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The Treatment of the Cervical Factor in Sterility
The Treatment of the Cervical Factor in Sterility Werner Steinberg, M.D.
with which the cervical factor is regarded today can be explained by the fact that the past ten years have produced better methods of diagnosis and treatment of patients with a negative or unsatisfactory postcoital sperm-migration test. This paper describes the treatment of anatomical defects and the management of physiologic deviations of the cervix, as well as the therapy of endocervicitis in patients with sterility or infertility* problems. THE EVER-INCREASING IMPORTANCE
I: REVIEW OF PREVIOUS THERAPY TREATMENT OF ANATOMIC CHANGES The Infantile Cervix with a "Pinhole Os" Whether an infantile uterus not accompanied by hypogonadism and oligomenorrhea is a cause for sterility has long been a debated question. Williams uses the terms "hypoplastic" and "infantile" uterus synonymously; yet Finkbeiner makes a clear distinction between the two. He defines a hypoplastic uterus as "underdeveloped with otherwise completely normal anatomic build, thus a miniature edition of the normal uterus." Contrariwise, he declares that "the infantile uterus stands midway between the normal and the arcuate one having a three-cornered ( tricuspis) shape thus actually representing the mildest form of a uterine malformation." Both From the Gynecological Service, Newark Beth Israel Hospital, Newark, New Jersey. Received for publication October 17, 1957. * The term "infertility" (from Latin in-fero, I carry or I bear) is used to signify the inability to carry a pregnancy to term, or "habitual abortion." 436
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forms behave differently in their function and the prognosis of treatment is much better in the hypoplastic than in the infantile type. In the former, the aim should be directed toward treating the underlying hypogonadism and establishing regular ovulations and menstruations whereafter a normal cervical mucus may be expected; in the latter, any form of therapy is unsuccessful. Cervical dilatations have long been recommended in the treatment of this condition since they were purported to stimulate the pituitary gland by reflex action; yet Buxton doubts their effectiveness. Different operations, such as Pozzi's "discisio cervicis"16a which have been described to overcome a "pinhole os," have been abandoned today. Intermittent galvanic stimulation was first introduced by Huhner who believed it would stimulate the growth of a hypoplastic uterus. However, the method did not find general acceptance. In congenital hypertrophy of the cervix which represents a minor malformation, the external os becomes visible at the introitus thus making it impossible for sperm.atozoa deposited in the posterior fornix to reach the cervical canal. This condition may or may not be associated with a hypoplastic uterus; however, its rare occurrence is evidenced by the scant literature on the subject. The recommended therapy consists of partial amputation of the cervix, thus leaving enough tissue to assimilate with the normal lengthY
Malpositions of the Cervix Cervical malpositions usually are accompanied by those of the uterus, and their surgical correction has often been advocated to relieve sterility. Bernhard believes them to be a common cause of barrenness having observed "among 653 women with organically caused sterility, malpositions of the uterus in 69 cases (equal to about 10 per cent)." Luque, similarly, thought that "malpositions of the uterus cause sterility in 33 per cent of the women examined," an opinion not shared by Buxton nor by Sturgis. Cervical Lacerations Cervical lacerations sustained during difficult deliveries may cause habitual abortions in subsequent pregnancies, as has been documented in several papers. 26 • 29 Halban 16b wrote: "If the cervical tear extends into the parametrium, a chronic irritation is exerted upon the plexus of Frankenhauser
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which may provoke uterine contractions during early pregnancy." Emmet's trachelorrhaphy will restore the normal anatomic shape of the cervix and obviate premature uterine contractions. However, Te Linde believes that this condition is extremely rare since he has performed "only one such operation during the past 15 years." Cervical Amputation
In 1936, Zoefgen proposed to sterilize women by high amputation of the cervix; he had observed that patients who were thus operated upon during the reproductive years, failed to conceive thereafter. Others, e.g. Graf, refuted the theory on the basis that they had observed pregnancies after cervical amputations. Yet, the postoperative statistics showed that the fertility of such women was definitely lowered, and according to Hollstein, who surveyed 309 cases of cervical amputation, 66 per cent remained sterile and only 34 per cent conceived. For that reason, this operation employed in the treatment of chronic cervicitis has been given up in favor of other methods (see pp. 444-445). The same effect is brought about in the rare cases of cervical agenesis or in the still less frequent occurrence of hypospadias of the cervix, such as recently reported by Seguy and Tchiloyan. The Incompetent Internal Os
This term has been introduced into the American literature by Lash and Lash who consider the syndrome either congenital (in the form of a "diverticulum" of the endocervix) or acquired (after previous forceful curettages, rapid labors, or vaginal hysterotomies). The authors state in their paper: "The literature is devoid of discussion or study of this condition as far as we are aware, particularly in the last twenty-five years." However, Schultze, in 1939, not only described the condition but offered several hysterographic illustrations to substantiate it. He also cites Stoeckel37 who in 1937, spoke of an "ampullary dilatation of the cervix above a stenotic external os which is filled with inspissated cervical secretion." In recent years, this disorder has been dealt with in several publications, here 5 • 22 • 35 and abroad. 3 • 33 Women thus affected are less subject to sterility than to infertility (see footnote on p. 436) and usually abort during the third or fourth month. Lash and Lash have described an operation to correct the condition: They recommend dissecting the underlying mucous membrane from the cervix and
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tightening the internal os with several interrupted catgut sutures. Another approach consists of electrocoagulation of the endocervix by means of highfrequency current, so that the resulting scar formation may produce a narrowing of the internal os. The method of surgical correction in patients with incompetent internal os has been modified in recent years. Barter, Dusbabek, Riva, and Parks (following an idea of Shirodkar) placed a purse-string suture of homologous fascia around the internal os (between vaginal mucosa and cervical musculature) during the twelfth to eighteenth week of pregnancy. In their preliminary report, they obtained good results in a small number of patients. Hall used a heavy nylon suture to occlude an incompetent cervix after previous partial amputation in a woman with habitual abortions and the patient delivered a viable baby. Guttmacher employed heavy black silk as suture material whic!l was threaded through polyethylene tubing; he likewise was able to salvage some pregnancies in women who had experienced three or more miscarriages. Very recently, Baden and Baden reported the delivery of a surviving baby at the thirty-fifth week of gestation, after an incompetent internal os had been repaired ten weeks before.
