An odyssey through the oviduct

Transcription

1 FERTILITY AND STERILITY Copyright 'c 1983 The American Fertility Society VoL 39, No, 2, February 1983 Prinred in U.SA An odyssey through the oviduct Victor Gamel, M.D. University of British Columbia, Vancouver, British Columbia, Canada i' r I I' I' i, I: Ii Ii i 1: II II I, "Come then, take tools of bronze, cut long beams and fashion them into a wide raft. Then build half-decks on it well above, so that the craft may carry you over the misty ocean.,,1 So said the goddess Calypso to brave Ulysses after granting him his freedom, and so commences his eventful journey. The most ancient and mysterious, the most complex and exciting mammalian odyssey, the one that brings forth the most precious gift of all, is the odyssey of the gametes. This is a heroic journey through realms totally unknown, and like that of Ulysses, greatly influenced by celestial or external forces; ajourney of great risk, that of death, and of great reward, that of immortality. Does not the oviduct represent this journey's great and misty ocean? We find a fairly good insight about the oviduct in Ayur-Veda, which dates ten centuries before Christ: "The menses have two canals, the roots of which are the uterus... When they are wounded, barrenness is caused..."2 Rufus from Ephesus, not too far away from where I spent my childhood, said, "Females have not a vas deferens, but we have seen in the uterus of a sheep varicose vessels on either side springing from the female testicles; these opened into the cavity of the uterus.,,3 The oviduct, or fallopian tube, is named after Gabriele Fallopio, who, after accurately describ- Received September 1, Presented at the Thirty-Eighth Annual Meeting of The American Fertility Society, March 20 to 24,1982, Las Vegas, Nevada, Winthrop Lecture. Reprint requests: Victor Gomel, M.D., Professor and Chairman, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V Gomel An odyssey through the oviduct ing the isthmic and ampullary segments of the oviduct, wrote: "... and becoming very broad has a distinct extremity which appears fibrous and fleshy through its red color and its end is torn and ragged like the fringe of well-worn garments; and it has a wide orifice resembling that of a brass trumpet, wherefore since the seminal duct from its beginning to its end has a likeness to this classic instrument, it has been called by me the uteri tubae.,,4 GAMETE TRANSPORT The fallopian tube is a complex but delicate organ that performs numerous functions. It is a remarkable organ which is influenced by the ovarian hormones and the numerous parts of which function harmoniously, like those of an orchestra, to achieve the desired goal. At the time of ovulation, human fimbriae are fringed, fluted, and lanciform, the most complex of any mammalian species. More than one-half of the mucosal cells are ciliated cells, which form an intricate pattern. 5 The cilia all beat in the direction of the tubal ostium. At the time of ovulation, muscular contractions displace the fimbriae of the oviduct, and they almost completely surround the ovary. The ciliary movements sweep the ovulated egg in cumulus from the surface of the ovary into the ampulla. The ampullary mucosal folds at the time of ovulation are of an extreme complexity, and the lumen of the ampulla is completely filled with interdigitating folds. This can be best observed in a frozen section of the human ampulla. Only a potential space is left; indeed, the folds separate as the egg in cumulus is moved through the ampulla.

