Current Reviews: Fallopian Tubes in Sterility

Current Reviews WILLIS

E.

BROWN,

editor-in-charge

Fallopian Tubes in Sterility Perspective The fallopian tubes or oviducts are unique structures in human female reproduction. They have long been considered the most important single area of infertility. Approximately 35 per cent of all infertile marriages are now known to be due to abnormalities within these structures. This review of the role of the fallopian tubes in infertility will follow the outline below.

Outline I. II. III. IV.

Considerations on the anatomy and function of the fallopian tubes Importance of the tubes in infertility Research studies Clinical studies A. Anatomic tests and their hazards: Uterotubal insufflation, radiography, other tests; hazards of tests B. Physiologic tests: Rubin test, Speck test, oil, starch, etc. C. Partial or temporary closure: Spasmodic, physiologic, inflammatory, endocrine V. Tuberculous salpingitis VI. Therapy A. Psychologic B. Medical: Antibiotics, spasmolytic drugs, oil, gas, estrogens C. Surgical: Reconstruction following ectopic pregnancy, polyethylene tubing, reimplantation, salpingolysis, refertilization, Estes operation VII. Summary and clinical application

ANATOMY AND FUNCTION Through the fallopian tube the ovum is conducted into the uterus and the spermatozoa ascend the generative tract for fertilization of the ovum. It is in the 178

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central portion of the fallopian tube that fertilization takes place and the creation of the embryo is accomplished. Thus any abnormality which distorts the anatomy or the physiology of the fallopian tube may result in infertility. During recent years many clinical and research studies have been conducted on the fallopian tube to delineate both its anatomic and physiologic functions. Clinical tests have been devised for the measurement of both these functions, and the literature contains many excellent descriptions and reviews of these methods of study and their clinical importance. It is at once apparent that mechanical obstruction may be formed by various adhesive blocking reactions to endosalpingitis, or may come as a result of perisalpingeal adhesions and kinking. Obstruction of the tube also may result from endometriosis and other intrapelvic inflammatory reactions. Physiologic disorders of the tube are of a different nature. They may come as a result of endocrine disturbances which change the ciliary and peristaltic action of the tube, or they may be caused by emotional factors. Changes in the secretory action of the epithelial cells lining the tube may so alter the environment of the spermatozoa, ova, or the growing embryo as to preclude normal development and the preparation for nidation in the uterine cavity. These two basic types of disorders have been studied both clinically and in the research laboratory. Reports on experimentation, on both humans and animals, give much information which is useful in the study of the infertile couple. This "Current Review" will be centered on these anatomic and physiologic disorders and the clinical and laboratory tests for measuring these deviations of clinical importance in the diagnosis and management of infertility.

IMPORTANCE IN STERILITY Recent studies on infertile couples and infertile matings have revealed various distributions of problems. In these the fallopian tube ranks high, accounting for approximately 60 per cent of the factors of infertility. Tubal pathology in infertility is doubly important-not only because of its high frequency but also because of the frequency of incorrect diagnosis. Jeffcoate 1 found that at least 43 of 116 negative insufRation tests and 13 of 86 negative salpingograms were erroneous. It is, therefore, of utmost importance to determine with precision whether or not the tube is damaged in its anatomic relationships, in its functional relationships, or in both, and to what extent the damage is amenable to medical or surgical therapy. Success in handling infertility of tubal origin is perhaps in direct relation to the precision of the diagnostic accomplishments. Fortunately there are available various tests and diagnostic procedures to delineate these disorders. Errors in omission and commission result in some instances in heroic but unsuccessful surgical attempts, and in others in the development of pregnancies when the tubes had appeared completely and permanently closed.

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RESEARCH STUDIES Physiology

In the past few years many observations have been made of the mechanism by which the ovum gains entrance into the ampullary end of the oviduct. Hartman 1A showed that as ovulation approaches in the rabbit the fimbriae of the tube moved conSiderably. Similar observations have been made on the hen. Westman2 observed that the blood-filled fimbriae in both rabbit and monkey expand over the ovary in such a manner that the lateral surfaces of the ovary present themselves to the tube. Blandau's2A observation of the rabbit indicated that the fimbriated end of the tube regularly engulfs the ovary at the time of ovulation, greatly enhancing the entrance of the ovum into the fimbriated end of the tube. Stange3 describes a muscular organ known as the muscle attrahens which moves the tube towards the ovary at the time of ovulation. In part, these observations have been confirmed in the human by Doyle,4 who, utilizing the culdoscope, has observed the migration of the ovum, as he believes, by simple flotation and siphonage into the fimbriated end. He also observed the tube grasp the ovary with a type of suction which appeared to facilitate the passage of the ovum from the follicle and into the ampullary end of the tube. These phYSiologic observations tend to support the belief that the tube plays an important part in effecting the entrance of the ovum into this structure. Anatomy Several specialized studies have been made on the anatomy of the tube which might facilitate the function described above. Detailed anatomic studies reported by Herrlingkoffer;5 Lisa, Gioia, and Rubin;6 Stange;3 and others show a series of spiral muscle bundles progressing obliquely throughout the length of the tube. Longitudinal and circular muscle fibers which assist in the peristaltic function also seem to be present. The anatomic demonstration of a uterotubal sphincter has not been complete. Blanchard;6A Lisa, Gioia, and Rubin;6 Herrlingkoffer;5 and others have been unable to demonstrate an anatomic uterotubal sphincter. Several authors have studied the epithelial lining of the tube. Endometrial or endometrium-like tissue was found in the interstitial and terminal portions of the tube. It is believed by Lisa, Gioia, and Rubin 6 to be one of the factors involved in ectopic gestation. The epithelium of the infundibular and ampullary portion of the tube is somewhat variable in Blanchard's6A description. It varies from that of uterine epithelium at the cornual end to cuboidal epithelium in some areas. De Paepe's7 studies on the tube have demonstrated that the nodular thickenings found in the tube are primarily small diverticula, sometimes of an inflammatory type and sometimes due or similar to endometriosis. It is his opinion that these lesions are not congenital. Siegler 8 found similar diverticula which he was able to demonstrate preoperatively by salpingography.

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The epithelial function of the tube as a receptor or chemical environment for the spermatozoa, ova, and fertilization has been studied by Chang. 9 He finds that the spermatozoa must be in the tube a minimum of 6 hours before actual fertilization occurs. Toni and MaccaferrFo studied the microscopic size and frequency of muscle cells in women of different ages. They noticed a considerable change from the age of 60 onward, presumably the declining years of reproductive function.

Critique These studies on the anatomy and physiology of the tube have been of great help in evaluating the role of this structure in fertility. It is now apparent that the tube plays an important part besides being a conduit and that an intact coordinated muscular function is necessary for the ovum to gain entrance into the tube. Not only must the tube move to surround the ovum, but peristalsis and suction are necessary also to carry the ovum into the tubal canal. There is suggestive evidence that integrated hormonal influence is necessary to prepare the proper chemical environment for preparation of the spermatozoa for fertilization.

