When Sperm Meets Egg Sperm-Mucus Interaction Is the Chemistry Right? "When my doctor did our postcoital test, she said Larry's sperm were dead," Kelly M. told the RESOLVE group. "She also found some white blood cells. She thought one or both of us might have an infection, so she ordered cultures on my cervical mucus and Larry's semen. She also ran some tests to see if we had sperm antibodies," "What did she find out?," the support group leader asked. "Well Larry's sperm survived in donor mucus. And donor sperm survived in my mucus.'' "Then what was killing Larry's sperm in your mucus?'' a woman asked. "The cultures didn't show infection, so she said it was antibodies," Kelly M. said. ."My doctor told me that I was rejecting Larry's sperm just like I might reject a kidney transplant." "What can you do about it?" her friend asked. "Several things", Kelly answered. "First, we want to try washing Larry's sperm and using intrauterine insemination. If we can get around my mucus, we may be able to get around the antibody problem." Kelly and Larry M. belong to a special group of infertile couples whose problem we are just beginning to understand and resolve. I'm very excited about the fertility research taking place in the field of immunology. Antibodies, however, are only one reason why cervical mucus may be hostile to sperm. Other mucus problems may also impair their journey to the egg. Cervical Mucus: Protector and Pathway Acting as the gateway between the vagina and the uterus, the cervix secretes a thick, impermeable mucus to plug the canal. Normally this "hostile" mucus protects the woman's reproductive tract from invading organisms and foreign particles. At the time of ovulation, however, the mucus transforms into a "friendly" path through which sperm can travel in safety. Under the influence of estrogen the thick and sticky mucus becomes clear and stringy. Like lanes in an Olympic swimming pool, tiny tubular paths form to guide the sperm toward the uterus. When the mucus fails to become "friendly" as it does with 5 to 10 percent of all infertile women, the sperm cannot safely begin their journey toward the egg. The hostile mucus, as it is called, will either block the sperm's passage or will damage the sperm so severely that they can no longer function. The aim of fertility treatment is to restore the quality of the mucus so it can: Facilitate or interfere with sperm transport at appropriate times of the month Protect the sperm from the acidic vaginal environment Preserve the sperm in the cervical canal and release them in a steady stream over a period of time Filter out abnormal sperm Protect the sperm from white blood cells which may destroy them as they would invading microorganisms Provide nutrients to the sperm Prevent bacterial contamination of the uterus Performing the Postcoital Test The postcoital test is the primary tool for diagnosing cervical mucus problems. Performed at the time of ovulation, it assesses mucus quality. When I examine the cervical mucus approximately 8 to 12 hours after intercourse, I look for three things: If the husband delivered good quantities of sperm to the cervix If the sperm are swimming vigorously through the mucus If white blood cells are present, indicating an infection in either partner If the results of the test are good, I don't worry about the mucus being a fertility problem. If the results are poor, I know that a mucus interaction problem exists or that the test was performed at the wrong time in the cycle (the most common reason for a poor postcoital test). The best way to insure that the test is performed at the correct time is to plan intercourse with a urine LH test kit. Since we can predict ovulation more accurately than we could when only the BBT chart was available, we are less likely to get poor results from poor timing. A number of factors can cause an abnormal postcoital test: Infection in either partner (indicated by white blood cells in the mucus) Sperm antibodies produced by either partner will cause the sperm to die, to agglutinate (clump together), and/or to shake. Abnormal mucus quality: High-viscosity and/or low-volume mucus can block sperm. Abnormal semen: Sperm antibodies produced by the man as well as infections in the man can adversely affect test results, as can a low sperm count and poor motility. Poor coital technique or ejaculation disorders can also prevent the sperm from reaching the cervix. Infections: Diagnosis and Treatment Diagnosis Infectious organisms in either partner may kill or maim sperm. I suspect an infection if I find dead sperm, white blood cells, and/or cellular debris in the postcoital specimen. Specific microorganisms can often be identified by performing a culture of the cervical mucus but, often I more it more cost effective to initially treat each couple with a short course of