Age Fertility

AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Formerly The American Fertility Society

AGE AND FERTILITY A Guide for Patients

PATIENT INFORMATION SERIES

Published by the American Society for Reproductive Medicine under the direction of the Patient Education Committee and the Publications Committee. No portion herein may be reproduced in any form without written permission. This booklet is in no way intended to replace, dictate, or fully define evaluation and treatment by a qualified physician. It is intended solely as an aid for patients seeking general information on issues in reproductive medicine. Copyright 1996 by the American Society for Reproductive Medicine.

AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Formerly The American Fertility Society

AGE AND FERTILITY AGuide for Patients A glossary of italicized words is located at the end of this booklet.

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. Also, information in the media about assisted reproductive technologies may give women an unrealistic sense of security that childbearing can be delayed. It is important that women realize that age may affect their ability to conceive and have a healthy pregnancy. It is also important to be aware of possible tests and treatments which may be offered to older women to assist them in achieving pregnancy. This booklet will discuss the realities and challenges women may face when considering pregnancy after the age of 40.

FERTILITY AFTER 40 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 under 30, but only 5 percent in women over 40. Even with advanced infertility treatments, such as in vitro fertilization (IVF), fertility decreases and the chance of miscarriage increases in women after age 40. There are several explanations for this change in fertility, including medical conditions, changes in ovarian function, and alterations in the eggs released by the ovaries. Aging 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 aging. The testes tend to get slightly smaller and softer with age. Sperm morphology (shape) and motility 3

(movement) also tend to decline. 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 aging. Often there is a slight decrease in a man’s testosterone level which can cause a decrease in libido (sexual drive). Men may have difficulty achieving and/or maintaining erections as they age. These changes in testosterone, libido, and sexual functioning may not be strictly due to aging, but can be caused by illness, stress, or reactions to medications, all of which tend to occur more frequently as men get older. Furthermore, not all men experience significant changes in sexual functioning as they age, especially men who maintain good health over the years. If a man does have problems with libido or erections, there are treatments available and he should see a primary care physician or urologist to discuss his options.

MEDICAL CONDITIONS By the time a woman is 40, she has had more time to develop gynecologic disorders, such as pelvic infections and endometriosis, which may decrease fertility. For more information on endometriosis, refer to the ASRM patient information booklet titled Endometriosis. Her partner may have developed a sperm problem which affects the couple's chances of pregnancy. Common fertility tests, such as a semen analysis for the man and a hysterosalpingogram (HSG) or laparoscopy for the woman, may be ordered to diagnose some of these conditions. Although most infertility specialists recommend that couples attempt pregnancy for at least one year prior to undergoing these tests, women over 40 may undergo tests after as little as six months of attempting conception. Refer to the ASRM patient information booklet titled Infertility: An Overview for more information regarding the infertility evaluation.

OVARIAN CHANGES Although medical disorders may cause infertility in couples over 40, more often the decreased chance for pregnancy is due to the normal changes which occur in the woman's ovaries with aging. 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 hormone, estrogen, 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 40 and 56 years of age, 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 levels of these hormones in the bloodstream increase in an attempt to stimulate the ovaries. An 4

elevated blood FSH level on the third day of the menstrual cycle 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 estrogen and progesterone produced by the ovary. The menstrual cycle may become shorter and eventually the ovaries may not release an egg, resulting in a skipped period. In addition, the hormones estrogen and progesterone are critical for the normal development of the lining of the uterus (endometrium), where the early embryo must attach in order to grow. A reduction in hormones from the ovaries with age is therefore thought to decrease the chances for pregnancy.

Changes in Eggs As a woman ages, the remaining eggs in her ovaries also age, making them less capable of fertilization by sperm. In addition, fertilization of these eggs is associated with a higher risk of genetic disorders. For example, disorders involving the chromosomes, such as Down Syndrome, are more common in children born to older women. There is a continuing increase in the risk of these chromosomal problems as women age (Table 1). When eggs with chromosomal problems are fertilized, they are less likely to survive and grow. For this reason, women who are over 40 are at increased risk for miscarriage (Table 2). The source of the decreased pregnancy rates in women over 40 is thought to be due, in large part, to the increase in the number of eggs with chromosomal problems. When eggs are collected from women in their 20s and 30s, fertilized, and placed in the uterus of a woman over 40, the chance for pregnancy in the older woman is much higher than she could expect if she had used her own eggs. The TABLE 1. Risk of Chromosomal Abnormality in Newborns By Maternal Age Maternal Age (years) 20 25 30 35 40 41 42 43 44 45 46 47 48 49