CLINICAL STUDIES Anatomic Tests

Clinical studies concerning the role the tube plays in infertility have slowly assumed scientific respectability. While a great variety of diagnostic procedures have been advocated, in general they can be divided into two basic technics, anatomic and physiologic. The Rubin test, with its kymographic recording of peristalsis, is a combined anatomic and functional test. After Rubin l l showed the ability to demonstrate tubal patency clinically by introducing carbon dioxide through the uterotubal tract, a vast number of reports appeared endorsing the Rubin test as the simplest and most satisfactory for tubal patency. A second general method for the demonstration of anatomical tubal patency is radiography. Because of the irritative processes associated with iodized oil, many comparative studies have been made to test newer agents with the established technics. As with any clinical technic, errors in mechanics or in judgment will result in inaccurate information. White 12 devised a series of checks to safeguard against error in both technic and interpretation. Among the errors in technics she mentions are omission of preliminary x-ray films of the pelvis; failure to test for the patency of the cannula prior to use; selection of improper media; failure to alter the position of a markedly angulated corpus uteri; failure to avoid great pressures; failure to inject an adequate amount of medium; failure to take sufficient clinical observations (films or auscultation); and failure of follow-up examination. Careful attention to these and other details of the procedures will greatly minimize errors in judgment.

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Comparison of Technics Many authors have attempted to compare the value and medical complications of several methods. JeHcoate,1 comparing salpingograms and insufHation tests, found that both carried a significant degree error in determining tubal patency. Pelvic inflammation occurred in 1 per cent of his 1023 cases and was slightly more common after hysterosalpingography. Campos da Paz 13 in a study of partial tubal obstruction emphasized the advantages of both uterotubal insufHation and hysterosalpingography. Both procedures carried a high incidence of failure to detect this type of pathology. Similar discrepancies in and complementary data on these two procedures are recorded by Keryell,14 Zenisek,15 Mackey,16 Vogt,17 and others. All authors concur with the discussion in my 1953-54 Year Book17A in which I stated that the competition between these two procedures is unwarranted; that each has its own special field of usefulness and both are important. Bendick,18 in a simplified and relatively inexpensive sterility study program, has advocated the use of fluoroscopy.

Evaluation of Radiopaque Media A variety of new water-soluble agents have been introduced to avoid complications of oil-soluble media. Freeth19 reports using Viskiosol-6 in 100 patients with satisfactory results. Jackson20 employed Ethiodan in 104 salpingographies and was impressed with the freedom from granulomatous and inflammatory reactions. Hiibscher21 praises Joduron-S. Rubin, Myller, and Hartman22 report their favorable experience with Salpix. Roland, Carpenter, and Rich23 discuss a new watersoluble medium, Medopaque-H. They, too, find some advantage in the combined hysterosalpingography and insufHation procedure. Palmer and Pulsford24 attempt to compare the iodine concentration of the polyvinyl alcohols in 10% and 35% concentrations. They feel that the increased viscosity of the polyvinyl carrier oHers some advantages in radiographic detail over the aqueous solutions and avoids the complications caused by the oil-soluble agent. From these observations it is obvious that the hazards of hysterosalpingography by oil infusion are established and of clinical Significance. Miiller25 describes infusion of oil into the pelvic veins and damage to tube wall by the irritating quality of these agents. Similar results are reported by Zacharias;26 Bergman, Norman, and Sjostedt;27 Aaron and Levine;28 and others. They all describe systemic and local irritative reactions, the formation of granulomas, and other similar reactions to trapped or persistent iodized oil which further complicate the care of the infertile patient. Palmer29 describes his experience with a modified form of Lipiodol-F prepared in an ethyl-alcohol ester. This new combination reduces the solution's viscosity and in 200 hysterosalpingographies produced no toxic manifestations or pelvic peritoneal irritation.

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These many studies of the effectiveness of the several nonoily agents confirm the earlier reports by Brown and Jennings30 and appear definitely to have established a trend in contrast media. The introduction of the several polyvinyl alcohol vehicles and the modification of the Lipiodol base to an alcohol ester all confirm the rising objections to the use of oil-soluble iodized substances.

Use of Antibiotics Because of the high incidence in inflammatory disease, several investigators have advocated the use of antibiotics. Ryden and Westgren 31 have added penicillin to their opaque media and imply that streptomycin may be used in combination or alone. Similar recommendations are made by other authors.

Other Tests of Tubal Patency As additional tests for tubal patency, several ingenious methods have come forward. Speck introduced a test for the retrograde transtubal insufBation of a phenolsulfonphthalein which can be absorbed from the peritoneal cavity and appears in the urine in a short interval. Davis, Ward, and King 32 have reviewed this test in 110 women and found it 85 per cent accurate. The errors were about equally divided between false-positive and false-negative tests. However, its extreme simplicity renders it of some value as a preliminary screening device. Herstein33 and others have pointed out the advantages of direct visualization by the culdoscope or retrograde injection of several dyes. Although these technics delineate tubal patency, they seem to introduce sufficient additional hazards to limit their wide application.

Critique Thus it becomes apparent that tubal patency can be demonstrated either by uterotubal insufBation of several gaseous agents or by radiographic technics employing the fluoroscope or film. Each of these has certain distinct advantages in demonstrating tubal patency, and in many instances the two procedures are complementary. In some cases they are combined; simultaneous employment offers speCific benefits. While tubal patency can be demonstrated by uterotubal insufHation, it and these other tests fail to show anatomic derangement of partial tubal patency or alterations in the lumen or in fertility. The hazard of iodized-oil insufHation appears to be greater than with the aqueous, gaseous, or macromolecular media in these patients.

Physiologic Tests In attempting to determine the physiologic function of the tube numerous modifications of older procedures have been developed. The refinements in the kymographic recording of Rubin have been restudied. Stabile35 raises a doubt as to the significance of oscillations, recording typical

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tubal tracings after bilateral salpingectomy. These tracings were obtained by the use of an intrauterine balloon placed near the cornua of the uterine cavity. Rubin,l1 in an extensive series of communications, further outlines the advantages he sees in the kymographic recording of the uterotubal insufflation. In his opinion, it is not only a valuable method of determining tubal patency, but clearly demonstrates data which cannot be obtained by hysterosalpingography technics. Its freedom from inflammatory reaction is again stressed. By careful study of the kymographic record, tubal spasms, partial obstruction, and the functional state of the tube can be determined. Rubin further outlines well-documented experiments of extirpated animal organs and those of human beings, indicating that the recorded oscillations are definitely of uterotubal origin. He describes visual observations of peristaltic waves within the tubes seen at laparotomy during uterotubal insufflation. To further study the role of tubal physiology in infertility, several resourceful devices have been developed. Sheffery34 describes a method by which a colored solution is injected into the cervical canal. If a colored fluid is aspirated from the cul-de-sac, tubal patency is established. Then olive oil is introduced into the cul-de-sac and its presence sought in the cervix in 3-4 days. Such oily substances found within the cervical mucus are not only evidence of tubal patency but, more important, also indicate the capacity of the tube to pick up these materials and by peristalsis and Ciliary action bring them through the uterine cavity into the cervix. Decker and Decker~6 have described a similar procedure of depositing starch granules over the fimbriated end of the tube and/or on the ovarian surface through the culdoscope. The recovery of these substances in the vaginal canal is unequivocal evidence of anatomic and function normalcy of the uterine tube.