antibiotics. In the presence of white blood cells, however, I may prescribe an antibiotic even if the culture comes back negative. Treatment Both partners must be treated to ensure that they are not passing the disease back and forth. The semen and mucus cultures for Dan and Marie C., for example, revealed the presence of chlamydia. I prescribed an antibiotic (doxycycline) for both of them. To avoid exposing an early pregnancy to antibiotics, Marie took the medication during the ten days following the start of her menses. If I continued to find white blood cells in Marie's mucus, I would try to isolate the problem. To make sure Dan was not depositing white blood cells with his sperm, I would ask them to abstain from sex until just before their next postcoital. A normal semen analysis and the presence of the white blood cells only immediately following intercourse would tell me Marie was producing them in response to Dan's semen, which could indicate a sperm antibody problem. I was relieved when I found Marie's mucus free of white blood cells after antibiotic therapy. If treating an infection with antibiotics restores a normal post coital test, up to 42 percent of the couples treated will conceive within three months, and 84 percent within one year. Testing for Sperm Antibodies The Sperm-Mucus Cross Tests Normally antibodies attack foreign substances invading your body. For some unknown reason, however, 4 percent of all men produce antibodies against their own sperm. (The incidence of this autoimmunity increases from 4 percent to 50 to 60 percent in men with vasectomies. The sperm antibodies are probably a protective mechanism to help get rid of millions of unused, trapped sperm.) The effects of antisperm antibodies will usually show up in the semen analysis: the sperm may clump together (agglutinate) or shake in random motions. Sperm antibodies are also found in the cervical mucus of 30 percent of women with unexplained infertility problems. If a fairly recent semen analysis shows that unexposed sperm have normal forward motility, but the postcoital test shows them shaking or clumping, I'll suspect that the woman is the source of the sperm antibodies. A sperm-mucus cross test will help me understand the exact nature of a couple's sperm antibody problem. John and Leslie P. were referred to me after four years of unexplained infertility. John's semen analysis was normal and their cultures were negative. When their family doctor did a postcoital, however, he found dead sperm. Since they used a urinary LH test kit to predict ovulation, I knew they had timed the test perfectly. The couple obviously had a sperm-mucus interaction problem. If I suspect an antibody problem, I can order special tests to look for antibodies in the woman's blood, cervical mucus, and attached to sperm using an immunobead sperm test. Treatment for Antisperm Antibodies Intrauterine Insemination (IUI) When the sperm from the man are antibody-bound, they can achieve only a 15.3 percent pregnancy rate. Sometimes, though, we can reduce the adverse effects of the antibodies by having the man ejaculate into a nutrient liquid, washing the semen from the sperm and using them for intrauterine insemination. When washing restores function to more than half of the sperm, we can achieve a 66.7 percent pregnancy rate. IUI may also be helpful for women producing sperm antibodies. This is what John and Leslie P. decided to try. By washing John's sperm and injecting them directly into Leslie's uterus, we gave his sperm a head start against her hostile mucus. I cautioned them, however, that since Leslie's antibodies could be anywhere in her genital tract, IUI might not work. Moreover, women with sperm antibodies are twice as likely to have a spontaneous abortion. If IUI didn't work, they might want to consider in vitro fertilization. Although a sensitive pregnancy test showed a pregnancy after the second insemination, Leslie's period started a week later. I was sorry to tell them that she had probably aborted. They were not discouraged; in fact, they were elated. Now they knew that John's sperm could swim to her egg and fertilize it. Undaunted, they continued with IUI two months later Leslie's period was late again. We didn't know whether or not to celebrate because she wasn't out of the woods yet-and wouldn't be for a few months. We all sighed a breath of relief when she entered her second trimester with Mom and baby doing well-Dad too. Now they have a red-haired, green-eyed baby girl who's made them forget they ever had a fertility problem. Condom Therapy Use of condoms during intercourse for a prolonged period of time may reduce the level of the woman's antibodies to the extent that the sperm will not be affected. The woman must avoid all contact with the man's sperm for three to six months; this includes oral sex