2 More than 50% of the ampullary inucos!ll cells are ciliary, and all of the cilia beat toward the ampullary-isthmic junction (AIJ). The primary transport mechanism of the egg in cumulus through the ampulla is this ciliary mechanism. Blandau and co-workers6 have demonstrated that in the woman it requires approximately 30 minutes for the ovum to be transported through the ampulla to reach the AIJ. Indeed, when smooth muscle activity is blocked pharmacologically in vivo by the intravenous administration of isoproterenol, the rate of transport does not change. Hundreds of millions of spermatozoa are deposited in the vagina. Only a few of these reach the proximal ampulla, the site of fertilization. The manner by which sperm reach this site is still surrounded by considerable mystery. During the preovulatory period, the cervical canal and cervical mucus acquire distinct changes that make them most hospitable to sperm. The canal is somewhat dilated; the mucus is abundant, crystal clear, very stretchable, and contains very few cells-members of the orchestra playing in tune! In women, do spermatozoa move through the cervical mucus by their own innate motility? On the basis of the available evidence, they are certainly able to do so. Surprisingly, however, they are found in the oviduct much faster than their own speed would allow. Of the millions of spermatozoa deposited in the vagina, only a minute percentage reach the uterine cavity. How those entering the uterine cavity reach the uterotubal junction (UTJ) and enter the oviducts is still a mystery.7 Uterine contractions, perhaps enhanced by prostaglandins present in the seminal plasma, may hasten the transport of the uterine contents toward the oviduct. Do the UTJ and the interstitial oviduct act as a selective trap through which only a few sperm enter the isthmus? We do not know. These are problems for the younger generation to resolve. The isthmus has a much thicker muscularis than the ampulla, against a narrower lumen, with much less intricate folds and fewer ciliary cells. The contractile activity of the isthmus is remarkable in that it varies with the phase of the reproductive cycle. Its function is strictly under hormonal control. Observations on the contractile activity of the monkey isthmus in vivo during the preovulatory period and that of the human isthmus in vitro demonstrate antiperistaltic contractile waves that propel the contents of the lumen in a pro-ovarian direction into the ampulla. Dur- ing each antiperistaltic contraction wave, the lumen is completely occluded. This complete occlusion carries its contents forward as a continuous column. In summary, the transport of the luminal contents of the isthmus during the preovulatory and ovulatory periods is essentially pro-ovarian and represents the primary mechanism for the transport of spermatozoa into the ampulla. During the early luteal phase, the contractile activity of the isthmus changes dramatically to a random collection of pro-ovarian and pro-uterine waves of widely varying speeds, which shuttle the ovum backward and forward from loop to 100p.6 The ovum eventually reaches the UTJ and is expelled into the uterine cavity. STUDIES OF THE MORPHOLOGICALLY ALTERED OVIDUCT Up to 10 years ago, a great deal of functional importance was attributed to anatomic landmarks such as the AIJ and the UTJ. The precision afforded by microsurgical techniques and the lack of deleterious effects associated with these interventions have permitted the morphologic alteration of the oviduct so that we could better understand its function. Many of these procedures were performed first in the human by necessity in order to overcome existing disease and/or to restore the continuity of the oviduct.8 They have been duplicated in experimental animals, especially the rabbit, in the more controlled setting of the laboratory. Simple transection and anastomosis of the oviduct performed microsurgically does not alter significantly subsequent fertility and tubal function. This has been demonstrated by numerous authors,9, 10 including ourselves,ll, 12 and in contradistinction to the work of Khoo and Mackay, 13 who performed the same experiment using conventional techniques and found a dramatic reduction in subsequent fertility. Morphologic modifications of the oviduct have been accomplished microsurgically by the excision of varying lengths of tube from different anatomic regions. The first such microsurgical experiment was performed by David et al.,14 who excised the UTJ in the rabbit and anastomosed the isthmus to the uterine horn. It is not my purpose to give here a detailed description of the various modifications performed by such authors as Patterson and Wood,9 Winston and Franzen,15 Eddy and co_workers,16-18 Halbert and Patton,19, 20 and Vol. 39, No.2, February 1983 Gomel An odyssey through the oviduct 145

3 McComb and Gomel.ll, 12, 21, 22 in our center. These modifications included the removal of the UTJ, the AIJ, the infundibulum, and varying lengths of isthmus or ampulla. They also included the reversal of an isthmic or ampullary segment, the vascular pedicle of which was preserved. Their observations have helped us to better understand oviductal function and the gamete transport mechanisms and arrive at the conclusions I have summarized earlier. They demonstrated, in addition, that the AIJ does not function independently and that the isthmus as a whole is responsible for ampullary ovum retention; that the oviduct can function albeit less efficiently despite a shortened isthmus or ampulla and, for that matter, despite the excision of the infundibular region; and most importantly, that the varying anatomic regions work together in remarkable concert, toward the optimal.function. RECENT SOCIOMEDICAL CHANGES Like the storms and other calamities faced by Ulysses, in the last two decades we have been perturbed by important sociomedical changes. There has been an epidemic of gonorrhea, with a proportional increase in salpingitis. This has paralleled the sexual liberation that occurred concomitantly. There has been a gradual increase in premarital sexual relations; for women, the percentage rose from 40% in 1965 to more than 65% in Sexually transmitted diseases have shown a fourfold increase in the United States in the same period of time. This has been accompanied not only by an increased incidence of salpingitis but also by a decrease in the mean age of its occurrence. The incidence of salpingitis in the age group between 15 and 24 rose to 1 in It has been estimated that close to one million women are treated for salpingitis in the United States each year and that more than one quarter of these are hospitalized. 