Critique While the kymographic records obtained through uterotubal insufflation are the only accepted method of measuring tubal peristalsis, these newer procedures warrant trial and exploration. In many circumstances the use of serial hysterosalpingography films with the less viscous agents will demonstrate tubal peristalsis. This area seems one of the most fruitful zones for further investigation and study. It obviously introduces certain problems and technical considerations. However, the simultaneous demonstration of normal tubal patency and functional capacity is of immense value in studying the tubal factor of infertility. Partial or Temporary Closure of the Tube

It is not uncommon for the physiCian counseling an infertile couple to base his advice on the data available, that the wife's tubes appear closed and this is the cause of her infertility. At times the couple have been advised to adopt a child because of the probable permanence of this occlusive phenomenon, and yet we

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have all been confronted with situations in which the patient subsequently became pregnant. Obviously, this tubal occlusion was either partial or transient. A number of publications dealing with this type of tubal occlusion have been recorded in the past few years. Campos da Paz,13 in a study of infertile couples, found 36 of 500 patients in whom the tubal obstruction was only partial. He emphasizes the importance of utilizing insuffiation and hysterosalpingography to demonstrate these partial occlusions. Rubin,n in the description of his refined kymographic recording, states that modification of the tracing will indicate partial tubal obstruction, uterotubal spasm, and other functional states of the tube. Langer and Parks37 considered transient tubal occlusion as a spastic phenomenon similar to vaginismus, frigidity, and other sexual derangements. They attempted to differentiate permanent anatomic occlusion from spasm by use of intravenous antispasmodic agents during hysterosalpingography. Rubenstein38 presents similar evidence of spasmolysis in a group of women by the use of sublingual nitroglycerin. He emphasizes the role of chemical and psychotherapeutic relaxation of such spasms. In a carefully controlled study of 216 women, he indicates that many have tubal spasms which are relieved by psychotherapy and are rewarded by conceptions. Similar experiences are reported by Sandler,39 Seguy,40 and others, all stressing the importance of transient obstruction or spasm which may be relieved by antispasmodic drugs, autonomic blocking agents, or psychotherapy. Sandler implies that 10-15 per cent of tubal occlusion in patients is due to spasm. Marsalek and Zenisek41 take issue with this evidence, believing that such spasm would have to be of long duration to cause infertility. Their study in which they employed the usual antispasmodic drugs has shown an increased muscular tone and amplitude of contractions which, in their interpretation, would have the opposite effect to spasmolysis. Araneda42 studied the relationship of ovarian steroids to uterotubal spasm as determined by kymographic records of gaseous insuffiation. He observed that the spasm and the character of the oscillations could be modified with estrogen and progesterone, and implies that these derangements might be a factor of apparently occluded tubes.

Critique Much has been written in the last few years about spasm of the uterotubal junction, chiefly because everyone has encountered patients in whom the tubes are proved to be closed by the Rubin test or hysterosalpingography or both, and yet these women become pregnant without medical or surgical treatment. Undoubtedly in these women the occlusion detected by tubal insuffiation or hysterography was not an anatomic one, but was due to spasm. The cause, in some women at least, may be a psychic one. We know that

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amenorrhea with suppressed ovulatipn can be due to emotional disturbance, as evidenced in concentration camps during the last war. This effect is brought about by the association between the hypothalamus and the pituitary and the rest of the endocrine glands. Experiments in animals have shown that the hypothalamus controls the adenohypophysis. Ovulation can be induced by stimulating the adenohypophysis. Hence, the activity is transmitted from the hypothalamus to the pituitary. Ovulation can be prevented by removing the pituitary or sectioning its stalk. We know that in some women fear of pregnancy, for example, may suppress a menstrual period. Perhaps, also, psychic trauma may cause tubal spasm.

TUBERCULOUS SALPINGITIS During the past few years there has been an unusual activity and interest in pelvic tuberculosis. A large number of publications dealing with this item has been reviewed and bibliographic references are appended. With the recent great decline in pyogenic infections in the pelvis, considerable interest has centered about tuberculous infection. It is inevitable that the problem of tuberculous pelvic infection would become involved in fertility. During the past several years authors have reported increasing incidences of pelvic tuberculosis in patients with infertility. It has ranged from 1 per cent to almost 15 per cent as reported by Lopez de la Osa. 43 There seems to be slight variation between parts of Europe, South America, and Australia. It is infrequently found in the United States. In those patients with pelvic tuberculosis and infertility the pathology is usually tubal occlusion. Sharman44 tested tubal patency by insufflation and found closed tubes in 67 per cent of the patients. White12 reports that when previous pyogenic infection or abdominal surgery can be excluded, 45 per cent of tubal obstructions are due to tuberculosis. The diagnOSis of pelvic tuberculosis or tuberculous salpingitis can be made by various clinical evidences. Perhaps the best is the clinical history of chronic infection without febrile response, endometrial biopsies and curettage for histologic evidence of tuberculous endometritis, and by presumption, tuberculous salpingitiS. Siegler8 has described the typical radiographic appearance of tuberculous salpingitis.

Prognosis From the standpoint of infertility, it would appear to make little difference whether the tubal obstruction was due to tuberculous inflammatory disease or to other inflammatory processes. Prognosis for recovery of tubal patency after tuberculous infection is about the same as that following other inflammatory obstruction. Sharman,44 Rabau,45 and Kullander46 each reported a case of pregnancy after

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treatment of tuberculous pelvic infection. Jameson-l7 has emphasized that even though tubal patency may be restored by medical therapy, abnormal tubal physiology may persist, leaving the patient incapable of conception. Bellingham48 has reported instances of ectopic pregnancy in tuberculous salpingitis.

