Assisted reproduction

Related Terms

Adoption, assisted reproductive technologies, cryptorchism, egg donation, electrolysis, endometriosis, erectile dysfunction, exercise, female infertility, fertility, fragile X syndrome, in vitro fertilization, infertility, Klinefelter's syndrome, male infertility, miscarriage, PCOS, pelvic inflammatory disease, PID, polycystic ovary syndrome, premature ovarian failure, reproductive health.

Background

Fertility conditions may affect both men and women. In fact, approximately 33% of infertility cases occur from a combination of male and female factors. Additionally, approximately 10-15% of couples in the United States are infertile. Infertility is defined as not being able to become pregnant after at least one year of trying.
Approximately 40-50% of infertility cases are caused by female conditions. These include damage or blockage of the fallopian tubes, endometriosis, polycystic ovary syndrome (PCOS), and premature ovarian failure (POF).
The remaining infertility cases are caused by male conditions. These include sperm production problems, health and lifestyle factors, and overexposure to certain environmental elements.
Individuals affected by fertility conditions may be treated with medications and various medical technologies. However, these measures may help treat the symptoms without curing the underlying condition.

Signs and symptoms

Endometriosis: Individuals may experience pelvic pain and cramping that may begin before and continue several days into the menstrual period. Women may also feel lower back and abdominal pain. Additionally, individuals may experience occasional heavy periods (menorrhagia) or bleeding between periods (menometrorrhagia).
Erectile dysfunction: Symptoms associated with erectile dysfunction (ED) include the occasional inability to obtain a full erection, inability to maintain an erection throughout intercourse, and complete inability to achieve an erection. Lack of morning erections are also seen along with a decrease in sex drive (libido).
Polycystic ovary syndrome: Women with (PCOS) usually have the following signs and symptoms: irregular or no menstruation, which is the most common characteristic, signs of excess androgen (male hormone), such as long, coarse hair on the face, chest, lower abdomen, back, upper arms, or upper legs (hirsutism), acne, and male-pattern baldness (alopecia). However, not all women who have PCOS have physical signs of androgen excess. The ability to use insulin effectively is impaired in PCOS and can result in high blood sugar levels and diabetes. Other symptoms that may occur with PCOS include: high blood pressure, high blood cholesterol, elevated levels of C-reactive protein, which may be associated with cardiovascular problems such as heart attack, nonalcoholic steatohepatitis (or fatty liver), and sleep apnea (pauses in breathing during sleep).
Premature ovarian failure: Menstrual periods may become irregular and women may experience hot flashes, night sweats, irritability, vaginal dryness, low sex drive, or trouble sleeping.

Diagnosis

Endometriosis: Endometriosis may be diagnosed by a combination of physical examination findings and diagnostic tests. Typical procedures include a pelvic exam and transvaginal ultrasound. Pelvic laparoscopy may be needed to make a definitive diagnosis, but patients may choose to start treatment without having this procedure performed. Laparoscopy is a surgical procedure performed under either general or local anesthesia. The abdomen is inflated with carbon dioxide through a small incision in the navel, into which an instrument called a laparoscope is inserted to view the abdomen and pelvis. A biopsy may also be performed during this procedure to analyze tissue samples for further diagnosis.
Erectile dysfunction: A medical history includes the frequency and duration of symptoms, the presence or absence of morning erections, and the quality of the relationship with the sexual partner. The sudden onset of erectile dysfunction (ED) in association with normal morning erections suggests ED caused by psychological issues, such as anxiety disorders.
Psychosocial examination, using an interview and a questionnaire, reveals psychological factors. A man's sexual partner may also be interviewed to determine expectations and perceptions during sexual intercourse. Questions about how and when the condition developed, any medications taken, and any other physical conditions or diseases are included. A patient's doctor will also want to discuss recent physical or emotional changes.
Duplex ultrasound is used to evaluate blood flow, venous leak, signs of atherosclerosis (hardening of the arteries), and scarring or calcification of erectile tissue. Erection is induced by injecting prostaglandin (alprostadil or Caverject?, Edex?), a hormone-like stimulator of erection produced in the body. Ultrasound is then used to see vascular dilation and measure penile blood pressure (which may also be measured with a special cuff). Measurements are compared to those taken when the penis is flaccid.
Premature ovarian failure: A blood test may reveal whether the luteinizing hormone (LH) level is normal. LH prompts the mature follicle within the ovary to release an egg and low LH levels may occur in women who have POF.
Polycystic ovary syndrome: There is currently no known specific test that will diagnose PCOS. Therefore, the doctor will usually rule out other disorders. Individuals may have several hormones tested including LH and follicle-stimulating hormone. Since individuals are at an increased risk of developing diabetes and high cholesterol, blood tests may be performed to assess for these conditions.

