FORTY IS THE NEW THIRTY, RIGHT? by MARGO R. FLUKER, MD, FRCSC Co-director, Genesis Fertility Centre It s a sign of our times: fit, healthy, fabulous-looking women in their forties and even in their fifties. And some of them are pushing baby strollers. How do they do it? The baby part, I mean. REALITY CHECK The average age of a woman giving birth in Canada is now 30 years, and has been rising steadily for decades. Almost one in five births occur in women 35 years or older. That is nearly four times more frequently than a generation ago. Women today have access to options that their mothers and grandmothers didn t have. We can control our fertility. We have access to effective, reversible forms of birth control. We can delay childbearing to pursue educational and career goals. However, this comes with a price in terms of our fertility. The pronounced age-related decline in fertility means that most women lose their ability to become pregnant in their early to mid-forties. This is often the stage where we start to feel settled financially, socially and emotionally. For many of us, the right time to start focusing on having a family is the same time that our fertility is ending. 8 Creating Families FALL / AUTOMNE 2008
AGE MATTERS As women, we re born with a limited number of eggs, and we spend them. We spend some of them every single month, from the time we re born until the time we go through the menopause, typically in our early fifties. Our ovaries constantly select follicles (the tiny fluid-filled sacs that contain immature eggs) out of the resting stage. In our teens and twenties, a few dozen immature eggs may start to grow each month in order for one to mature and ovulate. In contrast, in our early forties, only a few eggs remain to start growing each month. The eggs that don t ovulate in a given month will disintegrate. This process continues even when we re pregnant or on the birth control pill. It is inevitable and irreversible. Fertility specialists refer to the eggs that remain in our ovaries as our ovarian reserve. The progressive, yearly decrease in the number of eggs is known as the age-related decline in ovarian reserve. Although each woman is slightly different, we can t slow the process down, and there are no medications that will let us put the process on pause to save eggs for later. There are, however, many factors that will speed up ovarian aging, such as: cigarette smoking chemotherapy radiation to the pelvis extensive ovarian surgery family history of early menopause diagnosis of premature ovarian failure (1% of women under 40 years) Most of these are not under our direct control, with one exception cigarette smoking. QUALITY VERSUS QUANTITY The age-related decline in ovarian reserve usually involves a steady decrease in both the number and quality of the eggs that remain in our ovaries. It is estimated that a 38- year-old woman has only 10% of her eggs remaining. From that point onward, the progressive yearly decline in a woman s fertility will start to become one of the biggest factors in her ability to conceive. FALL / AUTOMNE 2008 Creating Families 9
SO, HOW OLD ARE MY EGGS, ANYWAY? The easy answer is that our eggs are as old as we are. No matter how well we ve taken care of ourselves, we never get any younger, and neither do our eggs. However, some women s egg quality or egg quantity declines much earlier than expected. This is a difficult problem to assess because we can t actually see the eggs to evaluate them, except during a cycle of in vitro fertilization (IVF). Figure 1. Pregnancy and Miscarriage vs. Age in Healthy and Fertile Women Once we re in our forties, only a few eggs can start to grow each month. Those remaining eggs are of lower quality than in our teens and twenties. It is harder to get them to ovulate, to fertilize, to implant and to grow normally. This translates into lower pregnancy rates, higher miscarriage rates, and a higher risk of chromosomal abnormalities in the few babies that are born to mothers at this age. Fertility specialists worry about declining ovarian reserve in the following situations: a high FSH level (follicle stimulating hormone) on menstrual cycle day 3 a low antral follicle count on ultrasound (the follicles that have been selected in a given month, see figure 3) low numbers of follicles developing in response to injectable fertility medications IVF cycle that produces few eggs, or low quality eggs or embryos At some point, fertility medications become ineffective, because the ovaries can no longer select more than one egg at a time, or because the quality is too low. TOP TEN MISCONCEPTIONS ABOUT AGE AND INFERTILITY 40 is the new 30. Everyone says I look great for my age. I know