Critique Pelvic tuberculosis is more common than is generally believed. In practically all cases the tubes are involved and constitute the primary source of pelvic infection. The uterus is tuberculous in about 70 per cent of the cases, and the ovaries in approximately 30 per cent. The cervix is less often implicated. Since endometrial biopsies have become almost routine in the study of sterile couples, endometrial tuberculosis has been found in many unsuspected cases. In practically every case of endometrial tuberculosis, both tubes are tuberculous. This is most likely the cause of the sterility. A diagnosis of pelvic tuberculosis can generally be based on one or more of the following: (1) history of a chronic illness; (2) palpation of masses in the pelvis; ( 3) slight fever; (4) low white-blood-cell count; (5) no benefit from antibiotics other than streptomycin; (6) improvement with streptomycin, especially when combined with para-aminosalicylic acid (PAS); (7) positive endometrial biopsy; ( 8) positive smears; (9) positive cultures of menstrual blood; and (10) sometimes hysterosalpingography. Only the future will show the proper place of streptomycin, PAS, and the hydrazides of isonicotinic acid in treating genital tuberculosis. In spite of the apparent cures of pelvic tuberculosis as evidenced by disappearance of masses, absence of histologic evidence in endometrial biopsies, failure to find tubercle bacilli in cultures, and even the demonstration of tubal patency by the Rubin test or hysterosalpingography, pregnancy seldom occurs and a live child is a rarity. Let us hope that in the near future new drugs will be found to restore the procreative function of women afflicted with pelvic tuberculosis.

THERAPY The role of several therapeutic procedures for the tubal factor in infertility has been amply discussed in the literature during the past several years. It involves tubal insufflation, iodized contrast media, psychotherapy, spasmolytic drugs, hormones, and surgery. Undoubtedly, each of these has its own specific part to play. Weir and Weir 4v made an interesting study of sex education and the proper timing of exposure in a series of 32 infertile couples. Five of the 32, approximately 15 per cent, conceived through sex education alone. Fifteen, or approximately 50 per cent, conceived after hysterosalpingography (at least within 7 ovulations thereafter). Twelve women, approximately 25 per cent, remained infertile. The authors concluded that the probability of conception during the first 2 ovula-

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tions following salpingography is enhanced. However, one cannot ignore the rather large number of women who either conceived without such technic or remained infertile despite it. Sharman's44 extensive study reports that 17 per cent of the patients became pregnant when treated by uterine sound alone. Snaith,50 studying the tubal factor in 1524 sterility cases, found that 13 per cent conceived without receiving any specific therapy. These and other observations cast considerable doubt on the importance of any specific therapeutic agent for infertility. Psychotherapy

Langer and Parks 37 studied the emotional reaction to sexuality and believe that a conscious and subconscious fear of pregnancy results in spasmodic tubal occlusion. Rubenstein 38 makes similar observations and recommends psychotherapy and the development of excellent patient-physician rapport. It is obvious that psychotherapy will cure tubal infertility of tubal origin only when spasm is present. Sandler39 has observed that in many cases spasm is not relieved by reassurance. Medical Therapy

Medical therapy in tubal disease is broad in its scope. The use of antibiotic agents, alone or in conjunction with other treatment of pelvic infection, is well established. Employment of para-aminosalicylic acid and isonicotinic acid for pelvic tuberculosis is now common practice. The few pregnancies reported after medical therapy of pelvic tuberculous salpingitis have followed such therapy. Ryden and Westgren31 combine the use of antibiotics with radiopaque substances in hysterosalpingography for its therapeutic benefit on endosalpingitis. The high incidence of ectopic gestation following pelvic inflammatory disease indicates that many of the inflammations may heal and produce temporary or partial tubal occlusion. Certainly concomitant with utilization of antibiotic therapy there has been an increase in ectopic gestation. Whether these two observations are related has yet to be confirmed. Many patients have been treated by spasmolytic drugs. Marsalek and Zenisek41 believe that this therapy is useless since, in their opinion, such spasm would be too short to significantly affect fertility. Rubenstein38 has used nitroglycerin for both diagnosis and therapy. The therapeutic value of spasmolytic agents is still uncertain and the beneficial results reported have yet to be substantiated.

Insufflation The importance of hysterosalpingography and uterotubal insufHation in the treatment of infertility is well established. Sharman,44 Zanartu and Hamblen,IH and Vesell52 report pregnancies following hysterosalpingography or insufHation.

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Similar observations were noted by Rubin;ll Mackey/6 Weir and Weir;49 Calzolari;53 Keryell;14 Vogt;17 Woltz, Bradford, Bradford, and Brown;54 Roland, Carpenter, and Rich;23 and others. It is obvious that the various methods of testing tubal patency also have therapeutic value. Each of the authors reports large series of cases and claims some superiority for his particular agent or method. Calzolari53 maintains that repeated hysterosalpingography can cure infertility caused by tubal occlusion, and he never admits permanent sterility until this opportunity has been exhausted. Woltz, Bradford, Bradford, and Brown54 have a similar opinion. Vesell52 reports that, in his hands, insufHations have yielded more successes and fewer complications than plastic operations on the tubes. Snaith,50 on the other hand, casts doubt on the therapeutic value of either of the two patency tests. In 776 cases of pregnancy after one or more insufHations or hysterosalpingography, he concluded that pregnancy could be attributed to their therapeutic effect in 31 per cent, pOSSibly attributed in 19 per cent, and definitely not attributable in 50 per cent. The evidence of the superiority of gas or oil- or water-soluble agents is difficult to support from the variety of statistical data available in this survey of the literature. Araneda42 studied the effect of sex steroids on uterotubal function and believes that they are helpful in modulating uterotubal peristalsis. Snaith50 had a small series of patients in whom similar beneficial results apparently followed the use of estrogen. Whether these results were in altered tubal peristalSiS, enhanced ovulatory stimuli, improvement in cervical mucus, or other factors is not well delineated. Kurzrok and Streim 55 used Cortogen therapy to soften and dissolve adhesions blocking the fallopian tubes. Conception occurred in 5 of their 8 patients, the pregnancy being an intrauterine gestation in each case. In the other 3 patients definite patency of the tubes was obtained; however, only one was permanent. The authors felt that they should have continued therapy beyond the time that patency was reestablished instead of stopping as soon as the tubes had opened. No harmful effects were produced. Surgical Procedures

Surgery remains the most enticing form of therapy for tubal occlusion in infertility. While emphasis has been placed on tubal patency, there is increasing importance attached to tubal function. Kviz 56 emphasizes this functional feature and believes surgery for the infundibular portion of the tube should be condemned. By proper selection of cases he reported 22 per cent success in tubal surgery. Weinstein57 advances similar views on the importance of physiologic restoration of the tube. The percentage of successful pregnancies following tubal surgery is distressingly low, ranging from near zero to 35 per cent.58-62 Hartnett and Hartnett63

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report tubal patency in 66 per cent of their patients, but pregnancy in only 28 per cent; viable children were even less frequent. Similar views are expressed by Langley.64 Buxton and Southam introduce a skeptical note by indicating an almost equal incidence of pregnancy in patients operated on for tubal obstruction as for those refusing surgery.

Reconstruction An interesting and hopeful note has appeared with regard to conservative or reconstructive surgery in patients with ectopic pregnancy. Grant,65 Szendi,66 and Jarvinin, 67 present evidence that this procedure has value. While the incidence of repeat ectopic gestation is high, the resulting frequency of living children far exceeds that in other forms of tubal surgery.

