Diagnosing Infertility - Crozer-Keystone Health System - PA

Diagnosing Infertility

The monthly potential for achieving a pregnancy in the average fertile couple having unprotected intercourse is only ~ 25%. This percentage will not increase even if you have intercourse daily and it reflects human fertility potential or fecundity. Over a period of one year, the chance of a successful pregnancy is usually between 80 to 85% so that 7 out of 8 healthy couples will be pregnant within one year. The remaining 15% of the couples failing to conceive are classified as infertile. Infertility is divided into primary and secondary, the former defined as failure to ever achieve pregnancy while the latter denotes a difficulty in achieving pregnancy following a previous success.

The most important influences on fertility are chronological age, frequency of intercourse, duration in which a couple has attempted to achieve a pregnancy and presence of a fertility problem.

When to Seek Medical Advice

If you have been having unprotected sexual intercourse two or three times a week at the time of ovulation, for a year or more and you are not pregnant you meet the definition of being infertile. From the statistical point of view, pregnancy can still occur however, the chances continually decrease with time and you may now want to start thinking about seeking medical assistance.

This definition applies to patients who have “regular” cycles, meaning periods every twenty-three to thirty-five days. Some conditions warrant consultation sooner such as irregular periods, history of previous pelvic surgery or pelvic infections, a history of multiple miscarriages or chronological age greater than 35 years. Male conditions requiring consultation include medical illnesses or infections in the reproductive system and men who do not feel their testes in the scrotum. Remember some commonsense issues need to be evaluated before you seek medical advice concerning your fertility. Body weight, diet and exercise are important influencing factors as well as smoking, alcohol consumption and certain medications. We do know that women who are severely underweight or overweight have difficulties conceiving.

The Infertility Work-Up

On average, the distribution between male and female related infertility is evenly distributed at ~ 40%. Ten percent of the time both partners contribute to the problem and in ~10% of cases the problem is unidentified and is termed unexplained infertility. Before commencing, any testing a detailed history is taken from the couple and a comprehensive physical is performed on the female. Once the work up is complete, a treatment plan is formulated.

Evaluation of the Female Partner

The following tools for assessment must be carefully scheduled according to the menstrual cycle. Please contact the nursing staff should any details need clarification and refer to the baseline testing instructions for cycle day specifics. Essentially the first day of your period is cycle day 1.

Hormonal Studies

Blood tests will be performed during various phases of your menstrual cycle to determine any hormonal imbalances that may affect your fertility. Hormones controlling ovulation, endometrial thickness and implantation will be assessed as well as those that may interfere with these processes. Blood tests assist in diagnosing the cause of your infertility. Analytes measured can include estradiol, progesterone and androgens. Pituitary, thyroid and adrenal function is also assessed in this fashion. The results of the hormone tests usually take two to three weeks.

Endometrial Biopsy

An endometrial biopsy is a microscopic evaluation of the endometrial tissue, which lines the inside walls of the uterus. This test is performed after ovulation to assess the thickness and pattern of the endometrium, which has responded to the estrogen and progesterone produced earlier in the cycle. You must avoid conceiving a pregnancy this cycle as an endometrial biopsy may inflict harm to an early pregnancy. The doctor will insert a speculum inside your vagina and insert a small catheter inside the uterus. You may experience mild cramping and spotting after a piece of the endometrium is sampled. The biopsy is sent to a Pathologist for interpretation. Results will be available in approximately two weeks.


A hysterosalpingogram or (HSG) is a radiological test that evaluates the uterus and patency of the fallopian tubes. Tubal blockage or abnormal growths (polyps, fibroids or scar tissue) can prevent fertilization or implantation. The HSG assesses the anatomy and the potential function of the female reproductive tract. This test is performed directly after the conclusion of your period. The HSG is performed on an outpatient basis in the Radiology Department. A speculum is inserted into the vagina and a special dye is delivered to the uterus through a thin plastic catheter placed in the cervix. The dye should fill the uterus and spill out of the fallopian tubes during which time an x-ray is taken. The patient may experience mild cramping and some spotting during and after the test. Complications may include infection, bleeding and discomfort. Preparation for the test includes a prophylactic antibiotic and over-the-counter pain medicine. Results can usually be determined immediately.

