FERTILITY AND AGE. Introduction. Fertility in the later 30's and 40's. Am I fertile?

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1 FERTILITY AND AGE Introduction Delaying pregnancy is a common choice for women in today's society. The number of women in their late 30s and 40s attempting pregnancy and having babies has increased in recent years. At least 20 percent of women wait to begin their families until after age 35. This is due to a number of factors, such as delaying childbirth until careers are established, waiting for a stable relationship, wanting to achieve financial security or being unsure about the desire for parenthood. However, it is important that women and their partners take account of the facts that age may affect their ability to conceive and to successfully continue a healthy pregnancy. It is also important to be aware of the possible tests and treatments that may be offered to older women to assist them in achieving pregnancy. This information sheet addresses the realities and challenges a woman may face when considering pregnancy after the age of 35. All men and women come to reproductive age with a background of being infertile, hypo-fertile, normally fertile, hyper-fertile or super-fertile. The only way of knowing what category you may fall into is often only discovered late, when child bearing is delayed. Fertility in the later 30's and 40's It is a biological fact that there is a decrease in fertility with advancing age. It is estimated that the chance of becoming pregnant in any one month is about 20 percent in women less than 30 years of age, but only 5 percent in women more than 40. Even with advanced infertility treatments, such as in vitro fertilisation (IVF), fertility decreases and the chance of miscarriage increases in women after age 40. There are several explanations for this and they include such medical conditions as high blood pressure or diabetes, changes in ovarian function and alterations in the chromosome makeup of eggs released by the ovaries. By the time a woman is 35 or 40, she has also had more time to develop such gynaecological disorders as endometriosis that decrease fertility in ways that are not completely proven. Fertility by implication, may provide good probability of success in IVF, such as if a woman s tubes have been clamped and she meets a new partner. Ageing doesn't just affect women. Though perhaps not as abrupt or noticeable as menopause is for women, changes in fertility and sexual functioning do occur in men as they age. First, the ability to conceive decreases with increasing age. The testes tend to get slightly smaller and softer with age. Semen quality and sperm morphology (shape) and motility (movement) all tend to decline. Overall it is estimated that male fertility declines about 30% between the ages of 30 to 50 years. Despite these changes, there is no maximum age at which men are not capable of conceiving a child, as evidenced by occasions when men in their 60s and 70s conceive with younger partners. Sexual functioning in men may also change with ageing. Often there is a slight decrease in a man's testosterone level that can cause a decrease in libido (sexual drive). Men may have difficulty achieving and/or maintaining erections as they age. Illness, stress or reactions to medications, all of which tend to occur more frequently as men get older, can accelerate these changes in testosterone, libido and sexual functioning. Am I fertile? Unfortunately, there is no simple way of telling whether a woman or a couple will have difficulty in conceiving. Tests, such as a semen analysis for the man and a hysterosalpingogram (HSG) or laparoscopy for the woman, may diagnose some of the conditions that impair fertility but, when there are only mild disorders present, it is often not possible to predict their effect on the monthly chance of pregnancy. 1