Reimplantation There are several surgical technics available for consideration. The employment of reimplantation is reported by Green-Armytage,68 d'Igianni and Fontenelle,69 Alvarez Bravo,7o and others, with satisfactory results varying from 18 to 35 per cent.

Polyethylene Tubing The utilization of polyethylene tubing has been extensively studied. It has been used in some of the reimplantation problems as reported by GreenArmytage,68 Mulligan, Rock, and Easterday,71 and others. Tubal patency is frequent, but viable gestations are disappointingly infrequent. In this regard, experience with refertilization after deliberate tubal sterilization as reported by Traenckner72 and Paukstis,73 presented poor results in fruitful pregnancies. In an effort to find other methods for enhanCing tubal function, several ingenious procedures have been explored. Mulligan, Rock, and Easterday71 constructed a hood of polyethylene plastic over the reconstructed tubal end and believe it to offer opportunities for clinical use.

Transplantation A similar technic is reported by Ten Berge and Tik Lok,H who used amniotic membrane for the formation of a bursa. While the operation was anatomically successful, no pregnancies have resulted to date. Davids and Bellwin75 reported successful construction of the tube in dogs by the use of vein and artery transplants. They believe this to be a practical procedure.

Estes Operation And lastly, the Estes operation or ovarian-uterine transplantation has been

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restudied and reported by Mocquot and Thoyer-Rozat7 6 and Preston. 77 The latter reported 14 per cent successful pregnancies.

Critique Almost 20 years ago I wrote a pessimistic paper77A about surgical operations performed on the fallopian tubes to overcome obstruction. The basis for my pessimism was the fact that after 818 plastic operations performed by gynecologic specialists in the United States, there were only 54 pregnancies, or 1 gestation for every 15 operations, an incidence of 6.6 per cent. However, since only 36 live babies were born, the incidence of success after operation was only 1 in 22.5 operations, or 4.4 per cent, a very poor showing indeed. Ten of the 54 pregnancies (18.5 per cent) ended in abortion, and 8 (14.8 per cent) were tubal pregnancies. Hence, only two thirds of the 54 pregnancies resulted in live children, and one seventh of the women had to have a second laparotomy for a tubal pregnancy. In recent years my pessimism has been supported by a few gynecologists and contradicted by some who obtained far better results than were observed many years ago. In an effort to see whether today's results are far better than those I reported 20 years ago, Siegler and Hellman sent questionnaires to 4910 specialists in the United States and abroad and received 734 replies. Briefly, their results were as follows: There were 513 pregnancies, an incidence of 22.6 per cent, for the entire series as contrasted with 6.6 per cent for mine. The incidence of tubal pregnancies was 9.1 per cent, and in my series it was 14.8 per cent. In the former group, abortions occurred in 15.4 per cent and in my series in 18.5 per cent. * I have written to practically every gynecologist in the world who has been studying the problem of surgical operations on the fallopian tubes, to obtain their present results. With few exceptions, even in the hands of these experts who are constantly experimenting with tubal plastic operations, the results are not too good. My analysis will be reported later. I raise the question: Are we justified in recommending abdominal surgery when we cannot promise these women more than 1 chance in 4 or 5 of having a baby? Also, we must be honest enough to tell the patient that the chance of having a tubal pregnancy which requires a second operation is increased greatly following this type of surgery. The relatively low incidence of success today (in my opinion) is that obtained by surgeons who are skilled in this type of surgery; hence, it is reasonable to deduce that tubal plastic operations performed by gynecologists and general surgeons who seldom resort to such operations will yield fewer successes and perhaps more ectopic pregnancies. As I said almost 20 years ago, the following conditions should be present before a plastic operation on the tubes is performed: The patient must be in the childbearing period, preferably under 35 years of age; she must have at least one functioning ovary; both tubes or the only tube present must have been proved closed; there must * Results of the questionnaire appears in paper by Siegler and Hellman, this issue, p. 170.

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be no other cause for sterility than tubal closure; there must be no tuberculous infection in the genital tract; and the patient must be a good surgical risk. Of course, the husband must be fertile and healthy. I, personally, am pleased that many gynecologists in different parts of the world are attempting to improve the results of tubal plastic surgery because the article I wrote in 1936 was most pessimistic. In spite of the fact that considerable time, effort, and ingenuity have been put into the improved technics, the incidence of live babies is still too low. These experimental studies should be continued and extended. Undoubtedly, technics will be developed enabling about 50 per cent of women to conceive in the uterus after the operation, thus making such operations definitely worthwhile. In the meantime, I make a plea that all women who are candidates for plastic operations on the tubes be referred to gynecologists who are studying the problem, and who have perfected special technics, using tiny instruments, fine suture material, polyethylene tubing, and other aids to improve the results of tubal operations.

SUMMARY AND CLINICAL APPLICAnON The tubal factor continues to be of extreme importance in infertility and is the greatest single cause of infertility in women. It has been clearly established by both clinical and laboratory studies that the tube is a functional structure, not a conduit. It plays an important role in receiving the ovum and the spermatozoa, and in facilitating fertilization and migration of the embryo into the uterus. Tubal patency is now recognized as incomplete evidence of normal tubal function. Many diagnostic tests are available for tubal patency, and it would appear that uterotubal insuffiation, radiography, and retrograde instillations are all effective, each having its own advantages and limitations. The tests are complementary rather than competitive. In the final survey, radiographic evidence is usually necessary to certify tubal closure and to indicate its location and type. When radiographic technics are employed, the advantages of safety and low toxicity present strong recommendations for the aqueous or polyvinyl agents. It is probable that increasing emphasis will be placed on tubal-function tests. The kymographic records of the Rubin test are valuable in this regard, but other tests may be explored and developed to demonstrate normal tubal physiology and probable normal fertility function. The pitfalls of diagnosing tubal disease in infertility are again stressed and one cannot emphasize too much the need for meticulous attention to detail. This is particularly true in spasm and other temporary or partial obstructions. The treatment of tubal disease in infertility is disappointing, whether it be psychotherapy or medical or surgical therapy. The results of each seem about equal. In fact, one is impressed with the value of "self"-therapy, as indicated by the number of women who are either gravid at the time of the initial visit or

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become so during diagnosis and prior to therapy. These observations provide a sobering effect to our unwarranted enthusiasm for special technics or procedures. This holds true not only for tubal factors, but for the whole area of infertility study and treatment. Careful study of the infertile couple, including the tubal factor, will result in better selection of patients for treatment, and better results in the form of more successful pregnancies.

J.