lots of women who got pregnant in their 40s. I can t be infertile. I had a baby 5 years ago. I come from a very fertile family. My grandmother had her 9th child when she was 45. I ve been on the birth control pill for years, so I ve been saving my eggs I exercise regularly and I take good care of myself. When I decide to get pregnant, I know it will happen. I had a miscarriage 2 years ago, when I was 43, so I know I can get pregnant. There must be something wrong with my uterus that prevents me from staying pregnant. If did it, so can I. (fill in the name of your favorite 40+ pregnant movie star) I m too young to go through the menopause. Figure 2. Predicted FSH Levels on Menstrual Cycle Day-3 Versus Age Day 3 FSH level. FSH levels rise progressively in the last decade prior to menopause (see Figure 2). Depending on the individual lab and fertility clinic, levels greater than 10-12 IU/L usually indicate decreased ovarian reserve. FSH levels can fluctuate markedly from one month to the next, so one normal level does not guarantee a normal ovarian reserve. In contrast, one abnormal level is usually a sign of decreased ovarian reserve. Once FSH levels are consistently above 12-15 IU/L, the peri-menopausal stage is usually approaching. 10 Creating Families FALL / AUTOMNE 2008
Antral follicle count. This is not a regular pelvic ultrasound from a local ultrasound facility looking for an abnormality in your uterus or ovaries. Instead, it s a vaginal ultrasound done by a fertility specialist. The goal is to count the number of immature (antral) follicles that have been selected out of the resting stage that month. This test helps your fertility specialist predict whether your ovaries will respond to the injectable fertility medications that are used in an IVF cycle. As a rough rule, perhaps half of the antral follicles will grow in response to the injectable medications. However, each mature follicle won t necessarily contain an egg. For example, 10 antral follicles in one ovary might produce five growing follicles, from which four eggs might be available for IVF. WILL USING FERTILITY DRUGS MAKE ME RUN OUT OF EGGS FASTER? Good question. Thankfully, the answer is no. In a normal menstrual cycle, our ovaries pick several eggs out of the resting stage, but only one will be chosen to ovulate. The rest will disintegrate and be reabsorbed. With fertility medications, we try to encourage several of those immature eggs to grow. We re actually making better use of the ones that were recruited, rather than letting so many disintegrate. Figure 3. Antral Follicle Count FALL / AUTOMNE 2008 Creating Families 11
However, the number of eggs recruited will depend on how many remain in the ovaries. The older we are, the lower the number of eggs that can begin growing each month, and the fewer that will respond to fertility medications (see Figure 3). THE GUILT TRIP Why didn t someone tell me? If only I d known Why don t they teach girls about this in high school? Comments like these are heard all too often in an infertility specialist s office. None of us can turn the clock back, but we can be proactive about seeking treatment, and about spreading the message. Each of us can help to raise awareness about age and infertility by talking about it to friends, relatives and co-workers. ADVICE FROM A FERTILITY EXPERT If you re trying to conceive, be proactive. See your family physician or gynecologist to talk about your general health, your risk factors for infertility, and how long you should try before you start to undergo infertility testing. Early testing and/or referral to a fertility specialist may be appropriate if you or your partner have any of the following infertility risk factors: Irregular or absent periods History of IUCD use (especially if it was removed for pain or bleeding) History of endometriosis History of ovarian or tubal surgery, or extensive abdominal/pelvic surgery History of pelvic or genital infection (either partner) History of sexually transmitted disease (either partner) History of prostate infection (male) History of undescended testicles or bilateral hernia repairs in childhood (male) History of vasectomy or tubal ligation 12 Creating Families FALL / AUTOMNE 2008
