excessive body hair or hair loss
• PCOS-related infertility

Adolescents with PCOS may be especially prone to psychological and emotional distress from symptoms of PCOS. We offer a comprehensive program of psychological counseling and support for adolescents and their families to help cope with a PCOS diagnosis.

Signs and symptoms of polycystic ovarian syndrome (PCOS) can often be seen as a girl progresses through puberty. Although irregular menstrual cycles are part of the normal course of puberty, girls with PCOS are more likely to exhibit exaggerated symptoms such as:

• Irregular menstrual cycles for longer than a year
• Increased androgen production resulting in unwanted hair growth or scalp hair loss
• Increased body mass and insulin resistance
• Delay of more than two years between onset of puberty and occurrence of menses
• Early appearance of pubic hair prior to puberty
• Heavy uterine bleeding
• Acne
• Depression
• Weight gain

At the Yale PCOS Program, our medical practitioners include Ob/Gyns specializing in adolescent medicine. During a young woman’s first appointment, we strive to establish a physician/patient relationship that ensures the patient’s and family’s comfort and confidence in discussing any health issues and concerns. Discussions are individualized to the adolescent’s needs and include a review of:

• Normal pubertal development and menstruation
• Healthy eating habits and body image
• Preventive healthcare including the HPV vaccine and reproductive hygiene (including pregnancy and sexually transmitted infection prevention, if appropriate)
• PCOS-related concerns

Assessment of PCOS-related symptoms consists of a thorough medical evaluation, including a detailed medical history, nutritional assessment, physical examination, laboratory testing and an abdominal ultrasound (if appropriate). Treatment is individualized to the needs of each adolescent and tailored to her life stage. Similar to adult women, therapies for adolescents with PCOS include:

• Lifestyle modifications including diet and exercise to lessen the
symptoms of PCOS by improving insulin insensitivity and lipid levels, managing weight, and increasing self-esteem
• Birth control pills to regulate menstrual cycles and reduce androgen levels, which improves acne and excessive body hair, and may have a beneficial effect on overall body image
• Insulin sensitizing agents such as Metformin to lower insulin levels and improve metabolic problems associated with PCOS
• Anti-androgen treatments to decrease unwanted hair growth
when non-medical treatments are ineffective
• Psychological support for adolescents and families to help cope

What is Endometriosis?

The name comes from the word "endometrium," which is the tissue that lines the uterus. During a woman's regular menstrual cycle, this tissue builds up and is shed if she does not become pregnant. Women with endometriosis develop tissue that looks and acts like endometrial tissue outside the uterus, usually on other reproductive organs inside the pelvis or in the abdominal cavity. Each month, this misplaced tissue responds to the hormonal changes of the menstrual cycle by building up and breaking down just as the endometrium does, resulting in internal bleeding.

Unlike menstrual fluid from the uterus which is shed by the body, blood from the misplaced tissue has nowhere to go, resulting in the tissues surrounding the endometriosis becoming inflamed or swollen. This process can produce scar tissue around the area which may develop into lesions or growths. In some cases, particularly when an ovary is involved, the blood can become embedded in the tissue where it is located, forming blood blisters that may become surrounded by a fibrous cyst.

A staging system has been developed by the American Society of Reproductive Medicine (formerly the American Fertility Society). The stages are classified according to the following:
Stage Level of Severity
Stage I minimal
Stage II mild
Stage III moderate
Stage IV severe

The stage of endometriosis is based on the location, amount, depth, and size of the endometrial implants. Specific criteria include:

* the extent of the spread of the implants
* the involvement of pelvic structures in the disease
* the extent of pelvic adhesions
* the blockage of the fallopian tubes

The stage of the endometriosis does not necessarily reflect the level of pain experienced, risk of infertility, or symptoms present. For example, it is possible for a woman in Stage I to be in tremendous pain, while a woman in Stage IV may be asymptomatic. In addition, women who receive treatment during the first two stages of the disease have the greatest chance of regaining their ability to become pregnant following treatment.

The causes of endometriosis are still unknown, although many theories abound. One theory suggests that during menstruation some of the tissue backs up through the fallopian tubes into the abdomen, a sort of "reverse menstruation", where it attaches and grows. Another theory states that certain families may have predisposing genetic factors to the disease. Current research is also looking at the role of the immune system in activating cells that may secrete factors which stimulate endometriosis.

How is endometriosis diagnosed?

For many women, simply having a diagnosis of endometriosis brings relief. Diagnosis begins with a gynecologist evaluating a patient's medical history and a complete physical examination including a pelvic exam. A diagnosis of endometriosis can only be certain when the physician performs a laparoscopy (a minor surgical procedure in which a laparoscope, a thin tube with a lens and a light, is inserted into an incision in the abdominal wall. Using the laparoscope to see into the pelvic area, the physician can often determine the locations, extent, and size of the endometrial growths.).

Other examinations which may be used in the diagnosis of endometriosis include:

Biopsy- a procedure in which tissue samples are removed (with a needle or during surgery) from the body (often during a laparoscopy) for examination under a microscope; to determine if cancer or other abnormal cells are present.