P. GREENHILL, M.D. Chicago, Ill.

REFERENCES l. JEFFCOATE, T. N. A. Tubal patency tests. Proc. Soc. Study Fertil. 5:1, 1953. 1A. HARTMAN, C. G. Time of Ovulation in Women. Baltimore, Md., Williams & Wilkins, 1936. 2. WESTMAN, A. In ENGLE, E. T.: Studies on Testis and Ovary: Eggs and Sperm. Springfield, Ill., Thomas, 1952. 2A. BLANDAU, R. J. Ovulation in the living albino rat. Fertil. & Steril. 6: 391, 1955. 3. STANGE, H. H. Comparative morphological study of the human oviduct in extreme functional states to elucidate the question of whether a sphincter infundibuli exists. Zentralbl. Gyniik. 74:1176, 1952. 4. DOYLE, J. B. Exploratory culdotomy for observation of tubo-ovarian physiology at ovulation time. Fertil. & Steril. 2:475, 1951. 5. HERRLINGKOFFER, K. M. The muscle layer of the human oviduct. Ztschr. Geburtsh. u. Gyniik. 188:63, 1953. 6. LISA, J. R., GIOIA, J. R., and RUBIN, I. C. Observations on the interstitial portion of the fallopian tubes. Surg. Gynec. & Obst. 99:159,1954. 6A. BLANCHARD, O. Personal communication. 7. DE PAEPE, J. Lesions of the isthmus tubae. Gynt?c. et obst. 4:286, 1952. 8. SIEGLER, A. M. Diverticulosis of the fallopian tubes. Fertil. & Steril. 6: 432, 1955. ------ Tuberculosis of the uterine

9.

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tubes: A roentgenologic study of eight cases. Obst. & Gynec. 6:180, 1955. CHANG, M. C. Fertilizing capacity of spermatozoa deposited into the fallopian tubes. Nature, London 168:697, 1951. TONI, G., and MACCAFERRI, A. Thickness and number of the smooth muscle cells of the fallopian tube at various ages. BoU. Soc. ital. biol. spero 27:1117, 1951. RUBIN, I. C. Forty years' progress in the treatment of female sterility. Am. J. Obst. & Gynec. 68:324, 1954. - - - - - Comparison of carbon dioxide and opaque media in the diagnosis of tubal patency. Fertil. & Steril. 3: 179, 1952. WHITE, M. M. Errors in technique and interpretation of hysterosalpingography. ]. Obst. & Gynaec. Brit. Emp. 58:573, 1951. CAMPOS DA PAZ, A. Partial tubal obstruction. Rev. brasil. cir. 24:407, 1952. KERYELL, J. Comparison of results obtained by kymographic uterotubal insufHation and hysterosalpingography in the investigation of sterility in women. Compt. rend. Soc. fran y. gynec. 23:217, 1953. ZENISEK, L. A comparison of the diagnostic results of kymographic insufHation and hysterosalpingography. Ceskoslov. gynaek. 17:96, 1952. MACKEY, R. Endometriosis and sterility. M.]. Australia, p. 168, 1954.

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17. VOGT, C. J. Hysterosalpingography: A safe diagnostic and therapeutic Am. J. gynecological procedure. Obst. & Gynec. 67: 1298, 1954. 17A.GREENHILL, J. P. Year Book of Obstetrics & Gynecology. Chicago. Yr. Bk. Pub. 1953-54, pp. 308-9. 18. BENDICK, A. J. A simplified, inexpensive technique in hysterosalpingography. Surg. Gynec. & Obst. 99: 642, 1954. 19. FREETH, D. Hysterosalpingography in female infertility: A comparison of Lipiodol and Viskiosol Six. Lancet 1: 1.5, 1952. 20. JACKSON, M. H. Ethiodan (or Pantopaque) as a contrast medium for Froc. Soc. hysterosalpingography. Study Fertility 5:10, 1953. Hysterosalpingog21. HUBSCHER, K. raphy with Joduron-S. Med. arkh. 7:69,1953. 22. RUBIN, 1. C., MYLLER, E., and HARTMAN, C. C. Salpix: New approach to ideal radiopaque medium for hysterosalpingography. Fertil. & Steril. 4:357, 1953. 23. ROLAND, M., CARPENTER, F., and RICH, J. A new water-soluble opaque medium for the study of hysterograms and hysterosalpingograms. Am. /. Obst. & Gynec. 65:81, 1953. 24. PALMER, R., and PULSFORD, J. Hysterosalpingography with water-soluble viscous contrast media and manometrical registration: Diagnosis of tubal stenosis. Bull. Fed. soc. gyruic. et obst. 4:676, 1952. 25. MULLER, C. Dber die Bedeutung des Druckes bei der Hysterosalpingographie (HSC) und liber ein neues Instrument zur Druckmessung. Schweiz. med. Wchnschr. 81 :639, 1951. 26. ZACHARIAS, F. Venous and lymphatic intravasation in hysterosalpingography. Acta obst. et gynec. scandinav. 34:131, 1955. 27. BERGMAN, F., NORMAN, 0., and SJOSTEDT, S. Foreign body granuloma after hysterosalpingography with

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Umbradil-Viskos II. Svenska liik.siillsk. forhandZ. 49: 1774, 1952. AARON, J. B., and LEVINE, W. Endometrial oil granuloma following hysterosalpingography. Am. /. Obst. & Gynec. 68:1594, 1954. PALMER, A. Lipiodol 'F' for use in hysterosalpingography. FertiZ. & SteriZ. 3:210, 1952. BROWN, W. E., and JENNINGS, A. Evaluation of various media used in hysterosalpingography. Tr. Soc. Study SteriZ. pp. 50-6, 1947. RYDEN, A. B. V., and WESTGREN, A. Inflammatory complications of hysterosalpingography and their prevention. Acta obst. et gynec. scandinav. 33:109, 1954. DAVIS, M. E., WARD, M. E., and KING, A. C. An evaluation of the PSP (Speck) test for tubal patency. Fertil. & SteriZ. 3:217, 1952. HERSTEIN, A. Culdoscopy: An adjunct in gynecological diagnosis. Am. /. Obst. & Gynec. 69:240, 1955. SHEFFERY, J. B. A new method of determining tubal patency and tubal ciliary activity. South. M. J. 47:221, 1954. STABILE, A. Interpretation of manometric oscillations observed during uterotubal insufflation. Fertil. & Steril. 5: 138, 1954. --.---- Our interpretation of rhythmic alterations in the kymograms in uterotubal insufflation: Necessity for a rectification of the concept. Obst. y ginec. latino-am. 10:40, 1952. DECKER, A., and DECKER, W. H. A tubal function test. Obst. & Gynec. 4:35, 1954. LANGER, M., and PARKS, O. R. Psychogenic spasm of the oviducts as a factor in sterility: Its pathogenesis and treatment. Rev. med. ginec. Af. 15: 164, 1953. RUBENSTEIN, B. B. A tubal factor in functional sterility in women. Rev. espan. obst. y ginec. 13: 1, 1954. SANDLER, B. The mechanism of