Vaginal Ultrasound

Ultrasound is a diagnostic tool that uses high frequency sound waves to create images of the abdominal organs. The ultrasound is performed vaginally at which time the physician will record images of the ovaries and uterus. Ultrasound may help to diagnose such things as fibroids, pelvic masses, early pregnancy and polycystic ovarian syndrome. Results are usually available immediately.


Hysteroscopy is a minor procedure that may be performed in the physician’s office or operating room and with very little anesthesia in some cases. Hysteroscopy can be used to confirm the results of the HSG such as polyps, fibroids or scar tissue within the uterus. After dilation of your cervix, the hysteroscope is inserted and passed into the uterus. The inside of the uterus is expanded with a solution that is pumped through the scope. This provides visual access the uterine cavity and openings of the fallopian tubes. Patients may experience some cramping and discharge.


A laparoscopy is a short surgical procedure performed on an outpatient basis that allows diagnosis and immediate treatment of certain causes of infertility. Adhesions (scar tissue), endometriosis, tubal blockages and deviations in functional anatomy can be observed. A small fiber optic telescope is placed through a small opening in the naval providing visual access to the ovaries, tubes and uterus. Gas is pumped into the abdominal cavity prior to insertion of the scope. The expansion of the cavity allows the physician to view the reproductive organ more clearly. A tool called a probe is also inserted into the abdomen to lift organs to view hidden areas. Patients may experience fatigue after the procedure and pain in the shoulders or diaphragm.

Antibody Testing

For patients experiencing recurrent miscarriage or repeated pregnancy loss an antibody panel will be run to determine if there is an immune system abnormality.

Evaluation of the Male Partner

Semen Analysis

The parameters of the semen analysis evaluated include the volume, viscosity, concentration (sperm count), motility (the percentage of sperm moving and the progression of the motile), morphology (shape of the sperm) and presence of cellular contaminants such as red or white blood cells. The normal parameters of the sample are as follows:

  • pH: slightly alkaline
  • Volume: > 1.5 ml of semen
  • Concentration: > 15 million/ml
  • Motility: >40% moving (rapid + slow progression)
  • Morphology: >14% normal forms (based upon Kruger criteria)

Additionally, the sample should liquefy in 30 minutes or less. Samples that remain highly viscous may have impaired motility and may be representative of an infection in the prostate. The presence of

some white blood cells in the semen is normal but many white blood cells might indicate the presence of an infection within the urogenital tract.

Abnormalities in any of the semen parameters may compromise the fertility potential of the sample. However, since spermatogenesis occurs in waves, a secondary analysis after 4 to 6 weeks is recommended.

Factors Affecting the Semen Analysis:

Many factors may influence the results of the semen analysis. Since many of which involve specimen transport it is important to adhere to the specimen collection policy defined by the laboratory.

  • Collection technique: Failure to collect the sample by masturbation, failure to collect the entire sample and the use of lubricants may affect results. Additionally, the specimen container itself may not be a friendly environment for sperm; therefore, a laboratory-approved container should only be used during collection.
  • Time of collection: Motility and viability may be compromised in samples that are analyzed more than 1 hour from time of collection. It is important to follow the instruction for transport should you need to collect outside of the facility.
  • Abstinence period: Too short or too lengthy a period of abstinence may affect the concentration or motility of a specimen. It is important to adhere to the guidelines for abstinence as outlined in the specimen collection policy.
  • Recent illness: Recent severe systemic illness in the last three months may affect the semen analysis.
  • Medications: Several medications may affect the results of the analysis.

Semen Cultures

Semen cultures are acquired on some patients when an infection is suspect due to the presence of bacteria or a high concentration of white blood cells.