Risk for Total Risk for Chromosomal Down Syndrome Abnormalities 1/1,667 1/526 1/1,250 1/476 1/952 1/385 1/378 1/192 1/106 1/66 1/82 1/53 1/63 1/42 1/49 1/33 1/38 1/26 1/30 1/21 1/23 1/16 1/18 1/13 1/14 1/10 1/11 1/8

This table originally appeared in “Maternal Fetal Medicine: Practice and Principles.” Creasy and Resnick, eds. W.B. Saunders, Philadelphia, PA. 1994:71. Reproduced with permission of the publisher.

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success of 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 except donor egg will be less successful in women over 40. TABLE 2. Risk of Miscarriage with Increased Age Maternal Age (years) 15-19 20-24 25-29 30-34 35-39 40-44 ≥45

Spontaneous Abortion (%) 9.9 9.5 10.0 11.7 17.7 33.8 53.2

This table originally appeared in “Reproductive Potential in the Older Woman” by P.R.Gindoff and R. Jewelewicz. Fertility and Sterility. 46:989;1986. Reproduced with permission of the publisher.

INFERTILITY EVALUATION If an older woman decides to attempt pregnancy, it is important that she seek the advice of her physician. If the doctor identifies any medical problem which may affect her chances of getting pregnant, or if she has been trying to conceive for more than six to 12 months, she may be referred to an infertility specialist. The chances for pregnancy decrease with age, so it is usually recommended that any necessary tests be performed promptly. Most infertility testing can be completed in one to three months, and appropriate treatment can be started immediately after the evaluation. In addition to the usual infertility tests (as described in detail in the ASRM patient information booklet titled Infertility: An Overview), the infertility specialist may suggest a blood test to examine the levels of FSH and/or estradiol early in the menstrual cycle. The levels of these hormones may suggest whether the ovaries are becoming less responsive to the hormones (FSH and LH) that induce ovulation. Although pregnancy rates are lower in all women over 40, women with high levels of FSH and/or estradiol early in their menstrual cycle have a markedly decreased chance for pregnancy. Knowing this information may help women decide if infertility treatment is worthwhile and/or may influence the treatment which the infertility specialist recommends.

Genetic Counseling Because children born to women over 40 have a higher risk of chromosomal problems (Table 1), these women may wish to talk with their physician or a genetic counselor prior to attempting pregnancy. They will provide information regarding the chances of having a child with a chromosomal problem, such as Down Syndrome, and the choices for prenatal testing if pregnancy is achieved. Chorionic 6

villus sampling and amniocentesis are two methods of prenatal testing. Many parents want to know this information so they can make informed decisions about the pregnancy.

Medical Counseling Women with some medical disorders, such as high blood pressure or diabetes, may also wish to talk with an obstetrician or perinatologist before attempting pregnancy. This will provide information regarding the course of pregnancy for a woman with such a medical condition. It is important for these types of health problems to be well controlled prior to attempting pregnancy. For this reason, the obstetrician may suggest a change in medication or general health care prior to attempting pregnancy. Even without pre-existing high blood pressure and diabetes, these conditions develop more commonly in women who conceive after age 35. As a result of this increased risk, special monitoring and testing may be recommended during the pregnancy.

TREATMENT OPTIONS AND ALTERNATIVES Once the appropriate testing is completed, the physician will discuss the possible treatment plans. It is important to remember that any treatments discussed are options to be considered. Some couples decide that the best option is not to undergo infertility treatment but to consider alternatives such as adoption or child-free living. 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, the physician may suggest a specific treatment. However, sometimes no specific problem is identified and the infertility is unexplained. With unexplained infertility, or when traditional treatments have failed, advanced infertility therapies such as superovulation with timed intrauterine insem-ination (SO/IUI), gamete intrafallopian transfer (GIFT), or IVF may be suggested. As with any treatment, age affects the chance for pregnancy. It is useful to ask the physician to discuss the success rates of any recommended therapy and how many treatment cycles he or she would recommend. For more information on assisted reproductive technologies, refer to the ASRM patient information booklet titled IVF & GIFT: A Guide to Assisted Reproductive Technologies.