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tubal spasm. Proc. Soc. Study Fertil. 5:50,1953. SEGUY, J. Bilateral tubal obliterations at the uterine end shown by hysterography. Semaine hOp. Paris 28:3549, 1952. MARSALEK, J., and ZENisEK, L. Can tubal spasm be influenced by spasmolytic drugs? Uk. listy 7 :419, 1952. ARANEDA. Effects of ovarian steroids on uterotubal insuffiation. Bal. Soc. chilena obst. y ginec. 18:270, 1954. DE LA OSA LOPEZ. Tuberculous endometritis in sterility. Acta ginec. madrid 4:417, 1953. SHARMAN, A. Some lessons from 4,000 uterotubal insuffiations. Brit. M. ]. 1 :239, 1954. RABAU, E. Genital tuberculosis in the female. J. Obst. & Gynaec. Brit. Emp. 59:743, 1952. KULLANDER, S. Endometrial tuberculosis treated with para-amino-salicylic acid (PAS): Report of case with subsequent pregnancy. Glasgow M. ]. 33:395, 1952. JAMESON, E. M. Modern treatment of tuberculosis and the gynecologist. Am. ]. Obst. & Gynec. 66: 1131, 1953. BELLINGHAM, F. A. Tubal tuberculosis and pregnancy. M.]. Australia 1 :700, 1954. WEIR, W. C., and WEIR, D. R. Therapeutic value of salpingograms in infertility. Fertil. & SteTil. ~:514, 1951. SNAITH, L. The tubal factor in female subfertility. Practitioner 169: 140, 1952. . ZANARTU, J., and HAMBLEN, E. C. Investigations on the diagnosis and treatment of tubal obstruction by hysterosalpingography: 400 Cases. Ann. Ostet. & Ginec. 75:855, 1953. VESELL, M. Multiple uterotubal insuffiations in cases of sterility due to tubal occlusion. Am. ]. Obst. & Gynec. 68:8lO, 1954. CALZOLARI, G. Diagnostic importance and therapeutic possibilities of repeated hysterosalpingography in

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sterility due to tubal occlusion. Arcisped. S. Anna (Ferrara) 5:341, 1952. WOLTZ, J. H. E., BRADFORD, W. Z., BRADFORD, W. B., and BROWN, C. W. The treatment of infertility in private practice with emphasis on hysterosalpingography. Am. J. Obst. & Gynec. (j6:801, 1953. KURZROK, L., and STREIM, E. Cortogen treatment for sterility due to nonpatent tubes. Fertil. & Steril. 5: 515, 1954. KVIZ, D. Surgical treatment of tubal sterility. Csl. gynaek. 17 :88, 1952. WEINSTEIN, B. B. Indications for surgical intervention in sterility of the female. South. M. J. 44:1135, 1951. PALMER, R. Results of surgical treatment of tubal obstruction. Gymk. et obst. 4:497, 1952. ------ Results of surgical treatment of tubal occlusion. Bruxellesmed. 33:1449, 1953. LA FORGE, H. G. Clinical value of uterosalpingography. N. Y. State ]. Med. 51 :21, 1951. CARTER, B., TURNER, V. H., DAVIS, C. D., and HAMBLEN, E. C. Evaluation of gynecologic surgery in therapy of infertility. ].A.M.A. 148:995, 1952. GALLOWAY, C. E. Surgical aspects of sterility. Fifth Am. Congo Obst. & Gynec. 64A:40, 1952. AMARAL FERREIRO, C. Restorative surgery in treatment of sterility. Anais brasil ginec. 19:229, 1954. HARTNETT, L. J., and HARTNETT, D. C. Interstitial occlusion of fallopian tube: Consideration of its surgical treatment. Am. ]. Obst. & Gynec. 64:637, 1952. LANGLEY, 1. 1. The use of polyethylene in tuboplasty. West.]. Surg. 63:395, 1955. GRANT, A. Problems in fertility and sterility due to ectopic pregnancy: A study of 259 cases. M.]. Australia 2:817, 1953. SZENDI, B. Usefulness of conserva-

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tive surgery in tubal pregnancy. Gynecologia 136:327, 1953. JARVININ, P. A. Later fertility after conservative operation for tubal pregnancy. Ann. chir. et gynaec. Fenniae 43: 185, 1954. CREEN-ARMYTAGE, V. B. Tubo-uterine implantation. Brit. M. ]. 1: 1222, 1952. ------ La chirurgie de la sterilite par obturation Tubaire. Gynec. Pratique 5:3, 1954. D'INGIANNI, V., and FONTENELLE, 1. L. Implantation of the salpinx employing a cannula. South. M. I. 44:12, 1951. ALVAREZ BRAVO, A. Role of surgery in treatment of sterility in women. Estud. Esterilidad 3: 119, 1952. MULLIGAN, W. J., ROCK, J., and EASTERDAY, C. L. Use of polyethylene in tuboplasty. Fertil. & Steril. 4:428, 1953. TRAENCKNER, K. Refertilization after sterilization on "eugenic" grounds: Results of refertilization operations in

Fertility & Sterility

Hamburg. Arch. Gyniik. 182:387, 1953. 73. PAUKSTIS, C. A. Restoration of conceptive ability following surgical sterilization. J. Mich. S. M. Soc. 50: 1238, 1951. 74. TEN BERGE, B. S., and TIK LOK, T. Plastic surgery of closed tubes with chorion-amnion. Fertil. & Steril. 5: 339, 1954. 75. DAVIDS, A. M., and BELLWIN, A. Reconstruction of fallopian tubes by vein and artery transplants. Fertil. & Steril. 5:325, 1954. 76. MocQuoT, M., and THOYER-RoZAT, J. Bull. Fed. soc. gynec. et obst. de langue fran y. 6:402, 1954. 77. PRESTON, P. C. Transplantation of the ovary into the uterine cavity,for the treatment of sterility in women. J. Obst. & Gynaec. Brit. Emp. 9:6, 1953. 77A. GREENHILL, J. P. Evaluation of salpingostomy and tubal implantation for the treatment of sterility. Am. J. Obst. & Gynec. 33:39, 1937.

FURTHER REFERENCES ASPLUND, J., and RYDEN, A. B. V. Diagnosis of tuberculosis of cervix. Acta obst. et gynec. scandinav. 31: 186, 1952. BECKER, M. S., MARBACH, H., and SCHINFELD, L. H. Intestinal obstruction following use of a water-soluble contrast medium (Medopaque-H) in hysterosalpingography. Am. I. Obst. & Gynec. 69:917, 1955. BEDRINE, H., and HOULNE, P. Endometrial tuberculosis: Cultures of biopsy specimens in diagnosis, treatment and follow-up. Cynec. et obst. 4:280, 1952. BOBROW, M. L., BLINICK, C., and SOICHET, S. Pelvic tuberculosis and pregnancy. Am. I. Obst. & Gynec. 66:1280, 1953. BOBROW, M. L., and BATTS, J. A. Pelvic tuberculosis. Am. I. Obst. & Gynec. 64:1242, 1952. BONNET, L. Hydrosalpinx studied by kvmographically measured insufHation. Gynec. et obst. 52:56, 1953.

