Causes of Infertility

You are not alone in your fertility struggles

Approximately 10% of couples have trouble conceiving. A fertile couple has a 20-25% chance of achieving a pregnancy each month. After one year of trying, about 90% of couples who attempt to get pregnant will be successful. The remaining 10% of couples who are unsuccessful after one year are said to have infertility and deserve an evaluation. If a woman is over 35 years of age or has very irregular cycles, the evaluation should be done sooner.

Causes of Infertility

Approximately one third of infertility is due to female factors, one third is due to male factors and one third is due to a combination of female and male factors or is unexplained.

The Basic Infertility Evaluation

Determine if the woman is releasing a healthy egg.

Check if the fallopian tubes are open and the uterine cavity is normal.

Determine if the man's sperm is normal.

Detection of ovulation of a healthy egg

Women are born with all the eggs they will ever have, and at puberty there are about 300,000-500,000 eggs remaining. These eggs are housed in small fluid sacs called follicles in the ovaries. The menstrual cycle begins with a period, which is the lining of the uterus sloughing off. At this time, there is a group of small (<10 millimeter) follicles in the ovaries waiting to grow. Under the influence of follicle stimulating hormone (FSH) from the pituitary gland in the brain, one of these follicles grows and expands with fluid over the next two weeks. The growing follicle makes estrogen which is the hormone that signals the uterus to build up a thickened lining where the embryo will eventually implant. The pituitary gland then uses luteinizing hormone (LH) to signal the mature follicle (about 18-25 millimeters) to rupture (ovulate) and release the egg into the fallopian tube. After ovulation, the ruptured follicle seals back up and forms a cyst called a corpus luteum whose job it is to make progesterone. Progesterone is the signal to the lining of the uterus to be receptive to the implanting embryo. If the embryo does not implant, progesterone levels fall and this causes a period.

(See the picture below for a diagram of these events)

There are several possible reasons for a woman not to ovulate reliably, but sometimes the cause is unknown. One common cause is polycystic ovary syndrome (PCOS) which is characterized by a lack of ovulation, high testosterone and LH levels, weight gain, and resistance to the hormone insulin that controls sugar metabolism. Extreme weight gain, weight loss, stress or exercise can also disrupt the pituitary gland’s ability to send FSH to the ovaries, causing the follicles to not grow or release their eggs. Disorders of other hormones such as thyroid hormone and prolactin can also inhibit ovulation. Finally, menopause occurs when the ovaries run out of eggs, and ovulation cannot occur. Menopause before 40 years old is called premature ovarian failure (POF).

There are several ways to determine if the ovaries are functioning properly. An ultrasound can be done in the first week of the period to count the number of small follicles in the ovaries. This is called an Antral Follicle Count (AFC). Too many small follicles suggests an ovulation problem or PCOS, and too few suggests that the ovary may be slowing down and running low on eggs. An FSH blood test can be done on days 2-4 of the cycle, and if it is high (greater than 10 mIU/mL) it suggests that the ovary will have trouble making follicles. A high FSH indicates a decreased number of healthy eggs (called decreased ovarian reserve) and correlates with a lower chance of pregnancy. If the FSH is very high it indicates potential ovarian failure. Another hormone called AMH is also measured.  AMH is made by the follicles so a higher number for AMH (>1) is associated with a higher ovarian reserve.  A high LH level on days 2-4 suggests the diagnosis of polycystic ovary syndrome. Prediction or confirmation of release of the eggs (ovulation) can be done with ovulation predictor test kits which check for the hormone LH in the urine the day before ovulation, an ultrasound showing a mature (18-25 millimeter) follicle in the ovary, and a high progesterone level (>3 ng/mL) one week after presumed ovulation. A basal body temperature (BBT) chart can be done by recording body temperature each morning on a graph and seeing a rise in the second half of the cycle which is indicative of ovulation. Symptoms of pelvic pain or increased cervical mucus production in the mid-cycle also suggest ovulation.