Complications

Addison's disease: Individuals with POF have a higher incidence of developing Addison's disease. Addison's disease occurs when the small hormone producing gland located above the kidneys (adrenal glands) does not produce adequate amounts of hormones that regulate bodily functions.
Depression: Infertility may cause women to become depressed. Individuals may seek help from support groups to discuss their feelings.
Dyslipidemia: Women with PCOS have a higher risk of developing high cholesterol. This includes increased triglycerides, high LDL (bad) cholesterol, and decreased HDL (good) cholesterol.
Endometrial cancer: Women with PCOS have an increased risk of developing endometrial cancer. Irregular menstrual periods and the absence of ovulation cause women to produce the hormone estrogen, but not the hormone progesterone. Progesterone causes the endometrium to shed its lining each month as a menstrual period. The endometrium becomes thick without progesterone, which can cause heavy or irregular bleeding. Over time, this may lead to cancer.
Impaired glucose tolerance: Individuals with PCOS have a higher risk of developing pre-diabetes. Individuals with pre-diabetes have blood glucose levels that are higher than normal but not high enough for a diagnosis of diabetes. This condition raises the risk of developing type 2 diabetes, heart disease, and stroke. Many individuals with pre-diabetes go on to develop type 2 diabetes within 10 years.
Osteoporosis: Women who have POF may be at a higher risk of developing osteoporosis because they have low estrogen levels.
Psychological issues: Psychological problems may exist along with ED, such as depression, stress, and anxiety.

Treatment

Adoption: Individuals who are infertile may choose adoption rather than assisted reproductive technologies or ovulation medications. Couples may opt for adoption after trying other methods that have failed to work or if they have ethical issues with certain reproductive technologies. There are a variety of options to choose from when adopting, each with different guidelines or legal requirements.
Assisted reproductive technologies: Assisted reproductive technology (ART) has enabled many couples to have their own biological child through a variety of medical advances. A team of healthcare professionals collaborate with the infertile couples with the hopes of achieving pregnancy. There are many ethical questions that arise with the use of ART; many technologies result in "spare" or "leftover" embryos that may then be used for embryonic stem cell research, which is highly controversial.
In vitro fertilization (IVF) is the most effective form of ART. This procedure involves retrieving mature eggs from a woman, fertilizing them with a man's sperm in a dish in a laboratory, and implanting the embryos in the uterus three to five days after fertilization. IVF is used for a variety of fertility conditions including blocked fallopian tubes, endometriosis, ovulation disorders, and male infertility. This procedure has many ethical implications because "spare" or "leftover" embryos are disposed of immediately or frozen.
Intracytoplasmic sperm injection (ICSI) involves injecting a single sperm directly into an egg to achieve fertilization, which is used in combination with IVF. This method improves the probability of fertilization in men with low sperm counts. This is also considered a controversial procedure by some.
Complications of ART may include multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), bleeding or infection, and birth defects. Multiple pregnancy is the most common complication associated with ART. Aborting one or more fetuses may improve the survival odds for the other fetuses, a procedure which has ethical implications. OHSS may occur when the woman's ovaries are stimulated and enlarged, which results in pain and bloating. In severe cases, fluid may build up in the abdominal cavity and chest leading to swelling and shortness of breath. Additionally, fluid accumulation may occur.
Insulin sensitizers: Metformin (Glucophage?) is an oral medication for type 2 diabetes that treats insulin resistance. Evidence suggests that metformin is beneficial in women with PCOS since it improves ovulation and reduces androgen levels. Side effects may include nausea, vomiting, and diarrhea.
Oral contraceptives: Oral contraceptives may be used to regulate the menstrual cycle in women with PCOS. Additionally, oral contraceptives decrease androgen production. Therefore, oral contraceptives may decrease excessive hair growth. Women should discuss possible side effects with a qualified healthcare professional.
Ovulation drugs: Clomiphene citrate (Clomid?) is the most commonly prescribed medication used to stimulate ovulation. Women who conceive with the medication have approximately a 10% chance of having twins. Side effects are common and generally include hot flashes, mood swings, breast tenderness, and nausea. Clomid? is taken orally and causes the pituitary gland to release more follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which increase the development of ovarian follicles that contain eggs. Additionally, Clomid? stimulates ovulation in approximately 80% of patients. It is unknown if the risk of miscarriage is affected by Clomid?.
Reducing excessive hair growth: Eflornithine (Vaniqa?) is a prescription cream that slows facial hair growth in women. Additionally, electrolysis is an option to permanently remove excess hair. This procedure includes inserting a fine needle into the hair follicle and applying an electric current to kill the follicle. This treatment may cause scarring, and skin infections may occur.
Pain medications: Over the counter anti-inflammatory medications such as ibuprofen (Advil?, Motrin?) may relieve the pain associated with menstrual cramps.
Phosphodiesterase-5 inhibitors (PDE-5): Oral medications available to treat erectile dysfunction (ED) and female sexual arousal disorders include sildenafil (Viagra?), tadalafil (Cialis?), and vardenafil (Levitra?). The U.S. Food and Drug Administration (FDA) approved Viagra? in 1998, and it became the first oral medication for ED on the market. Since then, Levitra? and Cialis? have been approved, providing more options for oral therapy. These drugs are chemically known as phosphodiesterase-5 inhibitors (PDE-5). They enhance the effects of nitric oxide, a chemical messenger that relaxes smooth muscles in the penis. This increases the amount of blood flowing into the penis and allows an erection in response to sexual arousal and stimulation. These medications do not automatically produce an erection. Instead they allow an erection to occur after physical and psychological stimulation and arousal. Many men experience improvement in erectile function after taking these medications regardless of the cause of their impotence.
Generally, these medications are absorbed and processed rapidly by the body and are usually taken 30 minutes to one hour before intercourse. Cialis? has been reported in clinical trials to stay in the body longer than the others. It promotes erection within 30 minutes and enhances the ability to achieve erection for up to 36 hours.
Common side effects of phosphodiesterase inhibitors include headache, reddening of the face and neck (flushing), indigestion, and nasal congestion. These drugs may also cause hypotension or low blood pressure. Cialis? may cause muscle aches and back pain, which usually go away on their own within 48 hours.
Medications prescribed for the treatment of erectile dysfunction may cause significant side effects when mixed with certain heart drugs called nitrates, including nitroglycerin (Nitrostat?, Nitro-Bid?), isosorbide mononitrate (Imdur?), and isosorbide dinitrate (Isordil?). Nitrates are often prescribed to reduce chest pain, dilate the blood vessels, and lower blood pressure. Because ED medications also reduce blood pressure, combining these two types of medication can cause a dangerous drop in blood pressure. Experts do not recommend taking sildenafil (Viagra?), vardenafil (Levitra?), or tadalafil (Cialis?) if nitrates are used. If an individual has coronary heart disease (CHD) or has had a heart attack in recent months, he/she should check with a doctor before taking any of these drugs for erectile dysfunction. These medications should also not be used along with certain medications for high blood pressure called alpha blockers.

