The cervical mucus examination of infertile women is an essential step in the infertility evaluation. considering that a cervical factor has been implicated in 5% to 10% of all cases of infertility.^1,2 In facilitating conception. the uterine cervix and its secretions have the following important actions³:

1. Protection of sperm from the hostile environment of the vagina
   
2. Protection of sperm from phagocytosis
   
3. Supplementation of energy requirements of spermatozoa
   
4. Facilitation of sperm transport in the periovulatory period and interference at other times
   
5. Filtration of morphologically abnormal sperm
   
6. Preservation of large numbers of sperm within the cervical crypts and release of sperm into the upper genital tract
   

These conceptive functions and the receptivity' of cervical mucus are determined by its composition. Cervical mucus is composed of several different types of mucus. The three most important ones, as described by Odeblad,⁴ are types E-S, E-L, and G. Types E-S and E-L constitute the ovulatory mucus: type G reflects the stimulation of gestagenic hormones on cervical mucus.^3,4,5

The ovulatory mucus is a mosaic composed of mucus “strings” and “loaves.” The strings (E-S) are fluid gels, and the loaves are more viscid gels (E-L). The result of estrogenic ovulatory stimulation on the mucin components is the production of abundant. watery. thin mucus that is nearly free of cell elements and possesses a high spinnbarkheit and pronounced ferning capacity. The sperm penetrability is highest at this time (Fig. 1). The sperm is found in the fluid (E-S) portion of the mucus, the composition of which allows rapid sperm transport to occur.

Because the cervical factor plays such an important role in infertility evaluations, the clinical post-coital test (PCT) of midcycle cervical mucus is widely accepted. The reasons for this applicability are as follows:

1. It is a qualitative measure of estrogen stimulation.
   
2. It is only by examining the cervical mucus for spermatozoa that any direct information about the adequacy of insemination can be obtained.
   
3. It provides information as to how sperm are interacting with the cervical secretions.
   

This microscopic examination of postcoital mucus has been practiced for more than 100 years. It was originally described by Sims, was modified by Huhner, and still is commonly called the Sims-Huhner test. The PCT has long suffered from inadequate standardization because of differences in variables such as the number of days of abstinence before testing, the time intervals between coitus and the PCT, the methods of collection, and the criteria of normality.

Abstinence Before Testing

The period of abstinence required to obtain the optimal PCT result is debatable, as it is for semen analysis. Some recommend up to 5 days, but most investigators recommend 2 days.^1,2

Time Interval Between Coitus and the Postcoital Test

There have been various recommended time intervals from coitus to the microscopic examination of the cervical mucus. The shortest recorded time interval is 90 seconds,⁶ and the longest is 7 to 8 days.⁷ Clinically, it has been shown that there is a marked decrease in the number of sperm after 24 hours, being negligible after 48 hours.^8,9,10 The decrease becomes clinically apparent after an 8-hour interval. These findings have been substantiated by in vivo sperm transport studies.¹¹ With the use of fractional collection method (see below), the optimal time for collection was 2 1/2 hours after coitus. ¹²

The practical point from this discussion is that any PCT that is normal (i.e.. revealing a large number of motile sperm) can be obtained at 2, 6, 8, or even 12 hours after coitus, allowing some flexibility for the clinician. If, however, the results are abnormal. the test should be repeated at the optimal time of 2 to 3 hours after coitus.

Method of Collection

Difficulties in PCT interpretation have resulted from the different methods of collection used, such as a swab, polyp forceps, and catheters. Davajan and colleagues² attempted to standardize the PCT interpretation by means of a fractional collection method, and I have found it to be very useful. The midcycle cervical mucus is aspirated into a polyethylene suction catheter attached to a large syringe. With a vaginal speculum in place, a wet mount of the vaginal pool is collected and the portio vaginalis cervicis is carefully cleansed with a cotton swab. Then a polyethylene catheter (3 mm in diameter, standard intravenous connecting tubing) is inserted into the endocervical canal. Without allowing contamination by the vaginal contents, the examiner stabilizes the tubing by grasping it 3 cm from the distal end with an atraumatic cervical clamp (large Allis or ring forceps) (Fig. 2). The grip should be adjusted so that the clamp is set at the first ratchet. In that manner the tube is partially, but not totally, occluded. The tube is advanced to the level of the internal cervical os, while gentle suction is applied to the tubing with a 10-mL syringe. The aspiration is stopped, and the grip of the clamp is closed completely. The tubing is gently removed from the endocervical canal, and any remaining mucus at the tip of the tubing is cut with scissors. The spinnbarkheit of the mucus is measured, and the mucus is placed under a coverslip on a slide (Fig. 3). The number of sperm and the percentage of motility are determined by counting five separate fields under high power (×400). The results are recorded on the PCT data sheet (Fig. 4).