Cervical Stricture Cervical narrowing with resulting obstruction may be caused by: ( 1) spasticity; ( 2) angulation of the endocervix; ( 3) cicatrization after cauterization. In spite of the different etiology, the treatment recommended in the literature has been almost identical. Cervical dilatations, done in the physician's office, with or without use of an analgesic agent, have been employed for a long time. Stem pessaries, made of hard-rubber or glass, have likewise been a time-honored procedure. Yet, contemporary experts have argued against their use, since they may bring about a previously nonexisting endocervicitis. 40 TREATMENT OF PHYSIOLOGIC CHANGES
Hostile Cervical Mucus Under this heading, the management of patients will be set forth whose cervical mucus exhibits quantitive, physical, or chemical alterations, such as a change of the "threadiness" (Sturgis) or of the "fern-phenomenon," or
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both. That the two conditions do not always occur conjointly was shown in a previous publication. 42 The normal cervix exudes a "cascade-like" mucous thread at the time of ovulation which dips like a wick into the seminal pool. A decreased amount of mucus caused by estrogen deficiency results in a "dry cervix." Since the estrogen level is highest and the quantity of the cervical mucus most abundant at midcycle, the "dry cervix" is caused either by a decreased estrogen production of the ovary or by unresponsiveness of the cervical glands to the hormone. This latter property appears to be constitutional since the secretion of mucus is not augmented by the administration of estrogens. It still is an unanswered question whether orgasm increases the quantity of the cervical mucus, as claimed by Mayer. When patients were asked before taking of a sampling for a sperm-migration test, whether they had experienced an orgasm, only about half gave an affirmative answer; in these, it sometimes was surprising to observe how small an amount of cervical mucus fulfilled its· functional purpose. The treatment of the physically or chemically altered mucus by one of the estrogens was first advocated by Seguy and his co-workers42 and has since been advocated throughout the world literature. The only difference of opinions exists concerning their dosage and route of administration. The naturally occurring steroid may be given as estrone sulfate (by mouth) or as estradiol benzoate (by injection7 ). Synthetic compounds with estrogenic effect have likewise been successfully employed. 15 The only precaution in administering any estrogenic substance is to keep the dose so small that it will not suppress ovulation. TREATMENT OF PATHOLOGIC CONDITIONS
Cervicitis and Endocervicitis The infection of the endocervix by microorganisms is a quite frequent observation and their identification has to precede any treatment. Wet spreads should be taken in the search for Trichomonas vaginalis; a tube containing Nickerson's medium 0 is inoculated with the cervical discharge to test for Candida albicans. If either of them are found present, treatment with any of the trichomonacides or antimonilial agents should be instituted. *Manufactured by Ortho Pharmaceutical Corp., Raritan, N.J.
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Furthermore, after cultures are taken on several mediums to differentiate between the various bacteria, sensitivity tests will bring out the most effective chemotherapeutic or antibiotic agent. It has been shown by different workers 6 • 30 that certain bacteria, if present in the cervical mucus, may become spermicidal and, thus, give rise to a negative sperm-migration test. Therefore, their elimination may bring about a cure of the cervicitis as well as a reversal of the sperm-migration test. To this end, one may follow either a medical or surgical approach.
Surgical Approach. Before Paquelin' s invention of the benzin-cautery, all operations on the cervix were performed with a scalpel; Runner in 1906, was the first one to use the "Paquelin" for cauterization of the cervix. Dickinson introduced the use of the electric "nasal-tip cautery" for treatment of cervical erosions, which still is used extensively. When Hyams described the "cherry-tip electrode" connected to a high-frequency diathermy machine, many workers changed over to the new technic. Cauterization in recent years has been advocated mostly by physicians abroad 8 • 29 • 34 • 36 who attribute a great deal of success to it. Undoubtedly, one obtains an anatomic restitutio ad integrum after any of these procedures, yet a destruction of the cervical glands and, with it, a marked decrease and alteration of the cervical mucus has been observed. Medical Treatment. Caustic agents were the only form of medical treatment of cervical infections until the discovery of the chemotherapeutics in the late thirties and the antibiotics in the forties. Ever since, ahnost all of them have been employed either as vaginal suppositories or creams. Representatives of the sulfonamides are Triple Sulfa Vaginal Cream* or Gantrisin Vaginal Cream f which can be introduced by means of vaginal applicators. However, because of the small number of bacteria which are destroyed by these drugs, the results as to pregnancies achieved were not satisfactory. After the end of World War II, when antibiotics first became available in adequate supply, intramuscular injections of procaine penicillin were first employed by Krohn et al. in the treatment of cervical infections. They found that out of 41 women who sought relief of their sterility, 21 (or 51 per cent) became pregnant; 4 pregnancies ended in spontaneous abortions. Horne * Manufactured by Ortho Pharmaceutical Corporation, Raritan, N. J.
t Manufactured by Hoffmann-LaRoche, Nutley, N. J,
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and Rock employed capsules of Terramycin (Pfizer) by mouth, without previous sensitivity tests; they attained pregnancies in 10 out of 43 women treated (equal to 28 per cent). Later, Kaye and his co-workers reported on the use of the same medication in the treatment of cervical infections. They stressed that the presence of cervicitis irrespective of the type of bacteria, was a cause of sterility, and were able to achieve pregnancies in 20 women out of 55 treated, i.e., a success rate of about 37 per cent. Gepfert and Davis treated 212 patients with suppositories containing "aureomycin HCl, sodium propionate, calcium propionate, stovarsol and beta-lactose"; 90 women became pregnant after having been sterile for one or more years (success rate of about 47 per cent). Tumors
The occurrence of tumors of the cervix as a cause of sterility can be regarded as rare. Most frequently encountered are true cervical or endometrial polyps which have prolapsed through the cervix. Cervical myomas are also comparatively infrequent and usually are accompanied by others located throughout the uterus.
II: RESULTS OBTAINED IN TREATMENT OF THE C£RVICAL FACTOR (119 CASES) ANATOMIC CHANGES
An infantile cervix was encountered 16 times; treatment consisted of negative galvanic current applications and cyclic therapy. The result was very unsatisfactory since only five patients became pregnant (Table 1). Two of these aborted; but it was observed that the uterus had "matured" after the abortion as shown on repeat hysterograms. One patient with congenital hypertrophy of the cervix had a partial amputation of the cervix; although she did not show any other cause for sterility, she never became pregnant. Cervical malpositions were not regarded as a primary cause of sterility and therefore were excluded from the table. Whenever a mobile retrodisplacement was encountered, the insertion of a Smith or Hodge pessary after manual elevation of the uterus sufficed to correct the condition. If the uterus was fixed and could not be elevated, it was the result of either an external endometriosis or a chronic pelvic inflammatory disease. In such
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patients, it is necessary to treat the underlying disease and not the malposition. Five women were encountered who had a "uterine suspension," done elsewhere for relief of sterility, but failed to conceive; a complete sterility study showed that some other factor was responsible. In a previous publication,41 a patient was described who sustained a cervical laceration during her first delivery. Because of four subsequent abortions, Emmet's trachelorrhaphy was performed and the patient delivered a living full-term infant. In all, four such patients were seen, and in three the operation yielded living infants (Table 1). Two patients, after cervical amputations, were observed who exhibited a negative sperm-migration test; both conceived after homologous artificial insemination. Incompet-ence of the internal os was the reason for repeated abortion in four women. A case in point concerned a healthy young woman whose pregnancy on two separate occasions progressed to about the sixteenth week, when the cervix dilated spontaneously (without any noticeable conTABLE 1.