2 Although most infertility specialists recommend at least one year of attempting to conceive before undergoing tests, older couples may be offered evaluation after as little as six months. Ovarian changes In order to understand the effect of age on the ovary it is necessary to examine the monthly process by which ovulation (egg release) occurs. The hypothalamus and pituitary gland, located in the brain, orchestrate the events leading to ovulation and regular menstruation. The hypothalamus stimulates the pituitary to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). These hormones are secreted into the bloodstream and control the growth of eggs (oocytes) and the production of the female hormones, oestradiol and progesterone by the ovaries. Most women have about 300,000 eggs in their ovaries at puberty. For each egg that matures and is released (ovulated) during a menstrual cycle, at least 500 to 1000 do not fully mature and are reabsorbed by the body. By the time a woman reaches menopause, which usually occurs between the age of 40 and 56 years, there are only several thousand eggs remaining. These remaining eggs generally do not respond well to the secretion of FSH and LH signals from the pituitary gland and the level of these hormones in the bloodstream increases in an attempt to stimulate the ovaries. An elevated blood FSH level early in the menstrual cycle (Day 2-5) suggests that the ovary is not responding normally to the signals from the pituitary. This lack of ovarian responsiveness is indirect evidence of poor egg quality. The decrease in the ovary's response to FSH and LH from the pituitary gland results in a lowering of oestrogen and progesterone produced by the ovary. The menstrual cycle may first become shorter but, owing to the complex processes by which menstruation occurs, longer cycles and heavier bleeding may also occur. Because oestrogen and progesterone are critical for the normal development of the lining of the uterus (endometrium) where the early embryo must attach and grow, any reduction in these hormones with age will decrease the chance of pregnancy. While it is sometimes possible to correct such alterations with the use of fertility drugs this is by no means always so. Fertility drugs, such as clomiphene, stimulate the pituitary to release more FSH and will not be effective if the ovaries are becoming unresponsive to this hormone. Changes in Eggs and Sperm Whereas new sperm are generated daily from stem cells (or parent cells) in the testis, all women are born with a fixed number of eggs which are held in a state of arrested maturation until the hours before each ovulation. The final stage of maturation involves a division and a halving of the chromosome number and this step is increasingly prone to error as the woman ages. The result is a greater risk of a chromosomal abnormality that, in turn, results in a greater risk of a miscarriage because this is the most common reason for this form of pregnancy loss. The great majority of abnormal conceptions are recognised by nature and miscarried, usually before the 12th week of pregnancy. It has been recognised for some time that a woman s chance of a miscarriage increases with age as shown in Table 1. However, these errors in chromosome number also result in a greater risk of Down s syndrome and this also has a direct relation to maternal age as shown in Table 2. The source of the decreased pregnancy rates in older women is thought to be due, in large part, to the increase in the number of eggs with chromosomal problems. When donor eggs are collected from women in their 20s and 30s, fertilised and placed in the uterus of a woman more than 40, then the rate of pregnancy in the older woman is much higher than she could expect if she had used her own eggs. The success of this egg donation confirms that egg quality is the primary barrier to pregnancy in older women. Unfortunately, there is nothing that a woman can do to prevent the age-related decline in egg quality. Although age is not an absolute barrier to pregnancy, any infertility treatment, with the exception of the use of donor eggs, will be less successful in women more than 38. Paternal age has much less of an effect on the risk of such chromosomal disorders as Down s syndrome but there is a small risk of other genetic disorders for men of advanced years. These are the autosomal dominant conditions an example of which is dwarfism. 2

3 Finally, there are changes in the eggs from ovaries with advancing age that make them less capable of fertilisation by sperm both in vivo (natural conceptions) and in vitro (test tube conception - IVF). Genetic Counselling Because children born to women more than 40 have a higher risk of chromosomal problems, it is sensible to seek information about those tests that are available to detect these conditions. These include chorionic villus sampling and amniocentesis, both of which involve direct sampling of the pregnancy tissue or fluids and which provide a definite diagnosis. One alternative, which involves no risk of miscarriage, is a blood test for the mother or an ultrasound examination of the pregnancy but these provide only an estimate of the chance that a chromosomal abnormality is present. It is therefore necessary to think through all of the implications in having such tests. These include the risk of the test itself causing a miscarriage and the possible medical and psychological consequences of termination of the pregnancy that is offered when an abnormality is detected. Table 1 Rate of Miscarriage by Maternal Age Age in Years Spontaneous Miscarriage (%) > Medical Counselling Women with some medical disorders, such as high blood pressure or diabetes, may benefit from consultation with an obstetrician before attempting pregnancy. This will provide information regarding the course of pregnancy in the presence of such medical conditions. It is desirable that these types of health problems are completely evaluated and well controlled prior to attempting pregnancy. Even in the absence of pre-existing high blood pressure and diabetes, these conditions develop more commonly in women who conceive after age 35 years. As a result, special monitoring and testing may be recommended during the pregnancy. One item of advice is common to women of all ages. This relates to the desirability of increasing the intake of Folic Acid in the months before and early weeks of any pregnancy by either alteration in diet or by vitamin supplementation. 3