24, 25 There has also been a significant increase in nongonococcal salpingitis. By culture of the organism from material obtained directly from the oviduct and/or by the substantial rise of serum antibody titers, Westrom 23 found the involvement of Chlamydia in 60% of cases of salpingitis. It is noteworthy that in a significant percentage of cases, salpingitis runs a less acute course than previously thought; only 10% of the patients presented with the classic picture of acute salpingitis. In approximately 60% of the infertility patients who present with bilateral hydrosalpinges, I have been unable to elicit a history of previous pelvic inflammatory disease (PID). The role ofchlamydia in these subclinical or subacute infections remains to be elucidated. 26 The widespread use of intrauterine devices (IUDs) and the associated infective potential has been another factor. Numerous recent studies have demonstrated that IUD users run a greater risk ofpid (varying between 1.7-fold to 9.3-fold), compared with nonusers. 27, 28 The increased risk of PID is especially evident among nulliparous women under 25 years of age. Salpingitis results in infertility in a significant percentage of the patients. Westrom 23 has shown that a single episode of salpingitis causes infertility in 11.4%, two episodes in 23.1%, and three or more episodes in 54.3% of the cases. Each subsequent episode appears to double the infertility rate. The chance for the occurrence of ectopic pregnancy increases sevenfold after one episode ofpid. After liberalization of the legislation governing abortion, the number of these procedures has increased geometrically. In the United States, close to 1,200,000 legally induced abortions were reported in A small percentage, but a significant number of these patients, have subsequent infertility due to complications of this procedure. The significant increase in the practice of contraception and legally induced abortions have resulted in the paucity of babies for adoption. In many instances they have also contributed to a delayed age of conception; the effect of this fact on the development of endometriosis and subsequent infertility remains to be elucidated. More than 800,000 elective tubal sterilizations are carried out in North America each year. Peterson and co-workers 30 noted a steady increase in the number of tubal sterilizations performed in non-federal, short-stay hospitals in the United States; these procedures rose from 200,000 in 1970 to 700,000 in The vast number of female sterilizations performed each year has created a problem of its own: the demand for reversal. These factors have led to a significant increase in infertility associated with tuboperitoneal factors and a marked decrease in the number of babies available for adoption, largely eliminating this long-employed alternative. Women became 146 Gomel An odyssey through the oviduct

4 more strongly motivated toward reconstructive infertility surgery and willing to accept a chance of success. that previously might have appeared too low. This was the background against which microsurgery was introduced into gynecology. 31 PERSONAL ODYSSEY My personal odyssey started soon after I completed my residency. I had vivid recollections of the frustration and disappointment I experienced at second laparotomies, undertaken to remove prosthetic devices left in situ, by the encounter of extensive adhesions: omentum, loops of bowel, internal genitalia "glued" together. Convinced that both the surgical technique and the results could be improved upon, I went to visit some of the leading centers of the time. What I saw in each instance was no different from what was practiced at home. The quest led me to the "promised land"-to the Sixth World Congress on Fertility and Sterility held in May During this meeting, it was my good fortune to meet Kurt Swolin, who was advocating a novel approach to salpingostomy, including the use of magnification. A few months later, I spent some time in Gothenburg with Swolin, to whom I wish to reiterate my gratitude here. He was employing the operating microscope and fine electrosurgical electrodes to excise periadnexal adhesions and to fashion a terminal salpingostomy, as I shall demonstrate later. Surprisingly, however, his approach to cornual occlusion was to perform a tubal implantation aided by a coronal incision on the uterine fundus. 