What is Infertility?
Infertility is defined as a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse. Males are the primary cause of infertility about 25% of the time and a contributing cause an additional 25% of the time.
In 2017 an international group of professional fertility organizations also included those who could not get pregnant due to an impairment of a person’s capacity to reproduce either
as an individual or with his/her partner. This expanded definition was important because it includes single people, those in the LGBTQ+ community and everyone who wants to found a family.
Causes and Risks Associated with Infertility
Some of the most common causes of female infertility are hormonal problems, irregular ovulation, polycystic ovarian syndrome (PCOS), blocked fallopian tubes, adhesions in the pelvis (from sexually transmitted infections or abdominal surgery or infection), endometriosis, fibroids, uterine abnormalities, and genetic factors. Male problems such as low sperm count, sperm motility (the ability to move efficiently) or abnormal sperm morphology (irregular shaped sperm) can cause infertility in men. Causes of male infertility include abnormal sperm production or function due to undescended testicles, genetic defects, health problems such as diabetes, or infections such as chlamydia, gonorrhea, mumps or HIV. Enlarged veins in the testes (varicocele) also can affect the quality of sperm. Other factors include drug or alcohol use and obesity. Sometimes people cannot get pregnant because of an inability to have intercourse or abnormalities of the penis, vagina and cervix.
Lifestyle and Risk Factors That Affect Fertility
There are a number of lifestyle factors that couples can change which may improve their reproductive health and ability to have children.
- Reduce Caffeine and Alcohol Consumption
- Maintain a Healthy Weight and Diet
- Don’t Smoke /Quit Smoking
- Practice Safe Sex (Sexually transmitted diseases are leading causes of infertility)
- Avoid environmental toxicants
Infertility Diagnosis and Tests for Women and Men
There are a number of diagnostic tests available to help pinpoint the cause of infertility in both women and men. After a couple has undergone evaluation through a comprehensive physical exam and medical history, a fertility doctor will recommend specific diagnostic tests.
For the diagnosis of infertility in women, doctors generally check the following areas: the female hormone system and ovarian reserve, the female pelvis, the vagina and cervix. Semen analysis is conducted to diagnose male infertility. Depending on the results, additional tests may be required for both women and men.
Endocrine System Tests
The endocrine system includes all the hormone-producing glands in the body that regulate the body’s growth, metabolism and sexual development. Sometimes infertility is due to problems in the endocrine system, and the fertility specialist may perform various tests, which include:
1) Basal Body Temperature Charting (BBT)
BBT charts help predict the time of ovulation. They can also indicate whether or not there are problems with ovulation. Higher levels of progesterone cause the body temperature to increase slightly (about 0.5F to 1F). To create a BBT chart, a woman must record her temperature every morning before getting out of bed.
- A normal BBT includes a slight increase in temperature between days 10 through 21 of the ovulation cycle.
- BBT that shows a relatively constant temperature indicates an absence of ovulation.
There are many tests that help identify the timing of ovulation, such as Ovulation Predictor Kits (OPK) which are usually Urinary Luteinizing Hormone (uLH) tests. As a result, BBT charts are much less commonly used today than OPKs.
2) Endometrial Biopsy
A specialist takes a sample of the cells lining the uterus (endometrium) after ovulation occurs. They then test the sample to look for signs of inflammation, changes in the endometrium (due to ovulation), and a change in hormones. This test is usually performed about 7 to 12 days after ovulation. Today, this procedure is rarely performed, because it does not help with infertility diagnosis and treatment. Another test, called the Endometrial Receptivity Assay (ERA), requires an endometrial biopsy and is sometimes done to try to determine the best day to transfer an embryo in an IVF cycle. Unfortunately, this test has not been shown to improve pregnancy rates in most women.
3) Testing for Luteinizing Hormone
Ovulation Predictor Kits (OPKs) detect the ovulation-triggering hormone, luteinizing hormone (LH), in the urine. Levels of LH reflect the presence or absence of ovulation. It can help a specialist time diagnostic procedures and inseminations and intercourse. OPKs are generally effective about 90% or more of the time.
4) Testing for Progesterone
A blood test for progesterone can be helpful to confirm ovulation or the level of progesterone in early pregnancy. This test is also commonly performed during an IVF cycle to determine whether or not to proceed with a fresh embryo transfer.
Ultrasonography uses sound waves to image and examine the uterus, ovaries, endometrium and ovarian follicles. The imaging test can be performed via the woman’s abdomen or vagina. The specialist can also use ultrasonography to look for signs of ovulation, which include:
- Smaller follicle size when it collapses after ovulation
- Loss of clear follicles
- Fluid in the follicle sac
- Sufficient thickness of the endometrium
The presence of multiple small follicles may be signs of polycystic ovarian disease.
