How common is it?
Infertility in women is ranked the 5th highest serious global disability. About 6% of married women aged 15 to 44 years in the United States are unable to get pregnant after one year of trying. Infertility is defined as not being able to get pregnant after one year or longer of unprotected sex. It can be further divided into:
- Primary infertility: Infertility without any previous pregnancy.
- Secondary infertility: Fertility occurring after having a child in the past.
Time required for conception, approximately 50% of women will be pregnant at 3 months, 75% at 6 months, and more than 85% by 1 year. (Adapted from Barbara LH. ed., (2016). Evaluation of the Infertile Couple. In: Williams gynecology, 3rd ed , pp. 427- 446.)
How is it diagnosed?
Fertility is not just a woman’s problem; both men and women contribute to infertility. In about 35% of couples with infertility, both male and female fertility problems were identified. In about 8% of cases, only the male problem was identified as contributing to the infertility. An infertility evaluation is recommended after 1 year of unprotected sex for women under 35 years or after 6 months for women 35 years and older.
Female Infertility Evaluation:
The evaluations for female infertility fall into two basic categories: ovulatory function and health of the reproductive organs
- Ovulation function is typically evaluated with blood tests to determine if ovulation occurs. A progesterone level >3ng/mL a week prior to expected menses would indicate recent ovulation. Patients can also use over-the-counter ovulation predictor kits to measure urinary luteinizing hormone (LH) concentrations to determine ovulation. As these kits are not 100% accurate, a blood test may be needed to confirm the results. If ovulation is not detected, a further evaluation would be conducted to determine the cause for the lack of ovulation.
- Some women have regular menses but have a reduced response to ovarian stimulation. These patients will need to have their ovarian reserve evaluated. Various ovarian reserve tests are available to provide an indirect assessment of the woman’s ovarian reserve. Day 3 FSH levels and estradiol (E2) levels are commonly used to determine the ovarian reserve. Other tests include clomiphene citrate challenge test (CCCT), anti-mullerian hormone (AMH) level, and antral follicle count (AFC) using transvaginal ultrasound.
Evaluation of the reproductive organs:
The causes of female infertility from anatomic abnormalities are usually in the following areas: ovaries, fallopian tubes, and uterus. Any problems in these organs can cause infertility or difficulty in achieving pregnancy. Examples include obstruction in the fallopian tubes, polyps in the uterus, intrauterine adhesions, endometriosis, and ovarian cysts.
There are several procedures that are used to evaluate the reproductive organs: hysterosalpingogram (HSG), transvaginal sonography (sonohysterography), hysterosalpingo-contrast sonography (HyCoSy), hysteroscopy, and laparoscopy.
Initial evaluations generally involve procedures that are less invasive like HSG, sonohysterography, and HyCoSy. If abnormalities were found during the initial evaluation, more invasive procedures like hysteroscopy, laparoscopy, and MRI would be required for further evaluation.
- Hysterosalpingogram (HSG) is a radiographic tool that evaluates the uterine cavity and the fallopian tubes. This procedure is commonly used to look for abnormalities of the uterus and to look for obstructions or blockages in the fallopian tube. If abnormalities are found during the HSG, further evaluations with more invasive procedures will be required. HSG involves a contrast media that is infused through a catheter from the vagina into the uterus and a fluoroscopy camera. This procedure is minimally invasive and is associated with minimal complications. However, there may be slight discomfort when the catheter is injected and vaginal spotting may occur for a few days after the procedure.
Examples of hysterosalpingogram findings. A. Normal hysterosalpingogram. B. Bilateral hydrosalpinges, distally blocked fallopian tubes filled with serous or clear fluid. (Adapted from Barbara LH. ed., (2016). Evaluation of the Infertile Couple. In: Williams gynecology, 3rd ed , pp. 427- 446.)
- Transvaginal sonography (VS) or sonohysterography uses ultrasound to provide images and assess the reproductive organs. This procedure uses a transducer that is placed in the vagina and a monitor to view the images. The images produced are typically 2D but 3D/4D ultrasound images are also available. Saline can be infused into the uterus to increase the sensitivity and specificity for detecting defects in the lining of the uterus like intrauterine adhesions and polyps and is the preferred procedure for assessing the uterine cavity. When saline is used with sonography, the procedure is called saline infusion sonohysterography. These procedures are simple and well tolerated, although some patients may have some cramping during the procedure.