32 -Upon returning to Vancouver, I commenced to use microsurgery and embarked on the development of techniques applicable to other tubal disorders. We were, I believe, the first to employ microsurgery in women for tubocornual and tubotubal anastomosis for both pathologic occlusions and for reversal of sterilization. This experience and that of salpingostomy for hydrosalpinx were presented at the Eighth World Congress on Fertility and Sterility held in Buenos Aires in It was a pleasant accident offate that the moderator of this session, Dr. Siegler, was sitting in the front row during that presentation. Whereas in Buenos Aires there were only one clinica1 33 and one experimental paper 34 presented on microsurgery, since 1976 there has been an explosive interest in infertility microsurgery, and many gynecologists have embraced this new discipline. PRINCIPLES OF MICROSURGERY The results associated with reconstructive infertility surgery were unsatisfactory and often disappointing in the past. Table I summarizes the collected results of the major published series that employed conventional surgical techniques. Among 347 cases of salpingoovariolysis, the term pregnancy rate was 41 %. The rate for 621 cases of salpingostomy was 13.2%. The term pregnancy rate among 429 cases of tubouterine implantation was 26.3%, and among 83 cases of tubotubal anastomosis for reversal of sterilization, it was 27.7%.26 Democritus said, "All that exists in the universe is the fruit of chance and of necessity." Indeed, microsurgical techniques were born into gynecology out of chance and of necessity. The principles include: (1) Atraumatic technique, in order to minimize intraperitoneal trauma and to decrease postoperative adhesions, which, in the past, were frequently the sole factor responsible for failure. (2) Irrigation of the exposed serosal surfaces to prevent dessication and to expose bleeding vessels. This is done with Ringer's lactate containing 5000 units of heparin per liter. Due to its anticoagulant property, heparin prevents fibrin formation; this is an important adjuvant in the prevention of postoperative adhesions. (3) Hemostasis is achieved by the electrocoagulation of the principal bleeding vessels with the use of a microelectrode to minimize the associated tissue destruction. (4) Complete excision of pathologic tissues. (5) Precise alignment and approximation of tissue planes. (6) Reperitonealization, which must be accomplished without ten- Table 1. Efficacy of Conventional Fertility SurgelJP No. of % Term % Ectopic Operation patients pregnancy pregnancy Salpingoovariolysis Salpingostomy Tubouterine im NS b plantation Tubotubal anasto NS mosis (sterilization reversal) afrom Gomel. 26 Reproduced with the permission of the publisher. bns, not stated. Vol. 39, No.2, February 1983 Gomel An odyssey through the oviduct 147

5 A B that may be excised. One thoroughly washes and wipes the gloves before commencing the surgery so as not to introduce foreign material into the peritoneal cavity. After appropriate hemostasis of the incision and entry into the peritoneal cavity, a wound protector is inserted and a Kirshner retractor applied. This low-profile instrument with four-way retraction provides excellent exposure. The bowel is transferred to the upper abdomen and kept in place with a large pad soaked in the irrigating solution. When present, periadnexal adhesions are divided at their lateral margin; and, once free, the uterus and adnexae are elevated by loosely packing the pouch of Douglas with Kerlex swabs also soaked in the heparinized irrigating solution. The patient is put into 10 to 15 Trendelenburg position and a similar degree of lateral tilt toward the surgeon. The microscope is brought into the operative field. 36 OPERATIVE TECHNIQUE Figure 1 Salpingostomy technique. (A), The terminal end of the distended hydrosalpinx is entered electrosurgically at the central avascular dimple. (B), The tip of a dropper is introduced into the opening, and the incision is extended over one of the avascular lines. (C), Working from the mucosal side, further incisions are made along the circumference of the tube, each following an avascular line. (D), A few interrupted sutures are placed to keep the stoma open. (From Gomel. 26 Reproduced with the permission of the publisher.) sion, since peritoneal ischemia causes adhesions. Large serosal defects are completely covered with a graft obtained from the peritoneum adjacent to the abdominal incision. These principles are not new. However, the use of (7) magnification enables the appreciation of the effects of trauma, albeit minimal. It permits the observation of both normal and pathologic morphologic details and proper application of the above principles. It further permits the use of appropriate microsurgical instruments and fine inert suture materials. 35, 36 With cases of reconstructive microsurgery, a Pfannenstiel incision is totally adequate unless the patient has a midline or a paramedian scar 148 Gomel An odyssey through the oviduct o SALPINGOOV ARIOLYSIS To achieve salpingoovariolysis, the adhesions are stretched and individually excised electrosurgically with the use of a microelectrode. Magnification enables the clear visualization of the demarcation line and the precise excision of the adhesions without injury to the tubal serosa or the ovarian surface, as the case may be. 37, 38 SALPINGOSTOMY The terminal end of the distended hydrosalpinx, under magnification, usually demonstrates a distinct vascular pattern that outlines a central dimple from which whitish avascular lines extend in a cartwheel manner. The tube is entered at the central dimple electrosurgically. The tip of a dropper is introduced into the opening created, the oviduct is distended again, and the incision is extended over one of the avascular lines. In this manner, a large enough opening is created that permits working from within the tube in order to complete the salpingostomy. Working from the mucosal side, the surgeon makes further incisions along the circumference of the tube, each following an avascular line. This permits the conservation of the ampullary mucosal folds, which will be shaped as the new fimbria. Proper dissection in this manner will also ensure the creation of a new fimbria ovarica. When avascular lines are followed, bleeding is usually negligible. A few inter-