Analysis of 134 Cervical Conditions Encountered in 119 Patients leading to Sterility; 15 Patients Presented Two Conditions
Conditions encountered
Anatomic Changes: Infantile cervix with "pinhole os" Congenital hypertrophy Cervical lacerations Cervical amputation Incompetence of internal os Stenosis or angulation of cervical canal Cicatrization after cauterization Physiologic Variations: Hostile mucus Pathologic Conditions: Cervicitis and endocervicitis Tumors: Polyps Myomas TOTAL
16 1 4a 2 4a 14 4
Pregnancies obtained ( only the :6rst pregnancies are counted)
5 0
sa 2 2a 4 1
19
8
64
27
4 2 134
2 1
55
a These patients showed habitual abortions. The second column contains the number of :6rst living children after treatment.
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tractions); both times spontaneous rupture of the membranes was followed by expulsion of the fetus. She and another such patient were treated by electrocauterization of the endocervix, and both delivered viable babies. On one patient, the Lash operation was tried, but she aborted again. The fourth one was first discovered at 22 weeks gestation and the Shirodkar-Guttmacher operation using a suture of black silk threaded through polyethylene tubing was performed; however, the patient went into labor eight days postoperatively and after the suture was cut she delivered an immature fetus who did not survive. The treatment of the organic cervical stenosis was least successful; out of fourteen patients only four became pregnant. The mode of therapy consisted of repeated dilatations and homologous artificial insemination (Table 1). The same outcome prevailed when the stenosis was due to previous toodeep cauterization; two of these patients were cauterized in the early part of this study, but later this method of treatment was replaced by other forms (seep. 445). PHYSIOLOGIC CHANGES
Hostile mucus as a major cause for sterility was met with 19 times (Table 1) and therefore was the second most frequent condition. Whenever it existed without an accompanying uterine hypoplasia, estrone sulfate ( 0.625 mg. by mouth once daily) from Days 5 to 12 of the cycle was found most efficacious; diethylstilbestrol ( 0.1 mg. once daily) may be substituted. If uterine hypoplasia is the underlying cause for either insufficient or hostile mucus, cyclic medication may be preferable to mere estrogen administration. In either case, parenteral administration of the hormones seems to offer no advantages. PATHOLOGIC CONDITIONS
This group comprises the largest number of patients ( 64) whose methods of therapy are analyzed in Table 2. Only four patients were subjected to cauterization, and when two had developed a cervical stenosis with complete suppression of secretion, the surgical approach was given up and reserved solely for treatment of the postpartum cervical erosion. A toodeeply cauterized endocervix may not only be produced by electric current; chemical caustics (e.g. silver nitrate, trichloracetic acid) may have the .. same result. Sixty patients with cervicitis and/ or. endocervicitis were treated by appli-
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TABLE 2.
445
CERVICAL FACTOR IN STERILITY
Treatment of 64 Patients with Cervicitis Causing Sterility
Treated with
Electrocoagulation Terramycin vaginal tablets Aureomycin vaginal suppositories Intracervical insufHations with the following drugs: Sulfisoxazole ( Gantrisin, Hoffmann-LaRoche) Chloramphenicol ( Chloromycetin, Parke, Davis) Sodium Caprylate ( Caprylium, Strasenburgh) Erythromycin ( Ilotycin, Lilly)
Number of patients
Pregnancies obtained
4 10 16"
2 2 3
34
20
5 6 4
19
" Treatment was started in 28 patients but had to be interrupted in 12 and other drugs used.
cation of some sulfonamide or antibiotic (Table 2). During 1953 and 1954, ten patients were treated with Terramycin Vaginal Tablets (Pfizer), but only two became pregnant. From 1954 to 1955, Aureomycin Vaginal Suppositories ( Lederle) were administered to 28 patients, whose bacteria isolated from cervical cultures showed among others a sensitivity to aureomycin ( 4 plus or 3 plus). Yet, the drug caused allergic manifestations in such a large segment of patients ( 12, equal to about 43 per cent) that treatment had to be prematurely interrupted, to be continued with other medication. Moreover, it was thought that neither vaginal tablets nor suppositories were able to gain sufficient contact with the endocervix, and a different approach of treatment was instituted. When "Ilotycin" (Erythromycin, Lilly)* was introduced as a new "broadspectrum" antibiotic showing comparatively few side-effects, it was felt that intracervical insuffiation of the crystalline powder, usually employed for intravenous injection, would be the most effective form of treatment. The powder was insuffiated into the endocervix by means of a powder-blower ( De Vilbiss No. 175), care being taken to use the smallest possible pressure, lest it pass beyond the uterotubal confines and reach the peritoneal cavity. This treatment was administered during Days 5, 8, and 11 on patients with a regular 28-day cycle, during which time they were instructed to abstain from intercourse. Daily coitus then was recommended on Days 13, 14, and 15. In patients with longer or shorter cycles, the days were adjusted so that treatment ended about three days before the expected ovulation as determined by basal temperature curves. * Dr. R. S. Griffith of the Lilly Laboratories, Indianapolis, Ind., kindly supplied the vials of "Ilotycin" powder.
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As can be seen from Table 2, this form of therapy was the most successful one. Thirty-four patients whose cervical cultures showed micro-organisms sensitive to some chemotherapeutic or antibiotic agents were treated by intracervical insuffiation; 20 pregnancies were obtained. TUMORS There were six patients who exhibited tumors of the cervix, two with polyps and four with myomas. One pedunculated myoma which was "delivered" through the cervical canal was twisted off whereafter the patient became pregnant. SUMMARY The treatment of 119 patients who exhibited a negative sperm-migration test is discussed according to the etiology of the cervical factor causing sterility. . 1. Forty-five women whose cervix presented some anatomic ·deviation (stenosis, angulation, lacerations, incompetence of the internal os) were treated by operative correction or artificial insemination; 17 of them became pregnant. 2. Among 19 patients who showed a "hostile cervical mucus," either alone or in conjunction with some other finding, 8 achieved pregnancy after treatment with small doses of estrone sulfate or diethylstilbestrol; or oral cyclic therapy. 3. Intracervical insuffiation with the chemotherapeutic or antibiotic agent, to which the causative micro-organism proved most sensitive, was the most effective treatment of cervical infections. Out of 34 women so treated, more than half became pregnant. CONCLUSIONS 1. The infantile cervix as part of an underdeveloped uterus responds poorly to any form of treatment; whenever an irreparable deviation from the normal anatomy renders fertilization impossible, homologous artificial insemination is the method of choice. 2. The use of stem pessaries should be avoided as much as possible, since they irritate the endocervix and often bring about an infection of a previously clean cervical canal. 3. Suspension operations to relieve sterility should be performed only