BOTELLALLUSIA, J., NOGALES, F., BEDOYA, J. M., and VELAR, E. Uterine tuberculosis. Rev. Obst. y Ginec. Caracas 11: 26, 1951. BROWN, A. B., GILBERT, C. R. A., and TE LINDE, R. W. Pelvic tuberculosis. Obst. & Gynec. 2:476, 1953. BURNE, J. C. Schaumann bodies in tuberculous salpingitis. I. Path. & Bact. 65: 101, 1953. CASTALLO, M. A., and WAINER, A. S. Polyethylene intubated salpingoplasty: A newer approach to closed tube sterility. Am. I. Obst. & Cynec. 66:385, 1953. DONALDSON, I. A. Pelvic tuberculosis and pregnancy. Brit. M. I. 2: 128, 1952. EKENGREN, K., and RYDEN, A. B. V. Roentgen diagnosis of tuberculous endometritis. Acta radial. 36:485, 1951. ELGUETA, H., and PENA, C. La hidrazida del acido isonicotinico isoniazoda en el

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tratamiento de la tuberculosis pelvica. MAGNUSSON, W. On the localization of Bol. Soc. chilena ohst. y ginec. 18:125, tubal obstruction in cases of sterility 1953. from different causes. Acta radiol. 41: FIKENTSCHER, R. Surgical treatment of 513, 1954. female sterility. Gehurtsh. u. Frauenh. MILLAR, W. G. Investigation and treat13:1053, 1953. ment of female genital tuberculosis. J. GRAY, L. A. Hysterosalpingography. Ghst. & Gynaec. Brit. Emp. 61 :372, Radiology 61: 189, 1953. 1954. HAINES, M. Genital tuberculosis in the MORRISON, J. K., and EALAND, C. T. F. female. ]. Ghst. & Gynaec. Brit. Emp. Post-partum genital tuberculosis. J. 59:721, 1952. Ghst. & Gynaec. Brit. Emp. 61 :661, HALBRECHT, 1. Latent female genital 1954. tuberculosis: Further studies in its diag- NOGALES, F. Tuberculosis of cervix: Evalnosis, prognosis and treatment; report uation of histopathology; clinical picture on 100 cases. Gynaecologia 136:321, and treatment in 46 cases. Arch. Gyniik. 1953. 184:139, 1953. HORN, P. Gynecologic tuberculosis. Ann. O'DRISCOLL, D. T. Genital tuberculosis West. Med. & Surg. 5:926, 1951. with pulmonary involvement: ObservaKIKA, K. Clinical analysis of "angiotions, incidence and treatment. Lancet grams" found in course of hysterosal2:476, 1951. pingography with special reference to PALMER, R., and PROUST, G. Data on 40 tuberculosis of female genitals. Am. J. cases of ampullo-uterine implantation. Ghst. & Gynec. 67:56, 1954. Bull. Fed. soc. gynec. et ohat. 5:548, KNAUS, H. Pathological anatomy and 1953. clinical aspects of genital and peri- ROZIN, S. The x-ray diagnosis of genital toneal tuberculosis in females. Med. tuberculosis. J. Ghat. & Gynaec. Brit. Klin. 49:593, 1954. Emp. 59:59, 1952. ------ Diagnosis and therapy of female ROZIN, S., and BROMBERG, Y. M. Effect genital tuberculosis. Med. Klin. 48: of antituberculosis treatment in sterility 549, 1953. due to genital tuberculosis. Acta med. ------ Zur operativen Behandlung der orient. 12: 197, 1953. weiblichen genital tuberkulose. Wien. RYDEN, A. B. V. Value of antibiotics in Klin. Wchnschr. 65:404, 1953. the treatment of female genital tubercuLATTIMER, J. K., COLMORE, H. P., SANlosis. Acta ohst. et gynec. 8candinav. GER, G., ROBERTSON, D. H., and Mc32:380, 1953. LELLAN, F. C. Transmission of genital SANDLER, B. Tubal palpator for salpingtuberculosis from husband to wife via ography. Lancet 2:524, 1950. the semen. Ann. Rev. Tuherc. 69:618, SEGOVIA, S., and BUNSTER, E. Strepto1954. mycin and para-aminosalicylic acid in LEROUX, M., and GUIHENEUC, B. o. Pretreatment of genital tuberculosis. Bol. miere resultats de la streptomycinoSoc. chilena. ohst. y ginec. 16:276, 1951. therapie dans la tuberculose genitale feminine. Gynec. et ohst. 49:479, 1950. SERED, H., FALLS, F. H., and ZUMMO, B. P. Treatment of female genital tuberculosis LEVINE, W., and KURLAND, 1. I. Detecwith streptomycin and para-aminosalition and treatment of unsuspected tucylic acid. Am.]. Ghst. & Gynec. 66: berculous endometritis. Am. J. Ghst. 823,1953. & Gynec. 63:420, 1952. LIL}EDAID.., S. 0., and RYDEN, A. B. V. - - - - - Streptomycin in genital tuberculosis of the female: Further observations. Diagnosis and treatment of genital tuber].A.M.A. 148:521, 1952. culosis in women. Acta ohst. et gynec. STALLWORTHY, J. Genital tuberculosis in scandinav. 30:359, 1951.

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the female. J. Ghst. & Gynaee. Brit. Emp. 59:729, 1952. SUZUKI, M. Streptomycin therapy for asymptomatic endometrial tuberculosis. Ghst. & Gynee. 5:142,1955. SUTHERLAND, A. M., and GARREY, M. M. Female genital tuberculosis: 20-Year survey. Glasgow M. ]. 82:231, 1951. SWAAB, L. I. Tuberculosis of genital orNederl. tijdschr. gans in female. geneesk. 95:442, 1951. TEN BERGE, B. S. Chorion-amnion-salpingolysis for closed fallopian tubes. Nederl. tijdsehr. geneesk. 97:133, 1953. THoM, H. Dber die Genitaltuberkulose der Frau: Nach Obduktionsbefunden

Fertility & Sterility

der letzten 30 Jehre. Gehurts. u. Gyniik.12:651, 1952. VERHAGEN, A. Chronic inflammatory changes following Lipiodol hysterosalFortschr. Geh. Roentpingography. genstrahlen 77 :96, 1952. VOKAER, R., ROUTE, J., and GHISLAIN, A. The diagnosis of genital tuberculosis by exfoliative cytology. Bruxelles med. 88: 1311, 1953. WEINER, W. M. Salpingostomy for sterility. J. Internat. Coll. Surg. 28:432, 1955. ZEITZ, H. The question of hysterosalpingography in female sterility with evaluation of clinical results. Gehurts. u. Frauenh. 14:533, 1954.