6 Table 2. Results of Salpingostomy by Microsurgery Among 89 Patients a Followed for More than 1 Year" Result Not pregnant Spontaneous abortion Ectopic pregnancy Term pregnancy Total no. of patients No. of patients 52 4 C 8 d (9%) 28 (31.5%) afrom Gomel.26 Reproduced with the permission of the publisher. bthe 89 patients include 6 who were operated on the second time. "Two of these patients had term pregnancies as well. done of these patients had two subsequent term pregnancies. rupted sutures are used to keep the stoma open (Fig. 1). When ampullary mucosal folds are well preserved, under magnification, the new stoma has the appearance of a wild carnation. 3B, 39 Except for minor modifications, this is essentially the technique described by Swolin. In some cases, the terminal end of the oviduct is completely adherent to the ovary. In order to achieve a true terminal salpingostomy, one must first restore the physiologic relationship between the terminal end of the tube and the ovary. The oviduct is gently retracted and dissected free from the ovary electrosurgically. The portion of the ovary that was covered by the tube is thus exposed; and the tuboovarian ligament and the terminal end of the oviduct are freed. Terminal salpingostomy now becomes possible, performed with the use of the technique already described. The use of magnification and the described technique offer the following advantages. (1) They enable precise dissection of the distal portion of the oviduct from the ovary and the reestablishment of the physiologic relationships between these two organs. (2) They allow, in most cases, a terminal salpingostomy and the conservation of the whole oviduct. (3) They permit the shaping of a neostomy by incising over previously scarred areas, preserving intact the ampullary folds that will form the neofimbria. (4) Last, the procedure can be accomplished without any significant bleeding and without damage to the rich vascular supply of the terminal oviduct. 26 Active selection on my part was limited to only those cases with tuberculous salpingitis and severe adhesions bordering on a frozen pelvis. Among 89 patients followed for more than 1 year, a term pregnancy rate of 31.5% has been Vol. 39, No.2, February achieved. The ectopic pregnancy rate was 9% (Table 2).26 The ectopic pregnancy rate and the fact that 53% of our patients did not achieve any kind of pregnancy despite a morphologically satisfactory results are good indicators of the extent of tubal damage in these cases. TUBOCORNUAL ANASTOMOSIS Cornual occlusion of the oviduct has been traditionally treated by tubouterine implantation. This remains the predominant approach today. Ehrler,4o in 1965, published his observations that proximal pathologic occlusions rarely affect the intramural segment, which usually remains patent. It is remarkable that instead of a tubouterine implantation, he proposed and performed a tubocornual anastomosis for such cases, in defiance of the very narrow lumen of the interstitial tube «0.5 mm) and despite the lack of appropriate suture materials and magnification. Understandably, his results were disappointing. The cornual region of the uterus is injected in a circular fashion 0.5 cm from the UTJ with a mixture of dilute vasopressin and oxytocin. The serosa and superficial muscularis are incised, and the tube is transected at the level of the UTJ. Depending on the extent of the involvement of the intramural segment in the disease process, the tubocornual anastomosis may be juxtamural, in~... :: :.:. :..:.., :. ' '.- :....'...'.:". eo... : JUXTA-MURAL.. INTRA-MURAL JUXTA-UTERINE Figure 2 Tubocomual anastomosis. Depending on the extent of disease of the intramural segment, tubocomual anastomosis may be juxtamural, intramural, or juxtauterine. (From Gomel. 26 Reproduced with the permission of the publisher.) Gomel An odyssey through the oviduct 149

7 distal oviduct is assessed, and the pathologic isthmic segment is excised from the mesosalpinx electrosurgically. By keeping the excision line immediately adjacent to the tube, one avoids the transection of the tubal vessels. The muscularis is approximated with 8-0 Vicryl sutures placed at cardinal points, the first of which is inserted at the 6 o'clock position (Fig. 3). The recessed musculature of the interstitial oviduct often tests one's surgical skill in placing the sutures. After c Figure 3 Technique of tubocornual anastomosis. (A), The tube is transected at the level of the UTJ. Under high magnification, the cut surface is assessed, and the intramural segment is pared further until normal oviduct is encountered. (B), The pathologic isthmic segment is excised. The muscularis isapproximated with 8-0 Vicryl sutures placed at cardinal points. (C), The procedure is completed by the approximation of the serosa and the mesosalpinx. (From Gomel. 26 Reproduced with the permission of the publisher.) tramural, or juxtauterine (when most of the intramural segment requires excision and the anastomosis takes place very near or at the level of the uterine ostium) (Fig, 2).26 The intramural segment is pared further with the use of a curved cornual blade in order to avoid the creation of a large defect in the cornu. Patency is denoted by the free passage of the dye solution injected transcervically. High magnification, fine microsurgical instrumentation, and delicate suture materials are mandatory for the success of this operation. Higher magnifications allow proper assessment of the cut surfaces. The key to this procedure is the identification of healthy intramural oviduct. The 150 Gomel An odyssey through the oviduct Figure 4 Suturing technique for the approximation of the muscularis. (A and B), The first suture is placed at the 6 o'clock position on the mesenteric border of the tube, and it is tied. The subsequent sutures are placed at once with the same strand. The strand is then divided between the sutures, and each one is tied independently. (From Gomel. 26 Reproduced with the permission of the publisher.)

