Finding the Cause for Your Infertility

Male Evaluation                Female Evaluation
Semen Analysis       Post Coital Test (PCT)
      Ovarian reserve tests
      FSH
      LH
      Estradiol
      Anti Müllerian Hormone (AMH)
      Inhibin-B
      Clomiphene Citrate Challenge test (CCCT)
      Antral Follicle Count (AFC)
      Prolactin
      TSH
      Ovulation assessment
      Ultrasound
      Progesterone level
      Endometrial biopsy
      Hysterosalpingogram (HSG)
      Saline Infusion Sonography (SIS)
      Diagnostic surgery
      Laparoscopy
      Hysteroscopy
     

So you’ve decided it's time to see a fertility specialist. What should you expect?


The Medical History

  • Bring your husband or partner along when meeting with your doctor for the first time.
  • Make sure to bring along with you any records of previous treatment, surgery reports or laboratory results.
  • Let your doctor know if you take any medications or have any allergies.
  • The doctor will then review your medical, menstrual, sexual, and life-style history. Occupational factors, diet, caffeine, smoking and alcohol use, exercise and stress will be carefully reviewed as they may all contribute to your infertility.  

The Physical Examination

Your doctor will perform a complete physical examination which may also include a pelvic ultrasound to see if there is any problem with the uterus or ovaries. 


The "Fertility Evaluation"

After your doctor completes the physical examination he will discuss with you his impression and recommend a number of tests.  This is known as the “Fertility Evaluation”. Keep in mind that there may be several factors contributing to your infertility and a complete evaluation is necessary before initiating treatment. The entire fertility evaluation can be completed within one cycle and consists of:

  • Semen Analysis to make sure that there is not a problem with your partner’s sperm.
  • Ovarian Reserve Tests
  • Hysterosalpingogram (HSG) or tubal x-rays to rule out tubal or uterine problems.
  • Ovulation Assessment  

MALE EVALUATION 

 

The Semen Analysis


  

In this test, freshly ejaculated semen is examined under the microscope to evaluate the number and quality of sperm and several other characteristics of the semen.

  • Count (the number of sperm): sperm concentration is the number of sperm per milliliter. Average concentration is about 60 million per milliliter. A sperm concentration of over 20 million per milliliter is considered normal.
  • Motility (the percentage of moving sperm). Motility is considered normal when at least 50% of observed sperm, show good forward movement. These are the strongest sperm, swimming fast in a straight line (Grade 4). Some of the sperm may be moving slower in a circle or in crooked lines (Grade 3). Other sperm move their tail but have no forward motion (Grade 2) or fail to move at all (Grade 1). 
  • Morphology (the size and shape of the sperm). Morphology is considered normal if 14% or more of the observed sperm have normal shape.
  • Volume - greater than 2.0 milliliters is considered normal. A low volume may reflect complete or partial blockage of gland secretions contributing to the seminal fluid. If the volume is less than 1 milliliter, the semen may not be in close enough proximity to the cervix to allow sufficient sperm to swim up to the uterus and fallopian tube.
  • White cells – Their presence in the semen may indicate an infection. A semen culture is typically ordered. If the culture is positive for bacterial infection, antibiotic treatment for the husband and a repeat semen analysis usually follow.
  • PH level – normal pH range is 7.2 – 8.0.  Too little or too much acid in the semen is detrimental to the sperm
  • Liquefaction - It normally takes less than 20 minutes for semen to change from a thick gel into a liquid. An unusually long liquefaction time may indicate an infection.
  • Fructose level – absence of fructose in the semen may indicate blockage of the seminal vesicles which secrete a significant amount of the fluid of the ejaculate.