Fructose Analysis

Fructose analysis is performed on azoospermic samples or samples that are completely absent of sperm. Fructose, a component of the seminal plasma, is necessary for sperm survival and function after ejaculation. The absence of fructose may indicate a blockage in the pathway of ejaculation or in many cases the complete absence of the seminal vesicles and vas deferens, a congenital anomaly afflicting approximately 1% of infertile couples.

Sperm Viability Testing

The sperm viability or sperm survival test provides crude information on the functional potential of the sperm and its ability to survive in vitro for an extended period. If survivability is in normal range, the test may not be very informative. However if sperm survival is poor following the incubation period this has very poor projection on functionality.

Sperm Vitality Testing

Samples demonstrating <30% motility are automatically stained for viability. An immotile sperm may still be viable; therefore, it is important with severely impaired motility, that the percentage of viable sperm be established.

Hormone Analysis

An analysis of pituitary derived hormones such as luteinizing hormone and follicle stimulating hormone can used to determine the pathophysiology of repeated ejaculates demonstrating poor concentration of or complete absence of sperm. Sperm concentration below normal may indicate a problem in the stimulation of the testicle by the brain, via the pituitary gland or an injury to the testicle itself.

Testicular Biopsy

A testicular biopsy is performed to determine whether sperm production exists in the testis. This procedure has particular importance with patients demonstrating a complete absence of sperm. The biopsy is a relatively simple surgical procedure that can be performed under local anesthetic in the physician’s office. If the biopsy reveals that sperm are indeed present in the testicle, then the use of advanced reproductive technology can be utilized in a very successful manner. The most important issues with regard to testicular biopsy include the presence or absence of sperm production and, if present, the stage of development. Maturational arrest, a condition where sperm arrest in their development, has been associated with abnormal hormone concentrations, such as testosterone.


Mastography is another surgical test in which a dye is injected into the vas deferens, the duct through which the sperm travels in order to visualize possible blockages.

Karyotype/Genetic Testing

One of the other tests performed for severely compromised sperm production is a chromosomal analysis (Karyotype). Some men bear an extra chromosome, as in Klinefelter’s syndrome, (47 XXY), which is the reason for the absence of sperm. Congenital bilateral absence of the vas deferens (CBAVD) warrants testing for the gene mutation causing cystic fibrosis. Compromised sperm parameters can also be observed in men carry the CF mutation.

What Are the Most Common Reasons for Male Infertility?

Reduction in any one or more of the semen analysis parameters can significantly reduce the fertility potential of any given specimen. The natural fluctuations in sperm production warrant multiple semen analyses in compromised samples. Many factors can contribute to male infertility, including:


A varicocele is the presence of swollen varicose veins in the scrotum. A varicocele may go unnoticed for a significant period without inducing any chronic aches or pains. It is one of the most common reasons for low sperm motility or the ability of the sperm to demonstrate forward progressive movement. The effects on motility are due to increasing shifts in temperature due to blood accumulation around the testicle.


Blockages of the vas deferens can be observed at birth or may result because of surgery or insult from an accident. Surgical repair can be technically complicated simply due to the size of the vas; however, repair is successful in fifty percent of the cases, meaning that sperm can be identified in the semen after surgery. In the first few months following repair, sperm may be of poor quality but improvements may be seen as time progresses. Secondary to the blockage, sometimes there is damage to the functional lining of the epididymis (the sperm warehouse) because of either infection or increased pressure.

Congenital Bilateral Absence of the Vas Deferens (CBAVD)

For patients born without the vas deferens, the conventional treatment is sperm aspiration directly from epididymis. This is performed by microsurgical techniques in order to find the location of sperm storage.


Following vasectomy, sperm are still produced and stored, but are not released in the ejaculate but rather absorbed. Microsurgical repair of the tube is possible to reverse the effects of the vasectomy. The vasovasostomy is the reversal surgery which is a very delicate procedure, which, in the most skillful hands, can be successful approximately eighty percent of the time.


Many controversies exist with regard to sperm antibody production in the male or in the female tract. We suggest that each case be evaluated on its merit and treated appropriately.