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rarely, unless the retrodisplacement is fixed and caused by endometriosis or chronic pelvic inflammatory disease. 4. Cervical amputation during the reproductive years should be done only exceptionally since it may lower fertility or cause dystocia. 5. The ShiJ:odkar operation, as modified by Guttmacher, is worth while trying, since it offers the only efficacious treatment of an incompetent internal os in preventing repeated abortions. 6. Cauterization or conization in the treatment of endocervical infections causing sterility is warned against because of the resulting destruction of the cervical glands. 35 Gesner St. Linden, New jersey
REFERENCES 1. BADEN, W. F., and BADEN, E. E. Cervical incompetence: Repair during pregnancy. Am./. Obst. & Gynec. 74:241, 1957. 2. BARTER, R. H., DussABEK, J. A., RIVA, H. L., and PARKS, J. Closure of the incompetent cervix during pregnancy. S. Forum. 7:513, 1957 . .'3. BEDRINE, H., and HouLNE, P. Les incontinences du col. Compt. rend. Soc. frant;. gynec. 25:288, 1955. 4. BERNHARD, P. Unfruchtbarkeit des Weibes, in Seitz-Amreich, Biologie und Pathologie des Weibes, Wien, Urban und Schwarzenberg, 1955, Vol. 3, p. 193. 5. BuxTON, C. L. Cervical pathology and sterility problems. Connecticut M. /. 19:864, 1955. 6. BuxTON, C. L., and WoNG, A. S. H. Spermicidal bacteria in the cervix as a cause of sterility. Am./. Obst. & Gynec. 64:628, 1952. 7. CAMPOS DA PAz, A. The crystallization test as a guide to the treatment of cervical hostility. Fertil. & Steril. 4:137, 1953. 8. CHEVALIER, R. M., and MEZZADRA, J. M. Tratamiento quirurgico del cuello uterino en la esterilidad. Proc. First World Congress. Fertil. & Steril., Vol. 1, p. 552, 1953, and discussion. 9. DICKINSON, R. L. Endocervicitis and the nasal cautery tip. Am./. Obst. & Gynec. 2:600, 1921. 10. FINKBEINER, H. Die Bedeutung der Uterusform fiir die Prognose der Sterilitlit. Med. Klin. 50:11:32, 1955. 11. GEFFERT, R., and DAVIS, I. F. Endocervicitis. Its role in infertility. Fertil. & Steril. 4:318, 195.'3. 12. GRAF, A. Die Fertilitlit der Frau nach Amputation und Paquelinisierung der Portio. Monatschr. f. Geburtsh. & Gyniik. 105:272, 1937. 13. GRANJON, A., PHILIPPE, D., and BEAU, A. M. Allongement de hypertrophie du col. Presse m£d. 68:1837, 1955. 14. GuTTMACHER, A. F. Personal communication. 15. GuTTMACHER, A. F., and SHETTLES, L. B. Cyclic changes in cervical mucus, and its practical importance. Human Fertil. 5:4, 1940. 16. HALBAN, J. Gynlikologische Operationslehre ( ed. 2), Wien, Urban & Schwarzenberg. 1947, (a) p . .'331; (b) p. 35.'3.
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17. HALL, H. H. Occlusive trachelorrhaphy for repeated abortion due to cervical incompetence. Am.]. Obst. & Gynec. 71:225, 1956. 18. HoLLSTEIN, K. Ist die Portioamputation eine sterilisierende Operation? Geburtsh. & Frauenh. 11 :554, 1951. 19. HoRNE, H. W., ]R., and RocK, J. Oral Terramycin therapy of chronic endocervicitis in infertile women. Fertil. & Steril. 3:321, 1952. 20. HuHNER, M. Quoted from SIEGLER, S. L. Fertility in Women. Philadelphia, Lippincott, 1944, p. 382. 21. RuNNER, G. L. The treatment of leucorrhea with the actual cautery. ].A.M.A. 46:191, 1906. 22. HuNTER, R. G., and HENRY, G. W. Cervicohysterosalpingography. Fertil. & Steril. 6:68, 1955. 23. HYAMS, M. N. Conization of the uterine cervix. Am. ]. Obst. & Gynec. 25:653, 1933. 24. KAYE, B. M., CoHEN, M. R., and McLEAN, H. Significance of cervical bacteria in infertility. Obst. & Gynec. 3:644, 1954. 25. KROHN, L., HARRIS, J. M., PRIVER, M. S., and FENMORE, M. S. Management of chronic endocervicitis in infertility. Am.]. Obst. & Gynec. 57:774, 1949. 26. KtiHNELT, H. J. Der zervikale Faktor in der Sterilitat. Geburtsh. & Frauenh. 16:651, 1956. 27. LAsH, A. F., and LASH, S. R. Habitual abortion: The incompetent internal os of the cervix. Am./. Obst. & Gynec. 59:68, 1950. 28. LuQUE, F. Papel de los desplazamientos genitales en Ia esterilidad feminina. Proc. First Wild. Congr. Fertil. & Steril., Vol. 2, p. 472, 1953. 29. MARCEL, J. E. Le facteur du col dans Ia sh~rilite feminine. Gynec prat. 7:229, 1956. 30. MATTHEWS, C. S., and BuxTON, C. L. Bacteriology of the cervix in cases of infertility. Fertil. & Steril. 2:45, 1951. 31. MAYER, A. Ober Sterilitat des Weibes als Folge einer Funktionsstorung. Deutsche Med. Wchnschr.61:1425, 1935. 32. PALMER, R. La Sterilite Involontaire. Paris, Masson & Cie, 1950, p. 367. 33. PALMER, R., and LACOMME, M. La beance de I'orifice interne, cause de l'avortment arepetition? Gynec. et Obst. 47:905, 1948. 34. Pous PuGMACIA, L. Cervicitis y esterilidad. Tratamiento por electrocoagulacion. Rev. espan. obst. y ginec. 11:167, 1952. 35. RuBOVITS, F. E., CooPERMAN, N. R., and LAsH, A. F. Habitual abortion: A radiographic technique to demonstrate the incompetent internal os of the cervix. Am. ]. Obst. & Gynec. 66:269, 1953. 36. Ruxz, C. F., and DE LA VEGA, L. La diathermo-coagulaci6n en el tratamiento de la esterilidad cervical. Toko-gin. pract. (Madrid) 13:590, 1954. 37. ScHULTZE, G. F. K. Gyniikologische Rontgendiagnostik. Stuttgart, Ferdinand Enke Verlag, 1939, p. 178. 38. S:EcuY, J., and TcmLOYAN, MLLE. Hypospadias du col uterin. Bull. Fed. Soc. gynec. et obst. 6:268, 1954. 39. SHIRODKAR, V. N. Surgical treatment of habitual abortions, in Modern Trends in Gynecology and Obstetrics, Geneva, Librairie de l'Universite, 1955, p. 545. 40. SIEGLER, S. Fertility in Women. Philadelphia, Lippincott, 1944, p. 383. 41. STEINBERG, W. The importance of cervical lacerations in the management of habitual abortions. ]. Internat. Coll. Surgeons 22:208, 1954. 42. STEINBERG, W. Cervical aspects in sterility and infertility. Fertil. & Steril. 6:169, 1955.