Integrative therapies

Unclear or conflicting scientific evidence:
Acupuncture: There has been limited research on acupuncture for sexual dysfunction. Currently there is inadequate available human evidence to recommend for or against acupuncture in the treatment of erectile dysfunction. There is inconclusive evidence in support of acupuncture for infertility. There is, however, some support for use of electroacupuncture for pain relief during assisted reproduction therapy, and it may hold some promise for improving pregnancy rates. Additional high quality research is needed in this area.
Astaxanthin: There is currently insufficient available evidence to recommend for or against the use of astaxanthin for male fertility. Additional study is needed in this area.
Coenzyme Q10: There is early evidence that supports the use of CoQ10 in the treatment of increasing sperm count and motility. Better studies are needed before a strong recommendation can be made.
DHEA: DHEA supplementation may be beneficial in women with ovulation disorders. There is currently not enough scientific evidence to form a clear conclusion about the use of DHEA for this condition. Preliminary evidence suggests that DHEA may offer some benefit to individuals with erectile dysfunction. Well-designed clinical trials, with appropriate endpoints are required before recommendations can be made.
Dogwood: In limited available study, a traditional Chinese herbal combination containing dogwood seems to have helped with postmenopausal levels of follicle stimulating hormone and luteinizing hormone in order to achieve pregnancy. Although this result is interesting, further research is needed in this area.
Green tea: Early research using a combination product called FertilityBlendT has been associated with some success in helping women to conceive. Further well-designed research on green tea alone for this use is needed before a conclusion can be drawn.
Hypnosis: Based on early evidence, hypnosis may improve the in vitro fertilization-embryo transfer cycle. Additional study is needed before a firm conclusion can be drawn.
L-Carnitine: Early evidence shows a positive effect for carnitine and/or acetyl-L-carnitine in terms of increased sperm motility. However, additional study is needed before a firm conclusion can be made.
Lycopene: Based on early study, taking lycopene seems to have a role in the management of idiopathic male infertility. Further research is needed to confirm these results.
Maca: Maca has been traditionally used in Peru to enhance fertility of both people and animals. Maca may improve semen quality; however, additional study is needed to confirm this finding.
Prayer: The potential effect of intercessory prayer on pregnancy rates in women being treated with in vitro fertilization-embryo transfer has been studied. Preliminary results seem positive, but further research is necessary.
Psychotherapy: Group and individual/couple psychotherapy may reduce depression and anxiety associated with infertility. However, psychotherapy may not improve fertility rates. More and better-designed studies are needed in this area.
Pycnogenol: Human studies report that Pycnogenol? may improve sperm quality and function in sub-fertile men. Further research is needed to confirm these results.
Selenium: Selenium supplementation has been studied for male infertility and sperm motility with mixed results. Evidence is currently lacking regarding potential effects on female infertility.
Tribulus: Although results from early investigating the effects of Tribulus terrestris are encouraging, larger studies of better design are needed in order to evaluate the effectiveness of Tribestan? in treatment of female infertility. Although Tribestan? seems to increase sperm count and viability and increase libido, its effectiveness in the treatment of male infertility remains inconclusive, due to a lack of well-designed clinical trials.
Zinc: Many studies report beneficial results of zinc supplements on infertility, as expressed in improved sperm quality and number, although this effect may depend on the cause of infertility. A minor increase in abnormal spermatozoa in subfertile males taking zinc was noted in limited study. Additional research is needed before a firm conclusion can be drawn.
Fair negative scientific evidence:
Arginine: Although there are several studies in this area, it is not clear what effects arginine has on improving the likelihood of getting pregnant. Early evidence does not support the finding that arginine has any benefits in women who are undergoing in vitro fertilization or in men with abnormal sperm.
Probiotics: Probiotics have been used in the vagina immediately after oocyte retrieval during IVF, but they do not appear to have an effect on vaginal colonization or pregnancy rate in IVF cycles.