6) Testing the Health of the Ovaries
Fertility doctors may use a combination of the following tests to check the health of a woman’s ovaries and the ‘supply’ of eggs (ovarian reserve):
- Follicle Stimulating Hormone (FSH) test, a hormone made in the pituitary gland. Levels of FSH increase as the number of eggs decreases. Thus, FSH levels increase with age. Levels are checked between days 2 and 4 of the woman’s menstrual cycle. FSH levels below the range of 10 IU/L are considered normal. FSH levels above 15 IU/L are associated with lower pregnancy rates.
- Estradiol test, a hormone produced by the ovary. Levels are checked between days 2 and 4 of the woman’s menstrual cycle. Levels less than 85 picograms/mL are considered normal. While higher levels can indicate problems in ovulation, many women with a slightly abnormal result will still be able to get pregnant.
- Anti-Mullerian Hormone (AMH) test, which measures this hormone made inside the follicles, can be performed at any time in the menstrual cycle. AMH levels decrease with age since the number of follicles decrease. Levels above 0.9 nanograms/mL are generally considered normal, but women can get pregnant with lower levels.
- Clomiphene Citrate Challenge Test (CCCT): A more sensitive test in which the doctor checks both FSH and estradiol levels between days 2 and 4 of the menstrual cycle. Between days 5 and 9, the woman is then given a 100 mg dose of the fertility drug, clomiphene citrate. FSH levels are also checked, which should be below 10 mIU/mL. The CCCT is a little more sensitive in picking up decreased ovarian reserve than only testing for FSH and estradiol levels alone, but it is indicated in very few patients.
- Ultrasound to determine the number of antral follicles (small follicles) in the ovaries and help diagnose decreased ovarian reserve (DOR). Usually, a woman shows signs of DOR if she has less than a total of 8 antral follicles in both ovaries and the ovaries are less than 3 mL in volume.
It is important to remember that even women who experience a slightly abnormal results will often still be able to get pregnant.
When is Ovarian Testing Performed?
These tests are usually performed if a woman is about 33 years of age or older, or if she has other risk factors, such as:
- a cigarette smoker
- family history of early menopause
- ovarian or extensive pelvic surgery
- signs of premature ovarian failure
- recurrent pregnancy loss
Laparoscopy is a surgical procedure that uses a thin, lighted tube (a laparoscope) to see and examine the uterus, fallopian tubes, ovaries and pelvic surfaces. A common sign of ovulation is the appearance of follicular cysts, which are non-harmful, fluid-filled sacs that appear on the ovaries. Follicular cysts suggest that ovulation is occurring. Laparoscopy can be very helpful in diagnosing infertility in women.
8) Other Female Endocrinology Tests
Testing the levels of other endocrine hormones can help identify the causes of infertility. These may include checking the levels of:
- Thyroid Stimulating Hormone, to help determine diseases of the thyroid gland
- Serum Prolactin (PRL), a hormone normally produced in large amounts during pregnancy but which can interfere with normal ovulation in a woman who is not pregnant
- Androgen hormones, particularly testosterone, which can help detect polycystic ovarian disease, a disorder in which the ovaries are enlarged and contain numerous follicular cysts
Tests for Pelvic Disorders
Your fertility doctor may suspect a problem within the pelvis or the tissue that lines the abdomen, uterus, bladder and rectum (peritoneum). One or more of the following diagnostic tests are likely to be used:
1) Ultrasonography and Sonohysterography
Ultrasonography is an ultrasound-based imaging technique that helps doctors visualize the structure of organs. It is useful in detecting abnormalities in the pelvic region often associated with infertility. For example, ultrasonography can diagnose a condition called hydrosalpinges, in which the fallopian tubes are blocked by scarring (often due to previous pelvic infection). Ultrasound can also diagnose ovarian cysts such as endometriomas, and disorders of the uterus such as fibroids, adenomyosis and uterine developmental abnormalities. Problems in the pelvis and ovaries can also be detected using a similar technique called sonohysterography, which is a special ultrasound technique injecting fluid inside the uterus and fallopian tubes to check the inside of the uterus for abnormalities such as scar tissue, fibroids or polyps (growths attached to the inner wall of the uterus) and whether the tubes are open.
Hysterosalpingogram is a radiology procedure that examines the uterus and fallopian tubes. A radio-opaque fluid is injected into the uterus and fallopian tubes and imaged using x-rays to check the shape of the uterus. look for fibroids, polyps and scar tissue inside the uterus, and whether the tubes are blocked. It is a relatively safe, simple, inexpensive and reliable test, but it can cause cramping in some women.