Egg Donation The treatment options are limited for women over 40 who have not succeeded with other therapies or for women with evidence of early menopause (premature ovarian failure). One option for older women involves the use of 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 early menopause, this treatment offers the only chance for pregnancy. For more information on early menopause, refer to the ASRM patient information booklet titled Early Menopause. 7

The process of egg donation can involve either a known donor, such as a relative or friend, or an unknown (anonymous) donor. Often there is an attempt to match physical characteristics with that of the donor. Whether using a known or an 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. During the time that the egg donor is receiving these medications, the recipient will be given hormone therapy to prepare her uterus to receive the embryos. After the eggs are obtained from the donor, they are fertilized in the laboratory with sperm from the recipient’s partner (or donor sperm). One to three days after fertilization, the embryos are transferred to the recipient’s uterus. Any embryos which are not transferred may be frozen (cryopreserved). This allows another opportunity for a future pregnancy attempt. 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 counseling to understand the ethical, legal, psychological, and social issues involved in the use of donor eggs and/or donor sperm. There are many facts that should be considered prior to selecting a donor egg program. Often programs have more women requesting egg donation than they have available donors. For this reason, the wait for a donor may be long. Couples also will want to know how the donors are recruited, what screening is required, and what information they will receive about the donor. Also important is the average cost of a treatment cycle and the success rate of the program (percentage of children born or ongoing pregnancies for each cycle started). Couples who decide to use a known donor, such as a relative or friend, should be sure that everyone involved is thoroughly informed about the treatments which will be required. Using a known donor raises special issues about parenting which must be discussed. All parties must understand how this will impact the family and what they will tell the child. Counseling can help explore these issues and prepare for the future. It is best to consider these issues long before starting a donor egg treatment cycle. All parties should consult an attorney before proceeding with donor egg.

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 a controversial option, but it can offer women over 40 an opportunity to have a child who is genetically linked to the male partner. It is also an option for women who have had a hysterectomy or cannot become pregnant for medical reasons. It is critical that the surrogate be carefully screened psychologically, medically, and legally. For more information on 8

surrogacy, refer to the ASRM patient information booklet titled Third Party Reproduction.

Adoption and Foster Care

Another option for having a family is adoption. Agencies have different rules regard-ing age and are now more receptive to older couples. There are generally no age restric-tions for private adoptions. In international adoptions, some countries even prefer older parents. For more information on adoption, refer to the ASRM patient information booklet titled Adoption. 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. Social Service agencies often seek couples to be foster parents.

Child-Free Living It is important that couples consider the option of remaining child-free 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 new personal growth. Some people pursue a new career, hobby, or adopt a special pet. Both partners will need to discuss what is best for them.

SUPPORT GROUPS Infertility at any age is a stressful experience, and counseling or support groups can be helpful. The intrusive nature of infertility testing and treatment can make many couples feel out of control. They may also feel like they are on an emotional roller coaster, with feelings peaking and plunging at different times of the month or treatment cycle. Feelings of sadness, anger, blame, guilt, depression, and loss can be overwhelming at times. These are normal feelings and couples can cope by discussing their concerns with each other, the medical staff, and supportive people in their life. Age is a factor in the decreased chance of success with any infertility treatment. If pregnancy occurs, the older woman also has an increased chance of miscarriage, which can be emotionally devastating to couples who have invested so much of them-selves in achieving a pregnancy. It is important to have realistic expectations with any infertility treatment and guarded optimism when pregnancy is achieved. Because infertility can be so stressful and requires complex decisions, it may be helpful to consider joining a support group or seeing a therapist with special infertility training. Couples can ask their physician for the names of therapists or contact RESOLVE, a national infertility support group (see Resources section at the end of this booklet). For more information on the psychological aspects of infertility, refer to the ASRM patient information booklet titled Infertility: Coping and Decision Making.

SUMMARY There is a biological decrease in fertility with advancing age. For women who 9

decide to become pregnant after age 40, it is important that they obtain information on appropriate testing and treatment while remaining realistic about the chances for success with any infertility therapy. Options such as egg donation offer opportunities for older women who previously had a limited chance for pregnancy and childbirth. However, these choices may not be right for everyone and must be carefully con-sidered. By learning about all of the options and being aware of their own needs and goals, potential parents will be prepared to make the best decisions.