THE FEMALE EVALUATION


Ovarian reserve tests - most of the tests are done on day 3 of the menstrual cycle

  • Follicle Stimulating Hormone (FSH) level. FSH is an important hormone that regulates the development of your eggs.  In general, if you are under age 40, a FSH level less than 10 indicates good quality of eggs. A high level of FSH suggests that there is a reduction in both the number and quality of eggs remaining in your ovaries. However, the most reliable indicator of egg quality, is your age. If you are 44 years old and you have a normal FSH level, you can not assume that the quality of your eggs is good. In fact, your chance of conceiving with IVF is only 2%. Likewise, young women with a mildly elevated FSH level may have fewer eggs remaining but their egg quality may still be good with reasonable IVF pregnancy rates. High FSH levels are typically seen in older women, women with history of ovarian surgery, chemotherapy, radiation or endometriosis. Generally speaking FSH levels lower that 10 miu/ml are reassuring, while FSH levels in the 12-15 miu/ml range indicate lower egg quality and poorer IVF success rates. Women with FSH levels higher than 20 miu/ml rarely benefit from treatment utilizing their own eggs and they should be advised to consider donor egg IVF.
  • Estradiol (E2) level. High estrogen levels on day 3 of mestrual the cycle indicate diminished ovarian reserve (DOR) even if the FSH level is completely normal. It is very important to measure both day 3 FSH and estrogen (E2) levels because high levels of either one is equally predictive of a decrease in both the number and quality of the eggs. Ideally, day 3 estrogen levels should be less than 50 pg/ml. Day 3 estrogen level greater than 100pg/ml is considered abnormal.
  • Clomiphene Citrate Challenge Test (CCCT) – This test is used to predict poor ovarian reserve in women whose day 3 FSH level is still normal. The test is performed as follows:
    • Day 3 of cycle – blood test to measure FSH and estradiol levels.
    • Clomiphene (100 mg) is given on days 5-9 of the cycle.
    • FSH level is repeated on day 10 of the cycle.

The Clomiphene Citrate Challenge test is considered abnormal if the FSH level on either day 3 or day 10 is greater than 12 or if the day 3 estradiol level is greater than 100. The test has not been universally accepted because the CCT appears to have no advantage over a simple cycle day 3 FSH level when evaluating the ovarian reserve.


  • Antral Follicle Count (AFC) – This is an ultrasound examination performed between days 2-4 of the menstrual cycle to determine the number of antral follicles (small immature eggs) present within the ovary. Low numbers of antral follicles (less than 4) suggest of diminished ovarian reserve and may correlate with a poorer IVF outcome. 
  • Inhibin-B level - This hormone level, measured on day 3 of the menstrual cycle, is decreased in women with poor ovarian reserve. Several studies suggest that a low day 3 serum inhibin-B may be indicative of a poorer response to ovulation induction as compared with women who exibit a high day 3 inhibin-B. Many centers, however, do not order this test because abnormal values have not been clearly established.
  • Antimullerian Hormone (AMH) level. Studies have demonstrated a gradual decrease in AMH levels as a woman gets older. This decline has been attributed to a decreasing number of eggs within the ovary. A low level of AMH suggests that the ovary may be depleted of eggs, and is predictive of low egg production (poor response) during In Vitro Fertilization (IVF).

Other hormone testing

  • Prolactinan elevated prolactin (over 100ng/ml) can indicate a benign pituitary tumor (adenoma) or prolactinoma. Pituitary MRI will be necessary to make a diagnosis and monitor treatment. Elevated levels of prolactin can interfere with the ovulation process and may require treatment with a prolactin lowering medication such as Bromocriptine (Parlodel) and cabergoline (Dostinex). High prolactin level is seen in women with Polycystic Ovary Syndrome  (PCOS). Other causes of high prolactin include hypothyroidism (low thyroid), pregnancy and medications such as tranquilizers and anti hypertensive agents.
  • TSH (thyroid stimulating hormone)an elevated TSH level indicates that your thyroid gland may be underactive. This condition can cause the prolactin level to rise, preventing ovulation. Although controversial, some experts believe that the TSH level should be no higher than 2 and they recommend taking thyroid supplement to keep it within normal range. 