It should be mentioned at this point that the PCT as originally described: was a fractional PCT. The polyethylene catheter was divided into three sections corresponding to the internal, mid, and external cervical canal. The internal os count was considered the meaningful determination. It has been shown that this method of testing postcoital cervical mucus is a true reflection of sperm transport in cervical mucus.¹³ Despite the validity of this method of collection, the necessity of fractionalization is debatable. Drake and associates¹⁴ collected 25 specimens in the fractional manner. To check the validity of this method. they interpreted the segments in a blind, random manner. There was a homogeneous distribution of motile and nonmotile sperm throughout the cervical mucus column and therefore no significant difference among the three segments: the use of any portion of the endocervical mucus column would be equally sufficient for PCT interpretation.

Interpretation

Although there is some disagreement concerning the method of PCT collection, there is even more disagreement concerning its interpretation. For some investigators, the mere presence of sperm in the cervical mucus is a normal test; others require 5, 15, or 20 sperm per high-power field. In an attempt to answer the question as to what constitutes a normal PCT, I applied the sperm transport method to the human female reproductive tract.¹¹ Using the fractional collection method: (see Fig. 2), I found the median number of sperm counted to be greater than 15 motile sperm per high-power field;¹³ however, compared with the number of sperm inseminated, the limitations of the PCT are apparent (Table 1). 5 If the PCT is to be used as a measure of semen quantity. then only when there are greater than 15 motile sperm per high-power field can one be assured that the sperm count is at least 20 × 10⁶/mL with 60% motility. A smaller count requires repeated semen analysis.

TABLE 1. Correlative Values of Serum and Cervical Mucus Sperm

It is important to note that a microscopic evaluation of cervical mucus after coitus will reveal a dumping of sperm. This results from the composition of ovulatory cervical mucus (discussed above). Because it is a mosaic of strings containing a fluid gel and loaves containing a more viscid gel, the sperm will lie in the fluid portion of the mucus. Whether or not sperm appears to be dumped on microscopic evaluation will depend on how the slide is prepared: longitudinally or cross-sectionally with the cervical mucus (see Fig. 3; Fig. 5). This emphasizes the importance of viewing multiple microscopic fields. The interpretative values of the PCT are listed in Table 2.

TABLE 2. Postcoital Test

With the basis and method of evaluation for the PCT established. it is important to distinguish the different factors that can be assessed during the clinical evaluation. The first problem to be solved is to distinguish among nonovulatory cervical mucus. altered sperm deposition. altered sperm penetration (sperm defect). and altered sperm transport (mucus defect).

Nonovulatory Cervical Mucus

One of the most prevalent etiologic factors for poor cervical mucus is improper time of collection due to nonovulatory cycles or to incorrect time of the cycle. Ovulation must be documented before the cervical mucus is sampled. and correct interpretations can be based only on preovulatory cervical mucus.² It should be remembered that cervical mucus deficiencies with consequent impedance of sperm penetration are quite frequently the result of nonovulation and insufficient estrogen stimulation. Ovulation can be easily documented by measuring urinary luteinizing hormone (LH) levels collected every morning, and in some situations, in the late afternoon as well. This is determined by a monoclonal antibody technique.^16,17 In addition, the use of ultrasound monitoring to document ovulation has increased the prognostic value of the PCT. ^17,18 Once ovulation is secured, then the other factors can be determined from the PCT.