Hysteroscopy is a minimally invasive procedure in which a fiberoptic ‘telescope’ is passed through the vagina and cervix into the uterus to examine and check for abnormalities. It can be used to find, and also to treat, polyps, fibroids, scar tissue or other abnormalities inside the uterus.
4) Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging is an imaging technique that uses a magnetic field and radio waves to develop pictures of organs inside the body. MRIs can be helpful in some situations, such as identifying and documenting more detail of lesions or other abnormalities inside the pelvis and uterus.
Laparoscopy is an out-patient surgical procedure that uses a thin, lighted tube (a laparoscope) to look for abnormalities inside the pelvis. It can be very helpful to diagnose tubal damage, endometriosis, adhesions, fibroids, uterine abnormalities, ovarian cysts, and other problems. Importantly, most of the conditions that are diagnosed at laparoscopy can be treated at the same time.
Tests Related to the Cervix
Infertility in women is occasionally related to difficulty the sperm has getting from the vagina to the inside of the uterus and fallopian tubes. This can occur because the woman’s cervical mucus (which is a sticky fluid made by the endocervical canal that connects the vagina to the inside of the uterus) may not function normally as a result of surgery or other problems, or that not enough sperm are deposited at the cervix by intercourse at the right time to get pregnant. To determine if there is a problem with the cervical factor as this is called, a fertility doctor may run the following procedures or tests:
1) History of Sexual Intercourse
Your fertility specialist will talk to you about your sexual history with your partner. Questions such as the frequency and timing of intercourse are critical. Intercourse should occur every 1.5 to 2.5 days, starting about 4 to 5 days before expected ovulation. Additional factors such as the type of lubricants that can interfere with sperm, ejaculatory problems and other issues that can affect the delivery of sperm to the cervix at the right time will be explored. This sexual history will also look carefully at your medical history, including: abnormal Pap smears, cervical or vaginal operations, and other surgeries. The lack of high-quality mucus can mean the cervix has problems producing mucus or it may reflect poor timing (of sexual intercourse). Prior surgery of the cervix can also affect cervical mucus production.
2) Tests for Sexually Transmitted Infections
Doctors will test for sexually transmitted infections, such as HIV1, Hepatitis B and Hepatitis C, Syphilis, Chlamydia and Gonorrhea. These tests are mandatory in some States before a fertility doctor can perform Intrauterine Insemination (IUI).
3) Post-Coital Test
A post-coital test analyzes cervical mucus within a few hours of sexual intercourse to inspect the interaction between sperm and cervical mucus. However, in recent years, fertility doctors have stopped using the test. Many studies show it cannot help predict pregnancy. In some situations, the test can at least confirm that the sperm is near the cervix after intercourse.
4) Antisperm Antibody Tests
Sometimes, the woman’s immune system may produce proteins that attack sperm (antisperm antibodies). Doctors can test for these proteins in the man’s sperm. They can also check to see if the partner’s sperm can move through a woman’s cervical mucus to reach the fallopian tubes. However, these tests are now rarely performed because they do not help predict pregnancy. Fertility doctors may run this test if a male has previously undergone a vasectomy.
In addition to taking the male’s medical history and physical examination, the specialist will also test the semen. Semen analysis is the single most important diagnostic test for male infertility. The sperm concentration (number per mL), motility (percent that are moving forward) and strict morphology (shape) and volume are the most important characteristics measured. Causes of male infertility include poor sperm production, blockage in the tubes that carry sperm, infection, genetic abnormalities, lifestyle factors and environmental toxicants.
For infertility patients, preconception genetic testing can help identify any genetic disorders or conditions that may affect their ability to conceive or carry a healthy pregnancy. This testing can also help identify any potential genetic risks that may be passed on to their offspring.
Preconception genetic testing typically involves a consultation with a genetic counselor who, based on medical and family history, will recommend specific genetic tests.
The genetic tests may include carrier screening, which looks for genetic mutations that can be passed on to offspring. This can include testing for conditions such as cystic fibrosis, sickle cell anemia, and Tay-Sachs disease, among others. The couple may also undergo genetic testing to look for chromosomal abnormalities or genetic mutations that can cause infertility or increase the risk of miscarriage.
Preimplantation genetic testing (PGT) is the testing of embryos that are created during an in vitro fertilization (IVF) cycle. PGT-A (for aneuploidy) is done to detect an abnormal number of chromosomes, PGT-M (for monogenic) for gene disorders and PGT-SR (for structural rearrangement) that can increase the risk of miscarriage or abnormal babies. This allows embryos to be screened for specific genetic disorders before they are implanted in the uterus.