- Hysterosalpingo-contrast sonography (HyCoSy) is a type of sonohysterography that uses ultrasound and contrast media injected into the uterus through the vagina to provide images of the uterine cavity, fallopian tubes, and the ovaries. This procedure is simple and well tolerated with minimal side effects. Like the saline infused sonohysterography, some patients may have some cramping during the procedure. HyCoSy is commonly used to quickly look for tubal obstructions and assess the uterine cavity.
- Hysteroscopy is an endoscopic evaluation used to examine the uterine environment and is the definitive method for evaluating the uterine cavity. This procedure involves a thin, lighted telescope-like device called a hysteroscope that is inserted and gently moved through the cervix and into the uterus. Hysteroscopy is typically not done during in an initial evaluation and has limitation in evaluating the fallopian tubes and the adjoining structures to the uterus. This is an invasive procedure and may involve anesthesia. Hysteroscopy is a relatively safe procedure but complications such as bleeding, infection, and injury to the reproductive structure can occur.
- Laparoscopy is a direct inspection of the pelvic anatomy using a special instrument called the laparoscope. The laparoscope is a long, slender device with a camera that is inserted into the abdomen through a small incision and the abdominal and pelvic organs are then viewed on an electronic screen. Laparoscopy can be used in patients suspected to have endometriosis or pelvic adhesions. This procedure is not performed during an initial fertility evaluation, as it is invasive and expensive. Some complications that can occur with laparoscopy include bleeding, infection, and damage to the pelvic organs.
The evaluation for potential male infertility concerns mainly with the sperm. As such, the initial evaluation typically consists of collection of semen and basic health assessment. The results of the semen analysis will further guide the evaluation process.
Initial diagnostic tests:
- Semen analysis is the first test done to evaluate male infertility. For this test, the male is asked to refrain from ejaculation for 2 to 3 days before submitting the sample. A semen analysis evaluates the number of sperm, the sperm’s movement, and the shape of the sperm. If the initial semen analysis finds abnormal results, an additional semen sample is requested and analyzed to confirm the initial results. An abnormal result could indicate many different causes including infertility, infection, hormonal imbalance, and genetic defects.
- Hormonal testing is often done in males to detect any hormone abnormalities that may affect sperm production. This is a blood test that typically measures FSH, LH, testosterone, prolactin, and TSH levels.
- The results from the physical examination, semen analysis, hormonal testing, and patient’s medical history will typically be enough to determine the cause of male infertile in most cases. If the cause is still not defined, further evaluation will be done.
Second-level diagnostic tests:
- Genetic assessment. Males with severely decreased sperm counts have a high risk of having genetic abnormalities. Although the low sperm count cannot be corrected, the genetic test will provide information about the status of male health and possible genetic abnormalities their offspring may inherit.
- Bacteriological examination and transrectal/scrotal ultrasound. These tests can identify anatomical abnormalities resulting from chronic inflammation, which usually cause obstruction of the ductal outflow tract. Testicular ultrasonography can be used as a diagnostic tool and is especially useful in patients with an increased risk of cancer.
Third-level diagnostic tests:
- Testicular biopsy. This invasive procedure is done to differentiate testicular failure, whether it is primarily from obstruction or from other causes. Today, testicular biopsy can be considered as both a diagnostic and treatment procedure. Sperm can be obtained from testicular biopsies of males whose semen contains no sperm. The collected sperm would then be used to fertilize an egg in the lab to create an embryo to be implanted into the uterus.
Infertility definitions and terminology. http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ (Assessed 2017–05–12)
Infertility FAQs. https://www.cdc.gov/reproductivehealth/infertility/ (Assessed 2017–05–12)
Grimbizis GF, Solakidis D, Mikos T, et al. A prospective comparison of transvaginal ultrasound, saline infusion sonohysterography, and diagnostic hysteroscopy in the evaluation of endometrial pathology. Fertil Steril. 2010;94(7):2720.
De Hondt A, Peeraer K, Meuleman C, et al. Endometriosis and subfertility treatment: a review. Minerva Ginecol. 2005;57:257.