Altered Sperm Deposition

When the cervical mucus is normal, the PCT can determine difficulties with sperm deposition. Premature ejaculation, hypospadias, oligospermia, azoospermia, decreased semen volume, and impotence are conditions that can be identified. In conditions such as these, there will also be a decreased or absent number of sperm in the vaginal pool. The various etiologic factors must be considered. and once appropriate counseling is accomplished, artificial insemination can be a viable method of conception in many cases.

Homologous insemination (or artificial insemination, husband [AIH]) can be done by intracervical or cup (Milex Products, Chicago, IL) insemination.^1,2 The volume of the semen usually determines the method. If there is only 1 mL or less, intracervical insemination is usually done; a cup is used for larger quantities. It is important that the PCT be repeated after the insemination. Adequate sperm exposure to the cervical mucus should result in a normal PCT after the insemination. From the cervical mucus-sperm transport studies. it has been noted that by 15 minutes the total number of sperm in cervical mucus remains fairly constant for 24 hours: however. a decline in the number of sperm starts 2 1/2 hours after insemination.^11,12 The cervical cup is left in place for 20 to 30 minutes and then removed: the portio vaginalis cervicis is cleansed, and the PCT is performed. Conditions applicable to this form of therapy result in a success rate of 30% to 50%.¹⁹ If the PCT is abnormal after the cervical insemination. intrauterine insemination (IUI) can be performed with washed motile sperm. ^19,20

Altered Sperm Penetration

Poor PCT results often are associated with abnormal semen analysis. Poor motility can be noted when varicoceles and infection are present. If a varicocele is confirmed by physical examination and semen analysis, high ligation of the internal spermatic vein results in an improvement of motility and a 40% to 55% pregnancy rate.²¹

Occasionally, the PCT is abnormal because of sperm immobilization. Nonspecific prostatitis can be treated successfully with trimethoprim-sulfamethoxazole (1 tablet by mouth two times a day for 1 to 2 months) or, if ureaplasma or Chlamydia infection is suspected, with doxycycline (206 mg by mouth the first day, then 100 mg by mouth four times a day for 9 days).²² Although ureaplasma and Chlamydia infections have been proposed as factors contributing to poor PCT, recent studies have found no correlation.^23,24 Immunologic immobilization of sperm in the endocervical canal can occur, but this diagnosis must be confirmed by immunologic tests.^1,2,17,25,26

I also have seen a few instances of poor sperm penetration in patients with grossly normal-appearing cervical mucus. Immunologic test results were negative, but when the pH of the mucus was determined, it was very acidic. In vitro, this mucus can be dialyzed to a normal pH, allowing normal sperm penetration. The activity of the cervical mucus can be improved by an alkaline douche²⁷ or by high-dose estrogen therapy (discussed below).

Altered Cervical Mucus

Preovulatory cervical mucus has the following characteristics: (1) it is thick, opaque, and cellular: (2) it has a poor spinnbarkheit: and (3) it is found in approximately 60% of abnormal PCTs. Repeated cervical bleeding during mucus collection may indicate anatomic defects or cervicitis. Colposcopic examination sometimes reveals a poorly developed endocervical canal with thin, columnar epithelium: this has been successfully treated with cryosurgery. A very cellular cervical mucus often represents cervicitis, which should be treated with antibiotic therapy after appropriate cultures are obtained. If the infection is not resolved by systemic antibiotic therapy, cryosurgery can be employed.

In most of these patients. poor cervical mucus is not secondary to infection but represents a partial or total lack of response of the cervical crypts and glands to estrogen stimulation. The impaired function in these cases may be a late sequela of an inflammatory process or a consequence of surgical procedures such as conization, amputation, or electrocoagulation (loop electrical excision procedure [LEEP]) of the cervix. In many cases, however, no etiology can be determined.

TREATMENT.

Treatment of poor cervical mucus is best accomplished with low-dose estrogen (0.1 mg diethylstilbestrol, 0.625 mg conjugated estrogen. or 50 μg ethinyl estradiol) for the 14 days before ovulation. In a 28-day menstrual cycle, this would be from day I to day 14. There is no advantage to continuing the hormonal therapy during the luteal phase. This treatment markedly improves the quality of cervical mucus in approximately 40% of patients.² After the quality of the cervical mucus is corrected, the PCT should be repeated.