Ultrasound- a diagnostic imaging technique which uses high-frequency sound waves to create an image of the internal organs.

Computed tomography (CT or CAT scan)- a non-invasive procedure that takes cross-sectional images of internal organs; to detect any abnormalities that may not show up on an ordinary x-ray.

Magnetic resonance imaging (MRI)- a non-invasive procedure that produces a two-dimensional view of an internal organ or structure.

What can be done to ease the pain of endometriosis?

Simple tips that can help ease the pain of endometriosis include rest, relaxation, and meditation; warm baths; prevent constipation; regular exercise; use of hot water bottle or heating pad on your abdomen.

Treatment for endometriosis

Specific treatment for endometriosis will be determined by your physician based on:

- Your overall health and medical history
- Current symptoms
- Extent of the disease
- Your tolerance for specific medications, procedures, or therapies
- Expectations for the course of the disease
- Your opinion or preference
- Your desire for pregnancy

In general, treatment for endometriosis may include

- "Watchful waiting" - to observe the course of the disease
- Pain medication - such as ibuprofen or other over-the-counter analgesics
- Hormone therapy, including:
- Gonadotropin-releasing hormone agonist (GnRH agonist), which stops ovarian hormone production, creating a sort of "medical menopause"
- Danazol, a synthetic derivative of testosterone (a male hormone)
- Oral contraceptives, with combined estrogen and progestin (a synthetic form of progesterone) hormones, prevent ovulation and reduce menstrual flow
- Progesterone alone

Surgical techniques which may be used to treat endometriosis include:

Laparoscopy- (also used to help diagnose endometriosis) a minor surgical procedure in which a laparoscope, a thin tube with a lens and a light, is inserted into an incision in the abdominal wall. Using the laparoscope to see into the pelvic area, the physician can often remove the endometrial growths.

Aparotomy- a more extensive surgery to remove as much of the displaced endometrium as possible without damaging healthy tissue.

Hysterectomy- surgery to remove the uterus and possibly the ovaries.

Sometimes a combination of therapies are used, such as conservative surgery (laparoscopy or laparotomy), along with hormone therapy.

Some women also benefit from alternative treatments used in conjunction with other medical and surgical therapies for the treatment of endometriosis.

These include:

- Traditional Chinese medicine
- Nutritional approaches
- Homeopathy
- Allergy management
- Immune therapy

It is important to discuss any/all of these treatments thoroughly with your physician, as some may conflict with the effectiveness of others.

Where are endometrial implants often found?

Endometriosis is most often found in the ovaries, but can also be found in other places (indicated above in purple), including:

- The fallopian tubes
- Ligaments that support the uterus
- The internal area between the vagina and rectum
- Outer surface of the uterus
- In the lining of the pelvic cavity

Occasionally, the implants are found in other places, such as:

- Intestines
- Rectum
- Bladder
- Vagina
- Cervix
- Vulva
- Abdominal surgery scars

While any woman may develop endometriosis, the following women seem to be at an increased risk for the disease:

- Women who have first-degree relative (mother, sister, daughter) with the disease
- Women who are giving birth for the first time after age 30
- Caucasian women
- Women with an abnormal uterus

The following are the most common symptoms for endometriosis, however, each individual may experience symptoms differently.

Symptoms of endometriosis may include:

- Pain, especially excessive menstrual cramps which may be felt in the abdomen or lower back
- Pain during intercourse
- Abnormal or heavy menstrual flow
- Infertility
- Fatigue
- Painful urination during menstrual periods
- Painful bowel movements during menstrual periods
- Other gastrointestinal problems (i.e., diarrhea, constipation, and/or nausea)

It is important to note that the amount of pain a woman experiences is not necessarily related to the severity of the disease - some women with severe endometriosis may experience no pain, while others with a milder form of the disease may have severe pain or other symptoms

The Egg Donation Process

Once a woman has been accepted as an egg donor, she will take a series of fertility drugs (some of which must be injected) to stimulate her ovaries to produce many eggs at one time. While using the drugs, she will be scheduled for several medical tests (blood tests and ultrasounds), and after her eggs have matured they will be removed using a needle and ultrasound probe. The eggs will be fertilized with sperm from the intended father or a sperm donor in our state of the art embryology laboratory and will incubate for two to five days. A number of the fertilized embryos will then be transferred to the recipient’s uterus and a pregnancy test will be performed 9 to 12 days after the transfer.

Becoming an Egg Donor

Becoming an egg donor means that you are giving another woman the opportunity to achieve pregnancy, experience childbirth, and realize her dream of building a family. Egg donation can be the answer for women who have unsuccessfully tried other infertility procedures or for women who were born without ovaries, whose ovaries have been removed, or whose ovaries may have been may have been damaged by radiation or chemotherapy.

Donors may be anonymous or they may be known. Anonymous donors are recruited from local communities, are carefully screened, and their identities remain anonymous throughout the entire donor process. Known donors may be a family member, relative, or friend of the recipient.