Prevention

Men should avoid wearing tight underwear since it may affect the ability of the sperm to move and fertilize an egg.
It is important to maintain a normal body weight since being overweight or underweight may affect hormone production and may cause infertility.
Individuals should avoid drug and tobacco use and excessive alcohol consumption, as these may contribute to infertility.
Women who are trying to become pregnant should limit their caffeine intake to one to two cups of coffee a day.
Individuals should engage in regular exercise. However, intense exercise which leads to irregular menstrual periods may impair fertility.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American Academy of Family Physicians. .
American College of Obstetricians and Gynecologists. .
American Pregnancy Association. .
American Society for Reproductive Medicine. .
Bertone-Johnson ER, Hankinson SE, Bendich A, et al. Calcium and vitamin D intake and risk of incident premenstrual syndrome. Arch Intern Med. 2005;165(11):1246-52.
Farshchi H, Rane A, Love A, et al. Diet and nutrition in polycystic ovary syndrome (PCOS): Pointers for nutritional management. J Obstet Gynaecol. 2007 Nov;27(8):762-73.
Levine D. Ectopic pregnancy. Radiology. 2007 Nov;245(2):385-97.
National Fragile X Foundation. .
National Institute of Child Health and Human Development. .
Natural Standard: The Authority on Integrative Medicine. .
Rosano GM, Vitale C, Marazzi G, et al. Menopause and cardiovascular disease: the evidence. Climacteric. 2007;10 Suppl 1:19-24.
Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol. 2008 Jan 24 [Epub ahead of print].