It should be mentioned that in some patients receiving clomiphene (Clomid) therapy there is a persistent antiestrogen effect on the cervical mucus. Once the ovulatory dose of clomiphene is achieved, low-dose estrogen therapy is given for 7 days following the 5 days of clomiphene. Another antiestrogen, tamoxifen (Nolvadex), has been recommended in place of clomiphene for patients in whom clomiphene produces a persistent antiestrogen effect on the cervical mucus.²⁸

In some patients, human menopausal gonadotropin-human chorionic gonadotropin (HMG-HCG) therapy has been successfully used to induce higher endogenous estrogen levels. This results in greater cervical mucus production and is successful, but it requires close monitoring.^{20, 29}

Relative Dysmucorrhea.

Lunenfeld and Insler³ have interpreted these problems as either relative or absolute dysmucorrhea, depending on whether or not the cervical mucus is responsive to high doses of estrogen therapy. respectively. In patients who do not respond to low-dose estrogen therapy, I have used an altered version of their therapy (Fig. 6). as follows:

1. For the first week, ethinyl estradiol (50 μg/day) is given: a PCT is done on day 12 of the cycle.
   
2. The dosage is increased for another week (150 μg/day. and the PCT is repeated. Abundant cervical mucus should be obtained.
   
3. A progestin is then added to accomplish withdrawal bleeding.
   

This cycle is of course lost for conceptive purposes because of the high-dose estrogen therapy. The purpose is to see whether the cervical crypts and glands will respond to this therapy. Lunenfeld and Insler³ originally described this as a diagnostic procedure, but I he found it useful therapeutically. This therapy is successful in a majority of patients. After the one cycle of therapy. the pre-ovulatory cervical mucus is assessed again by PCT during the subsequent spontaneous cycle. Most patients continue to have good cervical mucus production after this therapy cycle. Full scientific evaluation of this therapeutic mode requires the collection of a larger amount of clinical data.

Absolute Dysmucorrhea.

The only therapy available to overcome the barrier of unresponsive thick cervical mucus is IUI.^1,2,19,20 In fact during the past few years, IUI techniques have essentially replaced both estrogen therapy and cervical insemination as a means of treating the cervical factor in infertility.^19,20 A sterile polyethylene tube (No. 16 intercatheter). a Jones in vitro fertilization (IVF) catheter. or a Tefcat catheter (Monoject. Shearwood Medical, St. Louis, MO) attached to a tuberculin syringe is threaded through the cervix. In the past, only 0.2 mL of whole semen was used because a larger quantity could produce an anaphylactic-type reaction and strong uterine contractions. Recently, the use of washed motile sperm instead of whole sperm has been proposed.^2,19,20,31 In performing the IUI, the spermatozoa can be prepared for insemination by different washed sperm and sperm-selection techniques.^2,19,20,31

The importance of cervical mucus as a conduit for sperm migration through the female genital tract is evident. It is essential that the clinician evaluate this factor in the infertility work-up. By initiating a standardized, well-defined postcoital evaluation, one can determine the degree of estrogen stimulation. the adequacy of insemination, and the interaction between male and female secretions. In this manner, different factors can be identified and treatment modalities initiated. While the PCT can provide the above information, it can also be prognostic to an extent^32,33; however, it is mainly a test of performance. Griffith and Grimes³⁴ did not acknowledge the PCT as a test of performance, criticizing it as having poor validity, a lack of standard methodology and established definition of normal, and an unknown rate of reproducibility. Despite these criticisms, the primary role of the PCT is to evaluate the ability of sperm to penetrate the cervical mucus and eventually to migrate to the site of fertilization. Fertilization is not an all-or-nothing phenomenon: In patients with a negative PCT. sperm can be recovered from the peritoneal cavity,³⁵ and fertilization can be achieved with in vitro fertilization.³⁶

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35. Stone SC: Peritoneal recovery of sperm in patients with infertility associated with inadequate cervical mucus. Fertil Steril 40:802. 1982

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