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43. STURGIS, S. H. The cervix and uterus in sterility. Fertil. & Steril. 7:468, 1956. 44. TE LINDE, R. W. Operative Gynecology. Ed. 2, Philadelphia, Lippincott, 1953, p. 381. 45. VIERGIVER, E., and PoMMERENKE, W. T. Measurement of the cyclic variations in the quantity of cervical mucus and its correction with basal temperature. Am. ]. Obst. & Gynec. 48:321, 1944~ 46. WILLIAMS, W. W. Sterility, the Diagnostic Survey of the Infertile Couple. Springfield, Mass., published by the author, 1953, p. 262. 47. ZoEFGEN, W. Sterilisierung durch hohe Cervixamputation. Zentralbl. Gyniik. 60:737, 1936.
with which the cervical factor is regarded today can be explained by the fact that the past ten years have produced better methods of diagnosis and treatment of patients with a negative or unsatisfactory postcoital sperm-migration test. This paper describes the treatment of anatomical defects and the management of physiologic deviations of the cervix, as well as the therapy of endocervicitis in patients with sterility or infertility* problems. THE EVER-INCREASING IMPORTANCE
I: REVIEW OF PREVIOUS THERAPY TREATMENT OF ANATOMIC CHANGES The Infantile Cervix with a "Pinhole Os" Whether an infantile uterus not accompanied by hypogonadism and oligomenorrhea is a cause for sterility has long been a debated question. Williams uses the terms "hypoplastic" and "infantile" uterus synonymously; yet Finkbeiner makes a clear distinction between the two. He defines a hypoplastic uterus as "underdeveloped with otherwise completely normal anatomic build, thus a miniature edition of the normal uterus." Contrariwise, he declares that "the infantile uterus stands midway between the normal and the arcuate one having a three-cornered ( tricuspis) shape thus actually representing the mildest form of a uterine malformation." Both From the Gynecological Service, Newark Beth Israel Hospital, Newark, New Jersey. Received for publication October 17, 1957. * The term "infertility" (from Latin in-fero, I carry or I bear) is used to signify the inability to carry a pregnancy to term, or "habitual abortion." 436
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forms behave differently in their function and the prognosis of treatment is much better in the hypoplastic than in the infantile type. In the former, the aim should be directed toward treating the underlying hypogonadism and establishing regular ovulations and menstruations whereafter a normal cervical mucus may be expected; in the latter, any form of therapy is unsuccessful. Cervical dilatations have long been recommended in the treatment of this condition since they were purported to stimulate the pituitary gland by reflex action; yet Buxton doubts their effectiveness. Different operations, such as Pozzi's "discisio cervicis"16a which have been described to overcome a "pinhole os," have been abandoned today. Intermittent galvanic stimulation was first introduced by Huhner who believed it would stimulate the growth of a hypoplastic uterus. However, the method did not find general acceptance. In congenital hypertrophy of the cervix which represents a minor malformation, the external os becomes visible at the introitus thus making it impossible for sperm.atozoa deposited in the posterior fornix to reach the cervical canal. This condition may or may not be associated with a hypoplastic uterus; however, its rare occurrence is evidenced by the scant literature on the subject. The recommended therapy consists of partial amputation of the cervix, thus leaving enough tissue to assimilate with the normal lengthY
Malpositions of the Cervix Cervical malpositions usually are accompanied by those of the uterus, and their surgical correction has often been advocated to relieve sterility. Bernhard believes them to be a common cause of barrenness having observed "among 653 women with organically caused sterility, malpositions of the uterus in 69 cases (equal to about 10 per cent)." Luque, similarly, thought that "malpositions of the uterus cause sterility in 33 per cent of the women examined," an opinion not shared by Buxton nor by Sturgis. Cervical Lacerations Cervical lacerations sustained during difficult deliveries may cause habitual abortions in subsequent pregnancies, as has been documented in several papers. 26 • 29 Halban 16b wrote: "If the cervical tear extends into the parametrium, a chronic irritation is exerted upon the plexus of Frankenhauser
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which may provoke uterine contractions during early pregnancy." Emmet's trachelorrhaphy will restore the normal anatomic shape of the cervix and obviate premature uterine contractions. However, Te Linde believes that this condition is extremely rare since he has performed "only one such operation during the past 15 years." Cervical Amputation
In 1936, Zoefgen proposed to sterilize women by high amputation of the cervix; he had observed that patients who were thus operated upon during the reproductive years, failed to conceive thereafter. Others, e.g. Graf, refuted the theory on the basis that they had observed pregnancies after cervical amputations. Yet, the postoperative statistics showed that the fertility of such women was definitely lowered, and according to Hollstein, who surveyed 309 cases of cervical amputation, 66 per cent remained sterile and only 34 per cent conceived. For that reason, this operation employed in the treatment of chronic cervicitis has been given up in favor of other methods (see pp. 444-445). The same effect is brought about in the rare cases of cervical agenesis or in the still less frequent occurrence of hypospadias of the cervix, such as recently reported by Seguy and Tchiloyan. The Incompetent Internal Os
This term has been introduced into the American literature by Lash and Lash who consider the syndrome either congenital (in the form of a "diverticulum" of the endocervix) or acquired (after previous forceful curettages, rapid labors, or vaginal hysterotomies). The authors state in their paper: "The literature is devoid of discussion or study of this condition as far as we are aware, particularly in the last twenty-five years." However, Schultze, in 1939, not only described the condition but offered several hysterographic illustrations to substantiate it. He also cites Stoeckel37 who in 1937, spoke of an "ampullary dilatation of the cervix above a stenotic external os which is filled with inspissated cervical secretion." In recent years, this disorder has been dealt with in several publications, here 5 • 22 • 35 and abroad. 3 • 33 Women thus affected are less subject to sterility than to infertility (see footnote on p. 436) and usually abort during the third or fourth month. Lash and Lash have described an operation to correct the condition: They recommend dissecting the underlying mucous membrane from the cervix and
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tightening the internal os with several interrupted catgut sutures. Another approach consists of electrocoagulation of the endocervix by means of highfrequency current, so that the resulting scar formation may produce a narrowing of the internal os. The method of surgical correction in patients with incompetent internal os has been modified in recent years. Barter, Dusbabek, Riva, and Parks (following an idea of Shirodkar) placed a purse-string suture of homologous fascia around the internal os (between vaginal mucosa and cervical musculature) during the twelfth to eighteenth week of pregnancy. In their preliminary report, they obtained good results in a small number of patients. Hall used a heavy nylon suture to occlude an incompetent cervix after previous partial amputation in a woman with habitual abortions and the patient delivered a viable baby. Guttmacher employed heavy black silk as suture material whic!l was threaded through polyethylene tubing; he likewise was able to salvage some pregnancies in women who had experienced three or more miscarriages. Very recently, Baden and Baden reported the delivery of a surviving baby at the thirty-fifth week of gestation, after an incompetent internal os had been repaired ten weeks before.