8 Table 3. Results of Tubocornual Anastomosis by Microsurgery for Pathologic Cornual Occlusion of the Oviducts Among 48 Patients Followed for More than 1 Year" Results Not pregnant Spontaneous abortion Ectopic pregnancy Term pregnancy Total no. of patients No. of patients 18 3 b 3c (6.2%) 27 (56.2%) afrom Gomel. 26 Reproduced with the permission of the publisher. ~o of these patients had term pregnancies as well. COne of these patients had a term pregnancy as well. placing the initial muscular suture at the 6 o'clock position, I usually place the subsequent three sutures at once with a single strand; the strand is then divided between the sutures, and each one is tied separately (Fig. 4). The serosa and superficial muscularis of the uterus is approximated next to the serosa of the tube with multiple interrupted sutures (Fig. 3).37,41 When the initial incision is made somewhat distal to the UTJ and the serosa and superficial muscularis dissected upward and preserved, at the completion of the anastomosis, the preserved seromuscular layer covers a short segment of proximal tube. In my series of tubocornual anastomosis for pathologic cornual occlusion, there were 48 pure cases, which are followed for more than 1 year. Twenty-seven of these achieved one or more term pregnancies, for a rate of 56.2% (Table 3).26 This is a microsurgical procedure, and it is technically more difficult to effect than the tubouterine implantation it replaces. However, it offers the distinct advantages of (1) maintaining the integrity of the uterine cornu and (2) preserving a longer oviduct. (3) It obviates the need for a cesarean section in the event of pregnancy and (4) yields better overall results. (5) Furthermore, in the event ofreocclusion, it permits a subsequent implantation. TUBOTUBAL ANASTOMOSIS Tubotubal anastomosis has become one of the more frequently performed reconstructive infertility operations. The procedure is largely performed for reversal of sterilization and rarely for cases of pathologic occlusion or with the aim of restoring fertility after segmental excision of an ectopic pregnancy. It may take the form of intra- 48 mural-isthmic, intramural-ampullary, isthmicisthmic, isthmic-ampullary, ampullary-ampullary, or ampullary-infundibular anastomosis. Time will not permit a detailed description of the technique for each. The basic technique is as follows. The tubal segments are measured for future analysis. Intraoperative transcervical chromopertubation distends the proximal tubal segments. The proximal stump is grasped with toothed forceps, slightly stretched, and the tube is transected with small, pointed, straight tubal scissors. The incision must stop at the mesosalpingeal margin and not extend into the mesosalpinx in order to avoid the division of the tubal vessels and prevent ischemia at the anastomosis site. The occluded end is then excised from the mesosalpinx electrosurgically. The cut surface ofthe oviduct is examined under high magnification to ascertain that it is free of disease. A normal oviduct is devoid of fibrosis and scarring; it has a normal muscular architecture, a pouting mucosa with typical folds, and a pristine vascular pattern. Hemostasis is achieved by the coagulation of the more significant bleeders. The distal stump is prepared, and then a two-layer anastomosis is performed. The muscularis is approximated with four or more interrupted sutures. Although the sutures spare the mucosa, they are placed submucosally in order to optimize mucosal aposition, since this layer is not approximated separately. The first suture is always placed at the 6 o'clock position and, as for all other sutures, in such a manner that the knot remains distal to the mucosa. Proper alignment of the two segments of tube is of great importance. The accurate placement of the first suture is therefore essential. The serosa is then approximated as a separate layer, and the mesosalpinx is joined (Fig. 5).37,42,43 For human surgery, tubal clamps and splints are not only unnecessary, but they may cause trauma if employed. In our series of reversal of sterilization requiring tubotubal anastomosis and comprising 118 patients followed for more than 18 months, 93 achieved one or more term pregnancies. This represents a rate of 78.8%. The ectopic pregnancy rate was under 2% (Table 4).26 It is essential to analyze cases of reversal of sterilization separate from those performed for pathologic conditions, since, in the majority of the reversal cases, the segments requiring anastomosis are essentially normal. Microsurgery in such cases permits (1) adequate debridement of the occluded ends without impairment of the blood Vol. 39, No.2, February 1983 Gomel An odyssey through the oviduct 151