Types and causes

General: Many factors may contribute to male and female infertility, including genetic disorders or health conditions.
Male infertility:
Cancer treatment: Radiation and chemotherapy treatment may have a large impact on sperm production. The risk of infertility depends on how close the radiation treatment is to the testicles.
Cryptorchism: Cryptorchism is a condition where the testes do not descend into the scrotum, which is the loose sac of skin hanging behind the penis. The temperature in the scrotum is lower than the body temperature and therefore the sperm can survive.
Erectile dysfunction: Erectile dysfunction (ED), sometimes called impotence, is the repeated inability to get or keep an erection firm enough for sexual intercourse. ED may affect fertility. Estimates suggest that between 15 and 30 million (20-40%) Americans suffer from ED. There are approximately 26 new cases annually of ED in the United States per 1,000 men who are 40 to 69 years of age. Over 150 million men worldwide suffer from ED.
Klinefelter's syndrome: Klinefelter's syndrome, also known as XXY condition, is a genetic disorder where men have an extra X chromosome. Normally, men only have one X chromosome in each cell. Since males affected by Klinefelter's syndrome have low testosterone levels, they are more likely to be infertile. Males who have Klinefelter's syndrome may demonstrate the following physical characteristics: small testes and penis, small amounts of hair in the pubic, armpit, and facial regions, enlarged breasts (gynecomastia), tall stature, and unusual body proportions (long legs, short trunk).
Lifestyle factors: Lifestyle choices that contribute to heart disease and vascular problems also raise the risk of erectile dysfunction. Since an erection is dependent upon proper blood flow in the penis, heart diseases and vascular (blood vessel) problems that inhibit blood flow may contribute to erectile dysfunction (ED). Smoking, being overweight, eating unhealthy foods (such as a high fat diet), and avoiding exercise are related to an increase in symptoms of ED.
Medical conditions: ED occurs more often in those with diabetes. Diabetes can cause a condition called neuropathy, which is damage to the nerves throughout the body, including the penis. Damaged nerves cannot communicate properly with the brain. So, even though sexual stimulation occurs, nerve damage prevents the information from being relayed to the penis and it does not become erect. In addition, poor blood sugar control can inhibit nitric oxide production. Lack of nitric oxide can prevent the pressure of blood in the corpora cavernosa (chambers in the penis containing blood vessels) from increasing enough to close off penile veins, allowing blood to flow out of the penis instead of remaining trapped for an erection. Blood vessels can also become narrowed or hardened (atherosclerosis) by conditions that often accompany diabetes, such as coronary heart disease (CAD). When atherosclerosis occurs in arteries that supply the penis or pelvic area, sexual function may be disrupted.
Spinal cord and brain injuries such as paraplegia (lower part of the body is paralyzed), quadriplegia (paralysis of both limbs), and stroke (lack of blood flow and oxygen to the brain that causes nerve and blood vessel damage) can cause impotence when they interrupt the transfer of nerve impulses from the brain to the penis. Other nerve disorders, such as multiple sclerosis (MS, an autoimmune disease that affects the nervous system), Parkinson's disease (a degenerative disorder of the nervous system causing uncontrollable shaking), and Alzheimer's disease (a brain disorder characterized by dementia), may also result in ED.
Smoking: Smoking is perhaps the most significant risk factor for developing ED. Cigarette smoking can repeatedly produce a temporary rise in blood pressure (BP), restricting blood flow to various areas of the body including the penis. When the blood vessels in the pelvic and groin area are narrowed, that contributes to reduced penile blood flow. The more a man smokes, the higher are his chances for developing erectile dysfunction; this is especially the case in men over 50 years of age. Men who smoke more than 20 cigarettes daily have a 60% higher risk of ED compared to men who never smoke. Among men who have never smoked, 12% have had erection problems.
Stress: Sperm count may decrease when an individual experiences emotional stress.
Substance abuse: Heavy or chronic (long-term) use of alcohol, marijuana, heroin, cocaine, methamphetamine, or other drugs often causes ED and decreased sexual drive.
Female infertility:
Caffeine intake: There is conflicting evidence as to whether consuming too much caffeine may be associated with decreased fertility. Additionally, studies suggest that high caffeine intake may increase the risk of miscarriage.
Endometriosis: Endometriosis is characterized by the implantation and growth of uterine tissue outside of the uterus; it often causes severe pain. It affects the function of the ovaries, uterus, and fallopian tubes and may lead to infertility.
Pelvic inflammatory disease: Pelvic inflammatory disease (PID) is an infection of the female reproductive organs that causes pain and swelling. If left untreated, PID may cause scarring and permanently damage to the reproductive organs. Without treatment, some patients may become infertile or experience complications during pregnancy. PID usually develops when a sexually transmitted bacteria enters the uterus and reproduces in the upper genital tract. The most common bacteria that cause PID also cause the sexually transmitted diseases (STDs) gonorrhea and chlamydia.
Polycystic ovary syndrome (PCOS): Polycystic ovary syndrome (PCOS) is a common condition characterized by irregular menstrual periods, excess hair growth, and obesity, though it can affect women in a variety of ways. A cyst is a closed sac- or bladder-like structure that is not a normal part of the tissue where it is found. PCOS affects about one in 10 women in the United States and is a leading cause of infertility in women.
Premature ovarian failure (POF): Premature ovarian failure (POF) occurs when the ovaries stop working normally in women under the age of 40. Approximately 250,000 women under the age of 40 in the United States have POF. POF is sometimes referred to as premature menopause, but there is a distinct difference. Premature menopause occurs when the menstrual period stops completely. However, women who develop POF may still have irregular menstrual periods. Between five and 10 percent of women with POF may become pregnant because the ovaries may still release eggs.
Thyroid problems: Individuals who have too much thyroid hormone (hyperthyroidism) or too little thyroid hormone (hypothyroidism) may develop fertility problems.