RESOURCES RESOLVE, Inc. 1310 Broadway Somerville, MA 02144-1731 (617)623-0744

The National Council for Adoption 1930 17th Street NW Washington, D.C. 20009 (202)328-1200

SHARE Pregnancy and Infant Loss Support, Inc. St. Joseph Health Center, 300 First Capitol Drive St. Charles, MO 63301-2893; (314)947-6164

GLOSSARY Amniocentesis. A procedure in which a small amount of amniotic fluid is removed through a needle from the fetal sac at about 16 weeks into a pregnancy. The fluid is studied for chromosomal abnormalities which may affect fetal development. Chorionic villus sampling. A procedure in which a small sample of cells is taken from the placenta early in a pregnancy for chromosomal testing. Chromosomes. Rod-shaped structures located in the nucleus of a cell which contain hereditary (genetic) material. Humans have 23 pairs of chromosomes (46 total). Two of the 46 are the sex chromosomes, which are the X and Y chromosomes. Normally, females have two X chromosomes and males have one X and one Y chromosome. Cryopreserved. Freezing sperm or embryos to store them for future use. At present, eggs cannot be cryopreserved because freezing damages them. Donor egg. The eggs taken from the ovaries of a fertile woman and donated to an infertile woman to be used in an assisted reproductive technology procedure using IVF or GIFT. Down Syndrome. A genetic disorder caused by the presence of an extra chromosome 21 and characterized by mental retardation, abnormal facial features, and medical problems such as heart defects. Early menopause. Also called premature ovarian failure. Cessation of menstrual periods due to failure of the ovaries before age 40. The average age of menopause in the United States is 51. Egg donation. The process of fertilizing eggs from a donor with the male partner’s sperm in a laboratory dish and transferring the resulting embryos to the female partner’s uterus. The female partner will not be biologically related to the child but will be the birth mother on record. The male partner will be biologically related to the child. 10

Embryo. The earliest stage of human development arising after the union of the sperm and egg (fertilization). Endometriosis. A condition when endometrial tissue, which normally lines the uterus, develops outside of the uterine cavity in abnormal locations such as the ovaries, fallo-pian tubes, and abdominal cavity. Endometriosis can grow with hormonal stimulation and cause pain, inflammation, and scar tissue. It may also be associated with infertility. Endometrium. The lining of the uterus that is shed each month as the menstrual period. As the monthly cycle progresses, the endometrium thickens and thus provides a nourishing site for the implantation of a fertilized egg. Estradiol. The predominant estrogen (hormone) produced by the follicular cells of the ovary. Estrogen. The female sex hormones produced by the ovaries which are responsible for the development of female sex characteristics. Estrogens are largely responsible for stimulating the uterine lining to thicken during the first half of the menstrual cycle in preparation for ovulation and possible pregnancy. They are also important for healthy bones and overall health. A small amount of these hormones are also produced in the male when testosterone is converted to estrogen in fat cells. Follicle stimulating hormone (FSH). In women, FSH is the pituitary hormone responsible for stimulating follicular cells in the ovary to grow, triggering egg development and production of the female hormone estrogen. In the male, FSH is the pituitary hormone that travels through the bloodstream to the testes and helps stimulate them to manufacture sperm. Gamete intrafallopian transfer (GIFT). An assisted reproductive technology that involves surgically removing eggs from a woman’s ovary, combining them with sperm, and immediately injecting the eggs/sperm mixture into the fallopian tube. Fertilization then hopefully takes place inside the fallopian tube. One disadvantage of GIFT is the inability to know whether or not fertilization took place if the woman does not become pregnant. Hypothalamus. A thumb-sized area in the base of the brain that controls many functions of the body, regulates the pituitary gland, and releases gonadotropin releasing hormone (GnRH). Hysterosalpingogram (HSG). An x-ray procedure in which a special media (a dyelike solution) is injected through the cervix into the uterine cavity to illustrate the inner shape of the uterus and degree of openness (patency) of the fallopian tubes. In vitro fertilization (IVF). A method of assisted reproduction that involves combining an egg with sperm in a laboratory dish. If the egg fertilizes and begins cell division, the resulting embryo is transferred into the woman’s uterus where it will hopefully implant in the uterine lining and further develop. IVF may be performed in conjunction with medications that stimulate the ovaries to produce multiple eggs in order to increase the chances of successful fertilization and implantation. IVF bypasses the fallopian tubes and is often the treatment choice for women who have badly damaged or absent tubes. Laparoscopy. The insertion of a long, thin, lighted, telescope-like instrument called 11