Hormonal imbalance

Hormonal imbalance in the male may follow head injury or result from a tumor in the pituitary gland or in the hypothalamus, the base of the brain. Additionally, since the adrenal is the site where most of the male hormones are produced, malfunction of this gland could have significant impact on male fertility.

Pituitary dysfunction, cirrhosis of the liver, thyroid dysfunction, hyperprolactinemia production and certain enzyme deficiencies influence hormone production in the testes. Mainly, imbalances are due

to improper pituitary stimulation of the testes, which fails to support sperm production. Treatment of hypogonadotropic hypogonadism consists of gonadotropin therapy using human chorionic gonadotropin, luteinizing hormone and follicle stimulating hormone. Although this is a somewhat lengthy and costly therapy, it can be effective in enhancing sperm production.

Substance Abuse

Sustained elevated levels of alcohol can damage the liver and decrease the level of male hormones. Liver cirrhosis and alcohol suppress sperm production directly. Drug abuse can also influence the morphology (shape) and motility of the sperm in a negative fashion. Drug misuse also alters the hormonal balance causing impotence and problems achieving erections.

Undescended Testes

It is common for newborns to demonstrate undescended testes; however, failing to descend from the abdominal cavity to the scrotum by 2 years of age can result in testicular destruction. An undescended testis requires surgical intervention and in some instances, its removal is warranted because of risks of developing cancer.


One of the testicles can undergo torsion, which is described as the twisting around its neck. Damage occurs because of the cessation of blood supply. The signs of torsion are excruciating pain and swelling of the testicle. Once diagnosed, untwisting of the testicle is immediately necessary, since a delay in time will cause permanent functional damage.


Viral infections such as smallpox, mumps and TB have been related to abnormal sperm production. Additionally, gonorrhea, chlamydia, syphilis and other sexually transmitted diseases may influence spermatogenesis or sperm function.


Some medications can play an important role in sperm production and sex drive. These can include drugs for high blood pressure such as Methyldopa, cortico steroids and anabolic steroids for muscle building. Other treatments for Hodgkin’s disease, lymphoma or leukemia, which are called chemotherapeutic agents as well as radiation, can destroy sperm production rendering the man sterile. If the potential for sterility due to surgery, chemotherapeutic or radiation therapy exists, sperm can be banked and stored in our long-term storage facility for as many as ten to twenty years.

Increased Temperature

The testicles are located within the scrotum because the core body temperature can alter sperm production and function. The temperature in the testicle is about 0.8 degrees cooler than in the body. Clothes such as tightly fitting jeans or briefs may cause the testicles to be pressed back into the warmth of the body and when combined with hot tubs, bath and sauna can cause significant

abnormalities in sperm production. Wearing loosely fitting cotton pants and boxer shorts can prevent this damage.

Occupational Hazards

Dangerous chemicals including exposure to heavy metals, nickel, mercury, insecticides, pesticides, benzene, xylene, acids and x-rays can affect sperm production and function. Patients who have experienced exposure to microwave radiation (such as around radar equipment) have a diminished capacity for sperm production.

Ejaculation Problems

Sexual dysfunction can be related to infertility either because of the inability to ejaculate or due to circumstances that make intercourse very difficult. Usually psychological evaluation and treatment of these conditions is both successful and rewarding.

Retrograde Ejaculation

In some cases during ejaculation the semen travels back into the bladder instead of exiting through the penis. One of the most common indicators of retrograde ejaculation is the presence of cloudy urine following intercourse. Patients with this problem usually suffer from diabetes, take medication to control blood pressure or have had prostate surgery, spinal injury or congenital problems. The simplest way to diagnose retrograde ejaculation is to examine the urine following ejaculation. The diagnosis is confirmed if sperm are found in the urine. Extraction of the sperm from the urine is possible. Unfortunately, the recovered sperm are usually of poorer quality and result in diminished pregnancy rates. The combination of IVF with intracytoplasmic sperm injection (ICSI) can provide better results.