9 B A Table 4. Results of Tubotubal Anastomosis by Microsurgery for Reversal of Sterilization in 118 Patients Followed for More than 18 Months a Results Not pregnant Ectopic pregnancy Intrauterine pregnancy Term pregnancy Total no. of patients No. of patients 20 2 (1.7%) 96 (81.4%) 93 (78.8%) 118 afrom Gome1. 26 Reproduced with the permission of the publisher. tion of the tissue planes with very fine synthetic sutures. The result is a normal, albeit shortened, oviduct. It is noteworthy that the tubal length of the reconstructed oviduct is an important factor in subsequent fertility. Whereas among the patients who had a reconstructed oviduct longer than 4 cm (as measured from the UTJ to the seromucous junction of the fimbriated end), the surgerypregnancy time interval was under 7 months, with those whose longer or single oviduct was under 4 cm in length, the mean time interval was 19.1 months (Table 5). Figure 5 Technique of tubotubal anastomosis. (A), The tubal stumps are debrided with small pointed tubal scissors. One must stop the transection short of the tubal vessels to avoid impairment of the vascular supply at the anastomosis site. (B and C), The muscularis is approximated with four or more interrupted 8-0 Vicryl sutures. (D), The procedure is completed by the approximation of the serosa and mesosalpinx. (From Gome1. 26 Reproduced with the permission of the publisher.) supply, (2) pinpoint hemostasis without unnecessary tissue destruction, (3) proper alignment of the tubal segments, and (4) accurate approxima- 152 Gomel An odyssey through the oviduct o LAPAROSCOPY Laparoscopy has been, and continues to be, a magnificent adventure in our odyssey. If infertility surgery has enjoyed markedly improved results, these results are not solely due to refinements in surgical techniques. Improvements in the methods and equipment for patient assessment have played a role in this regard. Whereas laparoscopy has attained its deserved recognition and place as a diagnostic tool, its value as an operative tool in infertility has, as yet, not been fully realized and remains in the domain of very few. Our primary approach to salpingoovariolysis and to the dilatation of fimbrial phimosis (fimbrioplasty) has been, whenever possible, laparoscopic surgery. Time will not permit a detailed description of these techniques. Stated briefly, adequate pneumoperitoneum and the Trendelenburg position keep the bowel out ofthe pelvis and enhance visibility. A uterine cannula permits transcervical intraoperative chromopertubation. A multiple puncture technique that separates the visual axis from the operative axis is essential to safety. In salpingoovariolysis, the aim is to excise the broad adhesions and to divide the lesser ones. The adhesions are exposed, stretched, and divided

10 Table 5. Mean Time Interval Between Surgery and Occurrence of Pregnancy After Microsurgical Tubotubal Anastomosis for Reversal of Sterilization a No. of Length of longer Mean time patients or only oviduct interval 82 >4cm cm or less Total series 10.2 afrom Gomel. 26 Reproduced with the permission of the publisher. one layer at a time close to the peritoneal surface or the ovary; this must be effected with great care in order not to damage the peritoneum or the ovarian surface. Thin velamentous adhesions are relatively avascular and are divided mechanically. Minute bleeding vessels stop spontaneously. Thicker, more vascular adhesions require coagulation before division. Space between structures is the key to safety.36, 44, 45 Broad adhesions are excised and removed through the ancillary trochar. Working methodically, the tube and ovary are completely freed. The pelvis is lavaged and, prior to the deflating of the abdomen, 150 ml of Ringer's lactate containing 250 mg of hydrocortisone succinate is left in the pelvis.26 Table 6 outlines a series of 92 cases of laparoscopic salpingoovariolysis, of which 14 required a fimbrioplasty as well. The adhesions were severe in the vast majority and moderate in the remainder. Moreover, only those cases where ovum pickup by the oviduct was deemed impossible or greatly hampered were included in the series. Fifty-seven patients (62%) achieved one or more intrauterine pregnancies. One half of these became pregnant within 6 months, and one quarter during the first two cycles that followed the surgery. Laparoscopic procedures offer many distinct advantages: (1) They may be performed during the initial diagnostic laparoscopy and (2) irrespective of the presence of other infertility factors, (3) they avoid a laparotomy, (4) they are associated with minimal discomfort, (5) the hospitalization is brief (most of these are done on a day-care basis), (6) the cost is markedly reduced, (7) the results have been satisfactory overall, and, furthermore, (8) this