Making the Right Choices When it Comes to Multiples

Fertility experts walk a fine line between dream fulfillment and medical failure as they try to help their patients become pregnant while avoiding high-order multiple births.

The recent birth of octuplets to a California woman receiving infertility treatment has raised questions about the practices used by infertility doctors. Dr. Pasquale Patrizio, director of the Yale Fertility Center, discusses the safeguards in place to ensure that nothing similar happens here.

Q. What is your reaction when you hear a story like the one about the woman in California giving birth to octuplets?

A. I am not happy. High order multiple births (triplets or more) resulting from in vitro fertilization (IVF) are considered medical failures. Besides the known pregnancy complications of multiple births—preterm labor and the many health concerns related to premature delivery—there is also the issue of how are you going to raise these children. If someone comes to me and already has six children, like in this particular case, I have a duty to refer this patient to social service. If she’s asking me to transfer eight embryos, something is not right.

Q. IVF treatments can cost $10,000 a piece. What do you do if a patient comes to you and says, “I don’t’ have a lot of money for IVF treatments. Could you please implant as many embryos as possible to improve my chances of getting pregnant on the first try?”

A. We have to follow the guidelines developed by the American Society of Reproductive Medicine. It’s simply not okay to transfer six or seven embryos into a woman who is younger than 35 and has a good prognosis for a successful pregnancy. So, it doesn’t matter if the woman requests that I implant all the embryos. I’m not going to honor that request.

Q. What are the guidelines?

A. For a woman younger than 35 with a good prognosis, the guidelines say one embryo if the transfer is performed on day five after egg retrieval, with a maximum of two if the transfer is performed on day three. The older the woman, the more embryos we’re allowed to transfer. At 40, you can transfer three or four tops. For patients 42 or older, you can transfer up to 5. If someone goes beyond this, you really need a valid justification, and it’s very, very rare.

Q. But these are just guidelines, right? They’re not mandatory?

A. Right. We voluntarily file annual clinic summary reports with the Society of Assisted Reproductive Technologies (SART). The reporting rate is about 95 percent, so we’re doing a pretty good job of making our data available for public scrutiny and information.

Q. What do you report?

A. The age of the woman, the number of cycles started, the number of retrievals, the average number of embryos transferred by age group, the number of pregnancies, the number of deliveries, the number of multiple births and the number canceled cycles. Centers can also be audited, which is one way we protect citizens from cheaters. If a center makes up numbers and is caught, there can be sanctions.

Q. Would there be less pressure from patients to implant multiple embryos if insurance for infertility treatment were better?

A. It’s possible. In Belgium and some other European countries, insurance pays for treatment, and insurers tell you how many embryos you can implant. In the United States only 15 out of the 50 states [including Connecticut] mandate insurance coverage for infertility. Somebody should do a study on whether states that cover infertility have fewer multiple births than states that don’t.

Q. Does competition among centers add to the temptation to implant more embryos to keep the pregnancy success rate high?

A. There’s definitely pressure on centers to compete, and patients do their homework about clinic success rates. There are 425 fertility clinics in the United States, but the number of cycles of IVF has flattened, because the baby boomer generation is now older.

Q. Is the number of high order multiple births going down?

A. The number is indeed going down. The number of triplets is now around 2 percent. A few years ago it was 3.5 to 4 percent, and in 1996 it was 7 percent. The average number of embryo transfers has been decreasing, too, from an average of four in 1996 to 2.6 now.

Q. What about selective reduction (targeting one or more fetuses in a multifetal pregnancy for termination) as a way of avoiding multiple births?

A. We try not to go there, but since women are very well-informed about infertility treatments and procedures, sometimes they ask you, “Please implant three embryos. If they all survive, I’ll have a selective reduction.” I’m personally not very comfortable with this concept. I only want to use it as a last, last, last resort.

Q. Does an incident like the California octuplets undermine the credibility of your field?

A. Yes, of course. You see how much ink has been spent on this issue, and it makes us, as a professional group, look bad. There is so much hard work by a team of professionals behind the scenes to help couples achieve what is perhaps one of the most important reasons we are on the planet: to reproduce, to have offspring.

Q. With all that has been written about the octuplet case, has anything been lost in the debate?

A. What has been lost is the sacrifice, the hours and hours of work that have gone into creating a treatment for infertility that is successful and the incredible amount of joy we have been able to bring to families.

Q. Besides implanting more embryos, what else can be done to improve an infertile couple’s odds of having a baby?

A. Research is being done on identifying the best embryo to implant, trying to find markers of embryo implantation potential. We’re also looking at methods for identifying the best egg.

Q. How is that research going?

A. I predict that five years from now you’ll see many more single-embryo transfers. There has to be a coalition of events: technological advances, better insurance coverage, less competition among clinics, but I am convinced that in a few years, this is going to happen, and higher order pregnancies from IVF will be history.

—Jennifer Kaylin

Photo by Jennifer Kaylin

To find out more about the Society for Assisted Reproductive Technology or to view clinical survey reports from any center in the United States, go to www.sart.org.