Cervical Stricture Cervical narrowing with resulting obstruction may be caused by: ( 1) spasticity; ( 2) angulation of the endocervix; ( 3) cicatrization after cauterization. In spite of the different etiology, the treatment recommended in the literature has been almost identical. Cervical dilatations, done in the physician's office, with or without use of an analgesic agent, have been employed for a long time. Stem pessaries, made of hard-rubber or glass, have likewise been a time-honored procedure. Yet, contemporary experts have argued against their use, since they may bring about a previously nonexisting endocervicitis. 40 TREATMENT OF PHYSIOLOGIC CHANGES
Hostile Cervical Mucus Under this heading, the management of patients will be set forth whose cervical mucus exhibits quantitive, physical, or chemical alterations, such as a change of the "threadiness" (Sturgis) or of the "fern-phenomenon," or
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both. That the two conditions do not always occur conjointly was shown in a previous publication. 42 The normal cervix exudes a "cascade-like" mucous thread at the time of ovulation which dips like a wick into the seminal pool. A decreased amount of mucus caused by estrogen deficiency results in a "dry cervix." Since the estrogen level is highest and the quantity of the cervical mucus most abundant at midcycle, the "dry cervix" is caused either by a decreased estrogen production of the ovary or by unresponsiveness of the cervical glands to the hormone. This latter property appears to be constitutional since the secretion of mucus is not augmented by the administration of estrogens. It still is an unanswered question whether orgasm increases the quantity of the cervical mucus, as claimed by Mayer. When patients were asked before taking of a sampling for a sperm-migration test, whether they had experienced an orgasm, only about half gave an affirmative answer; in these, it sometimes was surprising to observe how small an amount of cervical mucus fulfilled its· functional purpose. The treatment of the physically or chemically altered mucus by one of the estrogens was first advocated by Seguy and his co-workers42 and has since been advocated throughout the world literature. The only difference of opinions exists concerning their dosage and route of administration. The naturally occurring steroid may be given as estrone sulfate (by mouth) or as estradiol benzoate (by injection7 ). Synthetic compounds with estrogenic effect have likewise been successfully employed. 15 The only precaution in administering any estrogenic substance is to keep the dose so small that it will not suppress ovulation. TREATMENT OF PATHOLOGIC CONDITIONS
Cervicitis and Endocervicitis The infection of the endocervix by microorganisms is a quite frequent observation and their identification has to precede any treatment. Wet spreads should be taken in the search for Trichomonas vaginalis; a tube containing Nickerson's medium 0 is inoculated with the cervical discharge to test for Candida albicans. If either of them are found present, treatment with any of the trichomonacides or antimonilial agents should be instituted. *Manufactured by Ortho Pharmaceutical Corp., Raritan, N.J.
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Furthermore, after cultures are taken on several mediums to differentiate between the various bacteria, sensitivity tests will bring out the most effective chemotherapeutic or antibiotic agent. It has been shown by different workers 6 • 30 that certain bacteria, if present in the cervical mucus, may become spermicidal and, thus, give rise to a negative sperm-migration test. Therefore, their elimination may bring about a cure of the cervicitis as well as a reversal of the sperm-migration test. To this end, one may follow either a medical or surgical approach.
Surgical Approach. Before Paquelin' s invention of the benzin-cautery, all operations on the cervix were performed with a scalpel; Runner in 1906, was the first one to use the "Paquelin" for cauterization of the cervix. Dickinson introduced the use of the electric "nasal-tip cautery" for treatment of cervical erosions, which still is used extensively. When Hyams described the "cherry-tip electrode" connected to a high-frequency diathermy machine, many workers changed over to the new technic. Cauterization in recent years has been advocated mostly by physicians abroad 8 • 29 • 34 • 36 who attribute a great deal of success to it. Undoubtedly, one obtains an anatomic restitutio ad integrum after any of these procedures, yet a destruction of the cervical glands and, with it, a marked decrease and alteration of the cervical mucus has been observed. Medical Treatment. Caustic agents were the only form of medical treatment of cervical infections until the discovery of the chemotherapeutics in the late thirties and the antibiotics in the forties. Ever since, ahnost all of them have been employed either as vaginal suppositories or creams. Representatives of the sulfonamides are Triple Sulfa Vaginal Cream* or Gantrisin Vaginal Cream f which can be introduced by means of vaginal applicators. However, because of the small number of bacteria which are destroyed by these drugs, the results as to pregnancies achieved were not satisfactory. After the end of World War II, when antibiotics first became available in adequate supply, intramuscular injections of procaine penicillin were first employed by Krohn et al. in the treatment of cervical infections. They found that out of 41 women who sought relief of their sterility, 21 (or 51 per cent) became pregnant; 4 pregnancies ended in spontaneous abortions. Horne * Manufactured by Ortho Pharmaceutical Corporation, Raritan, N. J.
t Manufactured by Hoffmann-LaRoche, Nutley, N. J,
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and Rock employed capsules of Terramycin (Pfizer) by mouth, without previous sensitivity tests; they attained pregnancies in 10 out of 43 women treated (equal to 28 per cent). Later, Kaye and his co-workers reported on the use of the same medication in the treatment of cervical infections. They stressed that the presence of cervicitis irrespective of the type of bacteria, was a cause of sterility, and were able to achieve pregnancies in 20 women out of 55 treated, i.e., a success rate of about 37 per cent. Gepfert and Davis treated 212 patients with suppositories containing "aureomycin HCl, sodium propionate, calcium propionate, stovarsol and beta-lactose"; 90 women became pregnant after having been sterile for one or more years (success rate of about 47 per cent). Tumors
The occurrence of tumors of the cervix as a cause of sterility can be regarded as rare. Most frequently encountered are true cervical or endometrial polyps which have prolapsed through the cervix. Cervical myomas are also comparatively infrequent and usually are accompanied by others located throughout the uterus.
II: RESULTS OBTAINED IN TREATMENT OF THE C£RVICAL FACTOR (119 CASES) ANATOMIC CHANGES
An infantile cervix was encountered 16 times; treatment consisted of negative galvanic current applications and cyclic therapy. The result was very unsatisfactory since only five patients became pregnant (Table 1). Two of these aborted; but it was observed that the uterus had "matured" after the abortion as shown on repeat hysterograms. One patient with congenital hypertrophy of the cervix had a partial amputation of the cervix; although she did not show any other cause for sterility, she never became pregnant. Cervical malpositions were not regarded as a primary cause of sterility and therefore were excluded from the table. Whenever a mobile retrodisplacement was encountered, the insertion of a Smith or Hodge pessary after manual elevation of the uterus sufficed to correct the condition. If the uterus was fixed and could not be elevated, it was the result of either an external endometriosis or a chronic pelvic inflammatory disease. In such
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patients, it is necessary to treat the underlying disease and not the malposition. Five women were encountered who had a "uterine suspension," done elsewhere for relief of sterility, but failed to conceive; a complete sterility study showed that some other factor was responsible. In a previous publication,41 a patient was described who sustained a cervical laceration during her first delivery. Because of four subsequent abortions, Emmet's trachelorrhaphy was performed and the patient delivered a living full-term infant. In all, four such patients were seen, and in three the operation yielded living infants (Table 1). Two patients, after cervical amputations, were observed who exhibited a negative sperm-migration test; both conceived after homologous artificial insemination. Incompet-ence of the internal os was the reason for repeated abortion in four women. A case in point concerned a healthy young woman whose pregnancy on two separate occasions progressed to about the sixteenth week, when the cervix dilated spontaneously (without any noticeable conTABLE 1.
Analysis of 134 Cervical Conditions Encountered in 119 Patients leading to Sterility; 15 Patients Presented Two Conditions
Conditions encountered
Anatomic Changes: Infantile cervix with "pinhole os" Congenital hypertrophy Cervical lacerations Cervical amputation Incompetence of internal os Stenosis or angulation of cervical canal Cicatrization after cauterization Physiologic Variations: Hostile mucus Pathologic Conditions: Cervicitis and endocervicitis Tumors: Polyps Myomas TOTAL
16 1 4a 2 4a 14 4
Pregnancies obtained ( only the :6rst pregnancies are counted)
5 0
sa 2 2a 4 1
19
8
64
27
4 2 134
2 1
55
a These patients showed habitual abortions. The second column contains the number of :6rst living children after treatment.