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Assessment of the fallopian tubes and uterine cavity

The fallopian tubes reach out from the uterus towards the ovaries to catch the eggs with delicate fingers called fimbria. The sperm meet the egg inside the tube and this is where fertilization takes place. The fertilized egg is called an embryo and the fallopian tubes are responsible for gently moving this embryo toward the uterine cavity, while also secreting substances to nurture its growth. The embryo divides from a single cell, to 2 cells and then 4 cells and then 8 cells and so on. By the time it reaches the uterus 4 days later it contains more than 32 cells and is called a morula (a Latin word for mulberry, which it resembles). Once inside the cavity, the embryo further develops into a blastocyst (an embryo with a fluid cavity in the middle) that hatches from a protective shell and then implants into the wall of the uterus.

(See figure below)

It is obvious that the fallopian tubes and uterine cavity are very important for fertility. If the tubes are scarred as a result of infection, previous surgery or endometriosis they may not be able to catch the egg or transport the embryo properly. This could lead to infertility or a tubal (ectopic) pregnancy. If the cavity is distorted by scarring, fibroids, polyps, or a congenital wall called a septum, implantation may not occur properly. These problems may lead to infertility or recurrent miscarriages. One way to evaluate the fallopian tubes and cavity is to inject dye through the cervix into the cavity and out the tubes while doing an X-ray. This test is called a hysterosalpingogram (HSG). Another approach is minimally invasive outpatient surgery where a telescope is placed into the uterine cavity (hysteroscopy) while another scope is placed through the navel to look at the tubes (laparoscopy). During surgery, abnormalities of the cavity or tubes can often be corrected.

Assessment of sperm quantity and quality

Unlike women who are born with all the eggs that they will ever have, men make millions of new sperm in the testicles everyday. The testicles are outside the body to keep them at the slightly lower temperature necessary for normal sperm production. After developing for about 72 days, the sperm are transported to a collecting tube next to the testicle called the epididymis. The sperm are transported up the vas deferens, through the prostate gland, where secretions are added, and out the penis with ejaculation.

It only takes one sperm to fertilize an egg to make a baby, but it takes millions of sperm in the ejaculate to get that one sperm near the egg. This is partly because after intercourse, many sperm are lost in the vagina even before they enter the uterine cavity to swim up through the tube to the egg. They may swim right past the egg or go down the wrong tube or even swim back out of the uterus in the wrong direction. A normal semen sample has 2-5 milliliters (about a teaspoon) of fluid with more than 20 million sperm per milliliter. Of these sperm, at least 50 % should be moving and 5% or more should look perfectly normal. It should be noted that there is tremendous fluctuation in all of these values on a day to day basis for all men, so the semen analysis can show dramatically different results over multiple tests. Also, the semen analysis does not actually evaluate directly how well the sperm can do their job, which is to fertilize an egg. Instead the semen analysis describes characteristics of sperm which estimate their potential to function normally.

The timing of intercourse near ovulation is important because an egg has to be fertilized within 24 hours of release or it dies and the whole cycle is lost. While sperm can live for 3 to 5 days in the uterus and tubes, the highest probability of success occurs with intercourse within a day or two of ovulation. Since sperm are replenished every 2 days or so, it is recommended that couples have intercourse every other day during the fertile time of the cycle.

A history of fathering a previous pregnancy, while certainly encouraging, does not guarantee a normal semen analysis. An abnormal semen analysis may show a low volume of fluid, a low number of sperm, a low number of moving sperm (low motility), a low number of sperm with normal shape, or no sperm at all. In general, abnormalities are due to decreased production of normal sperm or blockages in the sperm exiting the testicles, but many times the cause of an abnormal semen analysis is not known. Factors associated with an abnormal semen analysis include smoking, drug use, excessive alcohol consumption, varicose veins around the testicles, toxic exposures, chemotherapy or radiation, birth with one or both testicles un-descended, significant genital trauma or surgery, infections of the prostate, testicles or epididymis, certain medications, medical diseases such as diabetes or hypertension and some genetic disorders. If no sperm are found in the ejaculate (azospermia), it may be due to a lack of sperm production by the testicles or a blockage or absence of the vas deferens. Genetic conditions can be responsible for azospermia and need to be evaluated. Sperm may still be found in the testicle and can often be retrieved and used in an IVF cycle to create a pregnancy.

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