Pelvic Factor Infertility: Cervical Mucus Abnormalities
It is now widely accepted that sperm move from semen into cervical mucus at their interface as they touch one another during intercourse (via thrusting) or very shortly thereafter. The older belief that the cervix dips into the semen collected in the posterior vaginal vault to allow time for sperm to swim into the mucus is no longer considered likely. This is important clinically since a retroflexed and retroverted uterus (often called a “tipped uterus”) has an anteriorly positioned cervix and this had been thought to be a disadvantage for cervical semen contact. At this time, the relative position of the uterus in the pelvis and the consequent position of the cervix in the vagina is not thought to be very important for fertility.
The pre-ovulatory cervical mucus plays a key role in fertility. The vaginal vault is normally a hostile environment for sperm. Sperm is only comfortable in alkaline (basic) solutions such as semen (with a normal pH of 7.2-7.8). The vaginal vault has a very low pH (acidic) of about 3-4, and sperm typically will not survive in the vagina for more than 1-2 hours. The cervical mucus has a variable pH that depends on the hormonal environment. The hormonal environment is correlated to the time of the menstrual cycle. Cervical mucus is alkalinic (basic) just prior to the time of ovulation when the cervical glands producing the mucus reacts to the predominance of circulating estrogen to make mucus that is
- more abundant,
- more elastic (stretchy),
- less cellular,
- more watery (less thick),
- higher in pH, and
- composed of strands that are aligned to allow greater sperm penetration
If the cervical mucus is “friendly” to sperm then the sperm should be able to survive in the mucus for at least 2 days. This preovulatory mucus acts as a kind of reservoir, from which sperm occasionally move to the fallopian tubes where they normally fertilize an egg. This has led to the popular recommendation to have intercourse (relations, sex) every other day in the midcycle.
I have altered the popular “every other day” advise to recommend daily relations (sex) around the time of ovulation since sperm counts and quality do not appear to be greatly reduced with daily ejaculation (at least when there is no apparent male factor). This seems to provide a greater chance of having fresh healthy sperm available when an egg is released. With less “friendly” mucus, the sperm may not last a full 2 days. If say the sperm only survive for 12 hours then an egg released 13 hours after intercourse would “wait around” for about a day and a half before the next sperm were available (on the every other day intercourse schedule). Since the egg is only fertilizable for 24 hours (about one day), the egg in this example would not result in a pregnancy.
Suboptimal mucus conditions that effect sperm survival and penetration (“hostile mucus”) include:
* (1) very thick and viscous mucus, which limits sperm penetration
* (2) antisperm antibodies (in semen or mucus) such that complement dependent inactivation of sperm within the mucus results in nonmotile sperm or sperm “wiggling in place” within 2 hours of intercourse
* (3) low (acidic) mucus pH, which may inactivate or destroy sperm
* (4) infection within the cervix with inflammatory cells in the mucus digesting the sperm since they are identified as “foreign material”
Although the importance of the cervical mucus for nourishment and the survival of the sperm has been recognized for a long time, there is still no ideal test for mucus quality. The postcoital test is the most popular test. It involves the couple having relations (intercourse) at least 2 hours prior to returning to the office (to allow for complement mediated inactivation of sperm) and in the office the infertility specialist will check the cervical mucus for the presence and number of motile sperm. The test should be completed within 24 hours of intercourse. The World Health Organization has recommended that one consider performing the test 6-10 hours following intercourse to further assess longevity and survival of the sperm.
Despite wide acceptance of the postcoital test, the interpretation and even the method of performing the test have been highly controversial. This test was initially proposed by Dr. Simms in the late 1880s but was not immediately accepted as valuable. Dr. Huhner strongly supported the postcoital test in the early 1910s. Today, the postcoital test is frequently referred to as the Simms-Huhner test. Over the years, the test has undergone considerable modification and a tremendous effort has focused on cervical mucus research. Yet even today the medical community does not have a detailed understanding of the dynamics of cervical mucus as it relates to sperm survival and fertility.
Biochemical and biophysical changes in the cervical mucus in the preovulatory time period are understood as enabling sperm to acquire progressive movement through the cervix so as to gain access to the upper reproductive tract (including the fallopian tubes). These changes in the mucus are apparently a result of the influence of the sex steroids, estrogen and progesterone.