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tractions); both times spontaneous rupture of the membranes was followed by expulsion of the fetus. She and another such patient were treated by electrocauterization of the endocervix, and both delivered viable babies. On one patient, the Lash operation was tried, but she aborted again. The fourth one was first discovered at 22 weeks gestation and the Shirodkar-Guttmacher operation using a suture of black silk threaded through polyethylene tubing was performed; however, the patient went into labor eight days postoperatively and after the suture was cut she delivered an immature fetus who did not survive. The treatment of the organic cervical stenosis was least successful; out of fourteen patients only four became pregnant. The mode of therapy consisted of repeated dilatations and homologous artificial insemination (Table 1). The same outcome prevailed when the stenosis was due to previous toodeep cauterization; two of these patients were cauterized in the early part of this study, but later this method of treatment was replaced by other forms (seep. 445). PHYSIOLOGIC CHANGES
Hostile mucus as a major cause for sterility was met with 19 times (Table 1) and therefore was the second most frequent condition. Whenever it existed without an accompanying uterine hypoplasia, estrone sulfate ( 0.625 mg. by mouth once daily) from Days 5 to 12 of the cycle was found most efficacious; diethylstilbestrol ( 0.1 mg. once daily) may be substituted. If uterine hypoplasia is the underlying cause for either insufficient or hostile mucus, cyclic medication may be preferable to mere estrogen administration. In either case, parenteral administration of the hormones seems to offer no advantages. PATHOLOGIC CONDITIONS
This group comprises the largest number of patients ( 64) whose methods of therapy are analyzed in Table 2. Only four patients were subjected to cauterization, and when two had developed a cervical stenosis with complete suppression of secretion, the surgical approach was given up and reserved solely for treatment of the postpartum cervical erosion. A toodeeply cauterized endocervix may not only be produced by electric current; chemical caustics (e.g. silver nitrate, trichloracetic acid) may have the .. same result. Sixty patients with cervicitis and/ or. endocervicitis were treated by appli-
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TABLE 2.
445
CERVICAL FACTOR IN STERILITY
Treatment of 64 Patients with Cervicitis Causing Sterility
Treated with
Electrocoagulation Terramycin vaginal tablets Aureomycin vaginal suppositories Intracervical insufHations with the following drugs: Sulfisoxazole ( Gantrisin, Hoffmann-LaRoche) Chloramphenicol ( Chloromycetin, Parke, Davis) Sodium Caprylate ( Caprylium, Strasenburgh) Erythromycin ( Ilotycin, Lilly)
Number of patients
Pregnancies obtained
4 10 16"
2 2 3
34
20
5 6 4
19
" Treatment was started in 28 patients but had to be interrupted in 12 and other drugs used.
cation of some sulfonamide or antibiotic (Table 2). During 1953 and 1954, ten patients were treated with Terramycin Vaginal Tablets (Pfizer), but only two became pregnant. From 1954 to 1955, Aureomycin Vaginal Suppositories ( Lederle) were administered to 28 patients, whose bacteria isolated from cervical cultures showed among others a sensitivity to aureomycin ( 4 plus or 3 plus). Yet, the drug caused allergic manifestations in such a large segment of patients ( 12, equal to about 43 per cent) that treatment had to be prematurely interrupted, to be continued with other medication. Moreover, it was thought that neither vaginal tablets nor suppositories were able to gain sufficient contact with the endocervix, and a different approach of treatment was instituted. When "Ilotycin" (Erythromycin, Lilly)* was introduced as a new "broadspectrum" antibiotic showing comparatively few side-effects, it was felt that intracervical insuffiation of the crystalline powder, usually employed for intravenous injection, would be the most effective form of treatment. The powder was insuffiated into the endocervix by means of a powder-blower ( De Vilbiss No. 175), care being taken to use the smallest possible pressure, lest it pass beyond the uterotubal confines and reach the peritoneal cavity. This treatment was administered during Days 5, 8, and 11 on patients with a regular 28-day cycle, during which time they were instructed to abstain from intercourse. Daily coitus then was recommended on Days 13, 14, and 15. In patients with longer or shorter cycles, the days were adjusted so that treatment ended about three days before the expected ovulation as determined by basal temperature curves. * Dr. R. S. Griffith of the Lilly Laboratories, Indianapolis, Ind., kindly supplied the vials of "Ilotycin" powder.
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As can be seen from Table 2, this form of therapy was the most successful one. Thirty-four patients whose cervical cultures showed micro-organisms sensitive to some chemotherapeutic or antibiotic agents were treated by intracervical insuffiation; 20 pregnancies were obtained. TUMORS There were six patients who exhibited tumors of the cervix, two with polyps and four with myomas. One pedunculated myoma which was "delivered" through the cervical canal was twisted off whereafter the patient became pregnant. SUMMARY The treatment of 119 patients who exhibited a negative sperm-migration test is discussed according to the etiology of the cervical factor causing sterility. . 1. Forty-five women whose cervix presented some anatomic ·deviation (stenosis, angulation, lacerations, incompetence of the internal os) were treated by operative correction or artificial insemination; 17 of them became pregnant. 2. Among 19 patients who showed a "hostile cervical mucus," either alone or in conjunction with some other finding, 8 achieved pregnancy after treatment with small doses of estrone sulfate or diethylstilbestrol; or oral cyclic therapy. 3. Intracervical insuffiation with the chemotherapeutic or antibiotic agent, to which the causative micro-organism proved most sensitive, was the most effective treatment of cervical infections. Out of 34 women so treated, more than half became pregnant. CONCLUSIONS 1. The infantile cervix as part of an underdeveloped uterus responds poorly to any form of treatment; whenever an irreparable deviation from the normal anatomy renders fertilization impossible, homologous artificial insemination is the method of choice. 2. The use of stem pessaries should be avoided as much as possible, since they irritate the endocervix and often bring about an infection of a previously clean cervical canal. 3. Suspension operations to relieve sterility should be performed only