The easy answer is that our eggs are as old as we are. No matter how well we ve taken care of ourselves, we never get any younger, and neither do our eggs. If you don t have any risk factors for infertility, these are some general guidelines for when to start infertility testing: Women under 35 years: after 12 months of trying Women 35-39 years: after 6-12 months of trying Women over 39 years: after 3-6 months of trying Women or men with a history of infertility risk factors: start testing sooner WHAT CAN TECHNOLOGY DO? Advanced technologies such as IVF are the final treatment option when all other simpler efforts have been unsuccessful. Although complex and expensive, these treatments usually offer the best chance of pregnancy. However, the success of IVF depends on stimulating a woman s ovaries to produce several eggs at a time. From those, a few top quality embryos are chosen to replace in her uterus. Ovarian reserve testing (day 3 FSH and antral follicle count) can help to identify women with reduced ovarian reserve. In such cases, the ovaries are unlikely to produce a reasonable number of eggs, and those women are unlikely to be successful with procedures such as IVF. If you re over 40, or find that you have limited ovarian reserve, ask yourself (and your partner) if you are willing to consider alternatives, such as donor eggs, adoption and child-free living. A FEW GOOD EGGS Egg donation is a variation of IVF for women who have difficulty achieving a healthy pregnancy with their own eggs. You may be a candidate for egg donation if you: have low ovarian reserve have gone through an early menopause have had your ovaries removed have not had good egg or embryo quality during previous IVF attempts FALL / AUTOMNE 2008 Creating Families 13
The woman who donates her eggs must be a healthy young woman (usually under 35 years) who undergoes extensive screening for medical, genetic and infectious disorders. After using injectable fertility medications, several eggs would likely be taken from her ovaries, and then fertilized using your partner s sperm (or a donor sperm sample). To be a recipient of donor eggs, you must have a normal uterus, and be healthy enough to expect that you could safely carry a pregnancy (usually under 51 years). One or two top quality embryos would typically be replaced in your uterus. Depending on the stage and quality of the embryos, most fertility programs anticipate delivery rates of 50% or more in such circumstances. REMEMBER For some women, the diagnosis of decreasing ovarian reserve finally provides some answers for previously unexplained infertility. However, it s also devastating news that often aggravates the sadness and grief they already feel from their struggle with infertility. Feelings of anger, denial, guilt and loneliness are common. Remember that you re not alone in this journey, although it may feel like it sometimes. Infertility affects about one in six couples overall, and at least half of all women over 40 who are trying to conceive. Remember to be proactive about seeking evaluation and treatment, and about spreading the message to others about the effects of age and infertility. Remember that the age-related decline in fertility is the factor that infertility specialists may not be able to overcome. Although it s not easy to move beyond the dream of having your own genetic children, other options are available, including donor eggs, adoption and child-free living. Being infertile doesn t mean that you can t be a parent in some way. Figure 4. Livebirth Rates in IVF Cycles Using a Woman s Own Eggs Versus Donor Eggs (US-IVF Registry, 2005) Lastly, remember to seek support from your partner, your friends and family, the various members of your health care team, the network of professional infertility counselors, and support groups such as IAAC. We are here to help. In Canada, we can only accept altruistic, or volunteer donors. These are friends or family members who are not being paid for their participation, and with whom you are comfortable sharing this experience. Some women find it necessary or preferable to search for an anonymous donor, a woman who is recruited, screened and paid by a fertility clinic, often in the US. This adds to the cost and complexity of the process, but may make egg donation available to women who don t know a suitable volunteer donor. These are not easy choices to make, and not ones to make alone. In addition to your personal support network, the doctors, nurses and counselors at fertility clinics will help you examine these issues. About the author Dr. Margo Fluker is the co-founder and co-director of Genesis Fertility Centre in Vancouver. She has published dozens of research papers, textbook chapters and national guidelines in the areas of reproductive endocrinology and infertility, premature ovarian failure, and age-related infertility. While nurturing Genesis through its growth into one of Canada s largest and most successful IVF programs, she has also taken responsibility for the Centre s donor egg program. She is passionate about her work at the clinic, adventure travel, and any activities that take her outdoors. FALL / AUTOMNE 2008 Creating Families 15