as well as skin contact. (If the man is producing antibodies to his own sperm, however, condom therapy will not work.) Many people do not want to go this time-consuming route and will elect to use IUI instead. This method was more popular prior to availability of IUI and has fallen out of favor because it is less successful. High-Dose Steroid Therapy Experimental therapy with high-dose steroids for men with antisperm antibodies appears to produce a 30 to 40 percent pregnancy rate. Although few studies have been done with women producing sperm antibodies, steroid therapy may prove to be more effective than condom therapy. In addition, suppressing the antibodies may diminish the spontaneous-abortion risk. However, this therapy is not without risk. High dose steroids result in loss of calcium from the bones. There have been cases reported where steroids used to treat infertility have resulted in hip fractures requiring hip replacement surgery. At this time, I fell that the risk of this therapy is too great to warrant its routine use. In Vitro Fertilization By washing antibodies from the sperm and fertilizing the woman's egg outside her body through in vitro, we can avoid exposure to antibodies in the semen and in the mucus. Before attempting in vitro fertilization, a hamster penetration test should be performed on the man's sperm to ensure that once they are treated they will be able to fertilize an egg. Since sperm antibodies produced by the man or woman are associated with a high spontaneous-abortion rate (50 percent), many couples may wish to try IAIH first. IAIH is much less demanding on the couple and quite a bit less expensive More research is needed before in vitro can be considered a viable option for resolving sperm antibody problems. Poor Mucus Quality Mucus viscosity and volume abnormalities may be caused by surgical procedures performed on the cervix, by in utero DES exposure, and by clomiphene citrate ovulation induction treatment. About 40 percent of the time a low-dose estrogen supplement will improve mucus volume and viscosity. However, I generally recommend IUI to bypass the mucus problem as the result is more predictable. Women suffering from cervical stenosis (scars sealing the cervix) may respond to gradual dilation and estrogen therapy. Ejaculation Disturbances or Poor Coital Technique When the semen is poor or when the coital technique does not provide an adequate supply of sperm to the cervix, the postcoital test may appear abnormal, even though neither of these abnormalities represents a sperm mucus interaction problem. Artificial insemination with the husband's sperm and/or counseling on coital techniques may be helpful in overcoming these problems. Immediately before ejaculation, a muscle at the opening to the bladder constricts so that sperm rushing from the ejaculatory ducts are forced out through the penis and not back into the bladder. Occasionally diabetics or men with neurologic disorders and men who have undergone prostate surgery may have difficulty constricting that muscle. At the time of ejaculation, the semen spurts into the bladder rather than out the penis. I will suspect this if the amount of semen is very low. I can check for this by testing a urine sample immediately after ejaculation. If I find sperm in the urine, I know retrograde ejaculation is the problem. Although urine is normally toxic, we can often collect a good sperm sample for intrauterine insemination by draining the bladder and instilling a small amount of nutrient media into the bladder. I will ask the man to empty his bladder immediately after ejaculation and will often retrieve healthy sperm for insemination. When coupled with ovulation induction medication, intrauterine insemination can often be successful. If this fails, a specimen can be retrieved as mentioned above and used for in vitro fertilization or intracytoplasmic sperm injection. But more about that in Chapter 21. The sperm's journey from your vagina to the egg through your fallopian tube is fraught with peril. Only a hundred or so will survive to encounter this precious genetic package, provided your egg can pass into and through your fallopian tube. Unfortunately tubal problems are the most common cause of infertility. In the next chapter you'll learn what can cause tubal problems and what you can do to correct them. Click here to read Chapter 16, Sperm-Egg Transport: Solving Tubal Problems or go to the Miracle Babies Online Table of Contents For more information on your initial visit to your physician read the INCIID Routine Fertility Workup or IVF.com Homepage. Miracle Babies and Other Happy Endings for Couples with Fertility Problems Copyright © 1986 Mark Perloe M.D., and Linda Gail Christie. Return to the IVF Homepage This page, and all contents, are Copyright © 2005 by IVF.com, Atlanta, GA, USA.