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rarely, unless the retrodisplacement is fixed and caused by endometriosis or chronic pelvic inflammatory disease. 4. Cervical amputation during the reproductive years should be done only exceptionally since it may lower fertility or cause dystocia. 5. The ShiJ:odkar operation, as modified by Guttmacher, is worth while trying, since it offers the only efficacious treatment of an incompetent internal os in preventing repeated abortions. 6. Cauterization or conization in the treatment of endocervical infections causing sterility is warned against because of the resulting destruction of the cervical glands. 35 Gesner St. Linden, New jersey
REFERENCES 1. BADEN, W. F., and BADEN, E. E. Cervical incompetence: Repair during pregnancy. Am./. Obst. & Gynec. 74:241, 1957. 2. BARTER, R. H., DussABEK, J. A., RIVA, H. L., and PARKS, J. Closure of the incompetent cervix during pregnancy. S. Forum. 7:513, 1957 . .'3. BEDRINE, H., and HouLNE, P. Les incontinences du col. Compt. rend. Soc. frant;. gynec. 25:288, 1955. 4. BERNHARD, P. Unfruchtbarkeit des Weibes, in Seitz-Amreich, Biologie und Pathologie des Weibes, Wien, Urban und Schwarzenberg, 1955, Vol. 3, p. 193. 5. BuxTON, C. L. Cervical pathology and sterility problems. Connecticut M. /. 19:864, 1955. 6. BuxTON, C. L., and WoNG, A. S. H. Spermicidal bacteria in the cervix as a cause of sterility. Am./. Obst. & Gynec. 64:628, 1952. 7. CAMPOS DA PAz, A. The crystallization test as a guide to the treatment of cervical hostility. Fertil. & Steril. 4:137, 1953. 8. CHEVALIER, R. M., and MEZZADRA, J. M. Tratamiento quirurgico del cuello uterino en la esterilidad. Proc. First World Congress. Fertil. & Steril., Vol. 1, p. 552, 1953, and discussion. 9. DICKINSON, R. L. Endocervicitis and the nasal cautery tip. Am./. Obst. & Gynec. 2:600, 1921. 10. FINKBEINER, H. Die Bedeutung der Uterusform fiir die Prognose der Sterilitlit. Med. Klin. 50:11:32, 1955. 11. GEFFERT, R., and DAVIS, I. F. Endocervicitis. Its role in infertility. Fertil. & Steril. 4:318, 195.'3. 12. GRAF, A. Die Fertilitlit der Frau nach Amputation und Paquelinisierung der Portio. Monatschr. f. Geburtsh. & Gyniik. 105:272, 1937. 13. GRANJON, A., PHILIPPE, D., and BEAU, A. M. Allongement de hypertrophie du col. Presse m£d. 68:1837, 1955. 14. GuTTMACHER, A. F. Personal communication. 15. GuTTMACHER, A. F., and SHETTLES, L. B. Cyclic changes in cervical mucus, and its practical importance. Human Fertil. 5:4, 1940. 16. HALBAN, J. Gynlikologische Operationslehre ( ed. 2), Wien, Urban & Schwarzenberg. 1947, (a) p . .'331; (b) p. 35.'3.
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17. HALL, H. H. Occlusive trachelorrhaphy for repeated abortion due to cervical incompetence. Am.]. Obst. & Gynec. 71:225, 1956. 18. HoLLSTEIN, K. Ist die Portioamputation eine sterilisierende Operation? Geburtsh. & Frauenh. 11 :554, 1951. 19. HoRNE, H. W., ]R., and RocK, J. Oral Terramycin therapy of chronic endocervicitis in infertile women. Fertil. & Steril. 3:321, 1952. 20. HuHNER, M. Quoted from SIEGLER, S. L. Fertility in Women. Philadelphia, Lippincott, 1944, p. 382. 21. RuNNER, G. L. The treatment of leucorrhea with the actual cautery. ].A.M.A. 46:191, 1906. 22. HuNTER, R. G., and HENRY, G. W. Cervicohysterosalpingography. Fertil. & Steril. 6:68, 1955. 23. HYAMS, M. N. Conization of the uterine cervix. Am. ]. Obst. & Gynec. 25:653, 1933. 24. KAYE, B. M., CoHEN, M. R., and McLEAN, H. Significance of cervical bacteria in infertility. Obst. & Gynec. 3:644, 1954. 25. KROHN, L., HARRIS, J. M., PRIVER, M. S., and FENMORE, M. S. Management of chronic endocervicitis in infertility. Am.]. Obst. & Gynec. 57:774, 1949. 26. KtiHNELT, H. J. Der zervikale Faktor in der Sterilitat. Geburtsh. & Frauenh. 16:651, 1956. 27. LAsH, A. F., and LASH, S. R. Habitual abortion: The incompetent internal os of the cervix. Am./. Obst. & Gynec. 59:68, 1950. 28. LuQUE, F. Papel de los desplazamientos genitales en Ia esterilidad feminina. Proc. First Wild. Congr. Fertil. & Steril., Vol. 2, p. 472, 1953. 29. MARCEL, J. E. Le facteur du col dans Ia sh~rilite feminine. Gynec prat. 7:229, 1956. 30. MATTHEWS, C. S., and BuxTON, C. L. Bacteriology of the cervix in cases of infertility. Fertil. & Steril. 2:45, 1951. 31. MAYER, A. Ober Sterilitat des Weibes als Folge einer Funktionsstorung. Deutsche Med. Wchnschr.61:1425, 1935. 32. PALMER, R. La Sterilite Involontaire. Paris, Masson & Cie, 1950, p. 367. 33. PALMER, R., and LACOMME, M. La beance de I'orifice interne, cause de l'avortment arepetition? Gynec. et Obst. 47:905, 1948. 34. Pous PuGMACIA, L. Cervicitis y esterilidad. Tratamiento por electrocoagulacion. Rev. espan. obst. y ginec. 11:167, 1952. 35. RuBOVITS, F. E., CooPERMAN, N. R., and LAsH, A. F. Habitual abortion: A radiographic technique to demonstrate the incompetent internal os of the cervix. Am. ]. Obst. & Gynec. 66:269, 1953. 36. Ruxz, C. F., and DE LA VEGA, L. La diathermo-coagulaci6n en el tratamiento de la esterilidad cervical. Toko-gin. pract. (Madrid) 13:590, 1954. 37. ScHULTZE, G. F. K. Gyniikologische Rontgendiagnostik. Stuttgart, Ferdinand Enke Verlag, 1939, p. 178. 38. S:EcuY, J., and TcmLOYAN, MLLE. Hypospadias du col uterin. Bull. Fed. Soc. gynec. et obst. 6:268, 1954. 39. SHIRODKAR, V. N. Surgical treatment of habitual abortions, in Modern Trends in Gynecology and Obstetrics, Geneva, Librairie de l'Universite, 1955, p. 545. 40. SIEGLER, S. Fertility in Women. Philadelphia, Lippincott, 1944, p. 383. 41. STEINBERG, W. The importance of cervical lacerations in the management of habitual abortions. ]. Internat. Coll. Surgeons 22:208, 1954. 42. STEINBERG, W. Cervical aspects in sterility and infertility. Fertil. & Steril. 6:169, 1955.
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43. STURGIS, S. H. The cervix and uterus in sterility. Fertil. & Steril. 7:468, 1956. 44. TE LINDE, R. W. Operative Gynecology. Ed. 2, Philadelphia, Lippincott, 1953, p. 381. 45. VIERGIVER, E., and PoMMERENKE, W. T. Measurement of the cyclic variations in the quantity of cervical mucus and its correction with basal temperature. Am. ]. Obst. & Gynec. 48:321, 1944~ 46. WILLIAMS, W. W. Sterility, the Diagnostic Survey of the Infertile Couple. Springfield, Mass., published by the author, 1953, p. 262. 47. ZoEFGEN, W. Sterilisierung durch hohe Cervixamputation. Zentralbl. Gyniik. 60:737, 1936.