The Post Coital Test (PCT)

A “post-coital test" helps your doctor evaluate the interaction between the sperm and the cervical mucus. You may be asked to use a urinary kit to detect ovulation (LH surge) and to come to the office several hours after intercourse for the test. A small amount of mucus is removed from the cervix and tested for consistency. The mucus is then placed on a slide and examined under the microscope for the presence of sperm, inflammatory cells and bacteria. Some of the mucus obtained can be sent to a laboratory for culture to rule out pelvic infections, such as Chlamydia or Ureaplasma, which may cause tubal disease and miscarriages.


Assessment of ovulation

  • Ultrasound – Utilized to measure the thickness of the lining (endometrium) of the uterus and the size of the follicles containing the eggs (oocytes). When ready for ovulation the follicles should measure between 16-20mm (below, right) and the uterine lining should be thicker than 8mm (straight yellow line).
  • Progesterone level A single blood progesterone level, measured seven days after ovulation, can help determine whether or not ovulation is the problem. A progesterone level over 15 is an indication of a normal ovulatory process.
  • Endometrial biopsy is sometimes performed 12 days after ovulation. The endometrial biopsy involves taking a small sample of the lining of the uterus (endometrium) to see if it is developed sufficiently to allow a fertilized egg to implant.

 Imaging tests

The Hysterosalpingogram (HSG)

A hysterosalpingogram  or HSG is an x-ray procedure performed to determine whether the fallopian tubes are open and to see if the shape of the uterine cavity is normal. It is an outpatient procedure that takes less than 10 minutes to perform. It is done after menses have ended, but before ovulation (between days 5-9 of cycle).


How is a Hysterosalpingogram done?

During the procedure, you will be positioned under a fluoroscope (a real-time x-ray imager) on a table. The doctor will place a speculum in the vagina and cleanse the cervix with antiseptic solution. Local anesthetic may be given to make the procedure more comfortable. A catheter device (cannula) or a small inflatable balloon will be inserted through the opening of the cervix. The uterus is gently filled with liquid containing iodine (contrast). The contrast then enters the tubes, outlining their length. If the tubes are open, the dye will spill out of their ends. Any abnormalities in the uterine cavity or fallopian tubes will be visible on a monitor. The HSG is not designed to evaluate the ovaries or diagnose endometriosis. The hysterosalpingogram may reveal tubal blockage, uterine fibroids or polyps, uterine anomalies or scar tissue within the uterine cavity.


What is a normal HSG?


The uterine cavity is normal and both tubes are open. Note the contrast fluid (dye) delineating the thin tubes extending from the uterus. The "cloudy" appearance at the end of the tubes indicates that dye has spilled out of the tubes, and that they are open.


What is Saline Infusion Sonography (SIS)?



In this test, saline is injected into the uterus while performing vaginal ultrasound to make sure that there are no uterine abnormalities (fibroids, polyps, scar tissue or uterine malformations) which may cause infertility, bleeding, or pain. The top left picture demonstrates a normal test. The dark area, outlined in yellow, is the saline filling the uterine cavity and no abnormalities are seen. The top right ultrasound image demonstrates an abnormal uterine cavity with an irregular border caused by an endometrial polyp (outlined in red and marked by white arrow). The test takes only a few minutes to complete and is associated with little discomfort, if any.


Diagnostic Surgery


Laparoscopy  and Hysteroscopy  are not routinely done during fertility evaluation. Your doctor may recommend the procedures if there are symptoms suggestive of endometriosis  or if you had an abnormal HSG  suggestive of tubal blockage, uterine polyps, fibroids  or adhesions (Asherman’s syndrome). Occasionally, laparoscopy is also utilized for treating polycystic ovary syndrome (PCOS) by ovarian drilling.

In summary, there are various reasons for infertility - 40% percent of the time there may be a problem with the man’s sperm, and problems with fallopian tubes or uterus in another 35%. In 15% of the couples the problem can be traced to ovulation problems and in another 10%-15%, no obvious cause can be identified (unexplained infertility).

Having completed all these tests, there is about a 90% probability that your doctor will be able to pinpoint the cause of your infertility. Once this is done, you can proceed to treatment and, hopefully, a successful outcome.

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