Estrogen generally has a positive effect on cervical mucus with respect to sperm interaction. The effect of estrogen is countered (essentially reversed) by the effect of progesterone. Just prior to the release of the mature egg (ovulation) the estrogen to progesterone ratio is greatest so that the cervical mucus is optimal for sperm. Progesterone production rises rapidly with ovulation to disrupt the beneficial effects of estrogen at the level of the cervical mucus. The mechanism of the beneficial effect of estrogen is complex, involving changes in the architectural arrangement of the mycelles (macromolecular cores that form mucin threads) to create longitudinal channels (tunnels) within the mucus that allow for progressive forward movement of sperm through the cervix. Progesterone results in obliteration of these channels to effectively prevent forward movement of sperm through the cervix.
The method of performing and interpreting the postcoital test varies. I have used a number of techniques in the past, with the most logical to me being the system developed by Dr. Moghessi (a recent past president of the American Society of Reproductive Medicine). This is also the system supported by the World Health Organization (WHO). Essentially, the test provides between 0 and 3 points for each of 5 variables in the evaluation of the mucus with a total of 10 points being considered normal. The test variables involve assessment of
- mucus volume (greater volume gives greater points)
- mucus consistency (less viscous gives greater points)
- ferning (greater fern structures give greater points)
- spinnbarkeit (greater stretch or elasticity gives greater points)
- cellularity (less cells give greater points)
The quality of the cervical mucus is assessed by the score on these variables. The number of motile sperm and their quality of movement (rapid linear progressive, sluggish linear or nonlinear, non progressive, nonmotile) is then assessed. The interpretation of “how many motile sperm” or “what quality of movement” is normal is widely debated due to apparent conflicts within the available literature. These reports include
(1) greater than 25 progressively motile sperm per microscopic high power field (400 x magnification) is normal and is also independently associated with a normal sperm count
2) less than 5 motile sperm per high power field indicates either a decrease in the total motile number of sperm per ejaculate or abnormal cervical mucus
(3) no change in pregnancy rates regardless of the number of sperm identified in the mucus
(4) 20% of known fertile couples tested had 0-1 motile sperm per high power field
(5) 6 of 8 women with abnormal postcoital test results who then underwent laparoscopy 8-36 hours later had motile sperm found in the pelvic fluid (that is motile sperm still made it to and through the fallopian tubes into the fluid behind the uterus)
Abnormal cervical mucus can result from any process that interferes with the function of cervical glands (mucus is produced by these glands). This includes surgery to the cervix with destruction or removal of glands. These surgeries include cryosurgery (freezing), conization (removal of a cone shaped segment) or LEEP (cauterizing loop electrode removal of a segment) of the cervix for an abnormal pap smear.
Treatment of an abnormal postcoital test result is generally placement of sperm above the cervical mucus within the uterine cavity (intrauterine insemination). This effectively will bypass the cervical mucus.
A relatively large group of infertility specialists attempt to correct sperm mucus interaction abnormalities by identifying the apparent problem. In my experience, these efforts have a low rate of success (success being a subsequent normal postcoital test or fertility) and most of my infertility patients are unwilling to wait for months to diagnose, treat and recheck the cervical mucus to document an improvement. Specific treatments that can be considered in an effort to improve poor mucus quality include
(1) viscous thick mucus:
Guiaifenesin by mouth. This is a mucolytic agent that acts to thin out or lyse mucus. It is the active ingredient in Robitussin and some other cold medications that act to thin intranasal mucus (by breaking up the mucus so that it can be expelled)
(2) scanty mucus:
Estrogen preparation by mouth. Premarin in either 0.625 mg or 1.25 mg dosing for 8 to 9 days prior to ovulation may increase the amount of mucus and possibly its quality. This does not generally work in the presence of Clomiphene citrate treatment since the estrogen receptors are blocked.
(3) acidic mucus:
Douching with an alkalinic nontoxic solution such as sodium bicarbonate (1 tablespoon of baking soda into 1 quart of water) to increase the pH of the mucus 30 to 60 minutes prior to intercourse. This has been widely used with mixed success
(4) yellow purulent mucus:
Appropriate antibiotics to treat a presumed or documented infection should be used.
(5) sperm wiggling in place:
Antisperm antibodies are difficult to effectively treat. Steroids may inhibit the immune system in general and production of anti sperm antibodies in particular. These steroids have potentially serious complications and unclear benefit in this context
(6) use of lubricants:
Discontinuation of lubricants, with the possible exception of vegetable oil, is recommended while attempting fertility. Most lubricants including KY jelly and surgilube are toxic to sperm and can interfere with their survival. Astroglide is a commercially available synthetic lubricant that is not associated with known sperm toxicity.