4 Table 2 Mother's Age at expected date of delivery (Years) Risk of Baby with Chromosomal Abnormality by Maternal Age Chance of live-born baby with Down s Syndrome Chance of live-born baby a chromosomal abnormality :1420 1: :1250 1: :1140 1: :384 1: :307 1: :242 1: :189 1: :146 1: :112 1: :85 1: :65 1: :49 1: :37 1: :30 1: :23 1: :18 1: :14 1: :11 1:8 Treatment options and alternatives when there are Fertility Problems Once the appropriate testing has been completed then possible treatment plans will be discussed. It is important to remember that any treatments raised are options to be considered. Some couples decide that the best option is not to undergo infertility treatment but to remain childless (or childfree!). Modern infertility therapy currently allows women many more options than were possible in the past. However, these treatments may have significant financial, emotional and social demands. If a cause for infertility is identified, a specific treatment may be possible. However, sometimes no specific problem is identified and the infertility is unexplained. With unexplained infertility, or when traditional treatments have failed, assisted conception in the form of SIUI (ovarian stimulation and insemination into the uterus with husband s sperm) with or without ovulation enhancement using fertility drugs or in vitro fertilisation (IVF) may be offered. It is best to discuss the success rates of any recommended therapy and decide in advance how many treatment cycles will be attempted before getting on a roundabout that increases in complexity, risks, cost and desperation. Egg Donation The treatment options are limited for women over 40 who have not succeeded with other therapies and for women with evidence of an early menopause (premature ovarian failure). One option involves the use of 4

5 eggs donated by another woman. Eggs from a younger woman are more likely to result in pregnancy and less likely to end in miscarriage even when carried by an older woman. In the case of women who have no ovarian function due to an early menopause, this treatment offers the only chance for pregnancy. The process of egg donation can involve either a known donor, such as a relative or friend, or an unknown (anonymous) donor. Whether using a known or anonymous donor, couples need to feel comfortable with the idea of using eggs from another woman. If this concept is not acceptable to either partner, then the use of donor eggs should not be considered. In a donor egg cycle, the woman donating eggs will be given medications to stimulate the production of multiple eggs. These eggs are taken from the donor by aspiration through the vagina with ultrasound guidance. Egg donors should be aged 35 years of age or less but, even for such women, the number of eggs available for fertilisation after hormonal stimulation and recovery varies from a few to many. Stimulation of more than 20 developing eggs is medically hazardous to the donor. After the eggs are obtained from the donor, they are fertilised in the laboratory with sperm from the recipient's partner. Under normal circumstances about 80% of the eggs can be expected to fertilise. Two to three days after fertilisation the embryos may be transferred to the recipient's uterus or frozen for a period while further infection screening tests are carried out on the donor. Such frozen embryos may provide several attempts at pregnancy for the recipient over several months or even years. However, it needs to be appreciated that the chance of a take home baby is no more than 10-15% for each embryo transferred. Indeed, if fewer than six embryos are available, then there is a 50% chance that the donation will not be successful in an ongoing pregnancy. The option to receive eggs donated by a younger woman offers women over 40 the opportunity to experience pregnancy and give birth. The child will not be the genetic offspring of the recipient and special thought must be given before deciding on egg donation. Many programs recommend counselling to understand the ethical, legal, psychological and social issues involved in the use of donor eggs and/or donor sperm. Surrogacy A surrogate is a woman who agrees to become pregnant for a couple using the male partner's sperm and her own egg (traditional surrogate) or using the male partner's sperm and the female partner's egg (gestational carrier). She also agrees to give up the baby to the couple at birth. Surrogacy is the only option for women who have had a hysterectomy or cannot become pregnant for other medical reasons. Surrogacy is a controversial option that remains largely untested in society and it is desirable to obtain legal advice before proceeding. Commercial surrogacy i.e. when the surrogate is paid is illegal in Australia and Medicare will not pay for IVF treatment for surrogacy. As with egg donation the need for careful counselling of all parties involved is most important. Adoption and Foster Care Another option for having a family is adoption. Agencies have different rules regarding age and are now more receptive to older couples. There are generally no age restrictions for private adoptions. In international adoptions, some countries even prefer older parents. Foster care can offer the option to nurture a child without making a lifetime commitment and can also help couples decide if adoption is right for them. Childfree Living It is important that couples consider the option of remaining childfree if they are unable to have their own child or if they decide to forego infertility treatment. Couples will need to grieve their loss and look at alternative ways to achieve personal growth. Some people pursue a new career, a charity, a hobby or adopt a special project. Both partners will need to discuss what is best for them. A fertility centre counsellor can help a woman or a couple explore these issues. Acknowledgement: With the assistance of American Society for Reproductive Medicine and the NSW Genetics Service patient information series. 5

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