a laparoscope into the abdomen through an incision usually in the navel to visually inspect the contents of the pelvic and abdominal cavities. Other small incisions may also be made and additional instruments inserted to facilitate diagnosis and allow surgical correction of abnormalities. The surgeon can sometimes remove scar tissue and open closed fallopian tubes during this procedure. Luteinizing hormone (LH). In women, the pituitary hormone that triggers ovulation and stimulates the corpus luteum of the ovary to secrete progesterone and androgens during the second half of the menstrual cycle. In the male, LH is the pituitary hormone which stimulates the testes to produce the male hormone testosterone. Menopause. Natural cessation of ovarian function and menstruation. Menopause can occur between the ages of 42 and 56 but usually occurs around the age of 51, when the ovaries stop producing eggs and estrogen levels decline. Oocytes. Eggs; also called ova. Perinatologist. A maternal-fetal medicine specialist. Pituitary gland. A small hormone-producing gland just beneath the hypothalamus in the brain which controls the ovaries, thyroid, and adrenal glands. Ovarian function is controlled through the secretion of follicle stimulating hormone (FSH) and luteiniz-ing hormone (LH). Disorders of this gland may lead to irregular or absent ovulation in the female and abnormal or absent sperm production in the male. Premature ovarian failure. Cessation of menstrual periods due to failure of the ovaries before age 40. Also known as early menopause. Progesterone. A female hormone secreted by the corpus luteum after ovulation during the second half of the menstrual cycle (luteal phase). It prepares the lining of the uterus (endometrium) for implantation of a fertilized egg and allows for complete shedding of the endometrium at the time of menstruation. In the event of pregnancy, the progesterone level remains stable beginning a week or so after conception. Recipient. A person who receives donated eggs, sperm, or embryos. RESOLVE. A national infertility support group. RESOLVE's address is 1310 Broadway, Somerville, Massachusetts 02144-1731; (617)623-0744. Semen analysis. The microscopic examination of semen to determine the number of sperm (sperm count), their shapes (morphology), and their ability to move (motility). Superovulation with timed intrauterine insemination. A procedure to facilitate fertilization. The woman is given ovulation inducing drugs which cause her ovaries to produce multiple eggs. When the eggs are ready to be released, the woman is inseminated with her partner's sperm or donated sperm. Surrogate. A traditional surrogate is a woman who is inseminated with the sperm of a man who is not her partner in order to conceive and carry a child to be reared by the biological (genetic) father and his partner. In this procedure the surrogate is genetically related to the child. The biological father and his partner must usually adopt the child after its birth. Another type of surrogate is a gestational carrier. This process involves implanting a fertilized egg (embryo) into the surrogate’s uterus. In this procedure the surrogate does not provide the egg and is therefore not biologically (genetically) related to the child. 12

Booklets available for purchase through the American Society for Reproductive Medicine:

Adoption (1990) Age and Fertility (1996) Birth Defects of the Female Reproductive System (1993) Donor Insemination (1996) Early Menopause (Premature Ovarian Failure) (1996) Endometriosis (1994) (Also available in Spanish) Fertility After Cancer Treatment (1995) Hirsutism and Polycystic Ovarian Syndrome (1995) Husband Insemination (1996) Infertility: An Overview (1994) (Also available in Spanish) Infertility: Coping and Decision Making (1995) IVF & GIFT: A Guide to Assisted Reproductive Technologies (1995) (Also available in Spanish) Laparoscopy and Hysteroscopy (1995) Male Infertility and Vasectomy Reversal (1995) Menopause (1996) Miscarriage (1995) Ovulation Detection (1995) Ovulation Drugs (1995) Third Party Reproduction (Donor Eggs, Donor Sperm, Donor Embryos, and Surrogacy) (1996) Tubal Factor Infertility (1995) Uterine Fibroids (1993) For copies, ask your physician or contact the ASRM at the address below.

AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Formerly The American Fertility Society

1209 Montgomery Highway • Birmingham, Alabama 35216-2809

AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Formerly The American Fertility Society

1209 Montgomery Highway Birmingham, Alabama 35216-2809 (205) 978-5000

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