procedure does not preclude a future reconstructive operation by laparotomy if found to be necessary.26 ALTERNATIVE TECHNIQUES "Dawn comes early with rosy fingers." The clear of daylight demonstrates unequivocably mo that significantly better results can be achieved with the newer techniques I have reviewed. Similar results have been obtained by colleagues in this country and elsewhere. However, like Ulysses, we must not let ourselves be seduced by the sweet song of the sirens. We must consider the significant percentage of women for whom the goal of having a child is not achieved. This is especially true in cases of hydrosalpinx, where 53% of our patients achieved no pregnancy, even ectopic, despite the reestablishment of tubal patency and the restoration of pelvic morphology-in short, despite a satisfactory surgical outcome. There are those whose oviducts have been removed or irreparably damaged. Like Ulysses, we must try alternate routes, seek the help of other disciplines-the rapid ship of the noble Phaeacians that took Ulysses to his native Ithaca. Can we altogether bypass the oviduct? IN VITRO FERTILIZATION AND EMBRYO TRANSFER We are all aware of the valiant work of Steptoe and Edwards,46-48 Lopata and Johnston, 49 Wood and Trounson,50 and in this country Jones and Jones51 and the many co-workers in each group. In a normal or stimulated cycle, preovulatory oocytes are laparoscopically collected. They are incubated in an appropriate culture medium and fertilized by washed, incubated sperm. The culture is continued until the zygote has cleaved to between the 2-cell stage and the 8-cell stage, and then it is transferred to the mother. The results have improved gradually over the last 2 years. In the last 6 months, the Norfolk group attained a 20% implantation rate.51 These results will undoubtedly improve further in the future. In vitro fertilization and embryo transfer is becoming a credible alternative and may become the primary approach in many cir- Table 6. Salpingoovariolysis by Laparoscopya Outcome Term pregnancy Therapeutic abortion Spontaneous abortion Ectopic pregnancy Not pregnant Total no. of patients No. of patients (60.9%) afrom Gomel. 26 Reproduced with the permission of the publisher. bfour of the women with spontaneous abortions and two of thoile with ectopic pregnancies had term pregnancies as well. cfollowed for more than 9 months. 92 C Vol. 39, No.2, February 1983 Gomel An odyssey through the oviduct 153

11 cumstances. I have stressed, for example, that salpingostomy for hydrosalpinx has yielded relatively poor results, despite the fact that microsurgical techniques achieve morphologic reconstruction and tubal patency in an exceedingly high proportion of the cases. The irreversible damage suffered by the oviduct precludes pregnancy. Restoration of morphologic normality. does not always equate with restoration of function. In vitro fertilization may become the primary therapeutic approach for patients with hydrosalpinx when the ovaries are accessible and other cases of surgical failure. However, many will require an initial reconstructive microsurgical procedure to free the pelvic structures and render the ovaries more readily accessible to ovum recovery. The use of both therapeutic modalities (IVF and reconstructive microsurgery) may increase significantly the overall rate of pregnancy in many groups of patients. LOW OVUM TRANSFER Low ovum transfer has been explored as an alternative to reconstructive infertility surgery and in vitro fertilization. In this case, the preovulatory oocyte is aspirated and transferred into the ampullary segment of the fallopian tube. Kreitmann and Hodgen 52 successfully performed the procedure in rhesus monkeys. In our department, we are continuing to explore the value of this technique, using the rabbit as an animal model. In women, when the oviducts are terminally occluded secondary to endosalpingitis, this technique has the potential danger of being associated with a high-incidence ectopic pregnancy. The technique may have a place in patients with prior fimbriectomies. In many so-called fimbriectomies, the procedure is quite radical, leaving behind only a short segment of ampulla. Observations by Halbert et al.53, 54 in the rabbit have clearly demonstrated that the ability of the ampulla to apprehend ova markedly decreases as one moves gradually away from the fimbriated end. Only 5 of our 14 patients who had ampullary salpingostomy for reversal of fimbriectomy sterilization achieved term pregnancies, despite the fact that they were selected and, in each one of them, at least 50% of the ampulla was conserved. 26, 31 Fimbriectomy cases may lend themselves to low ovum transfer. This technique may in the future provide superior results in comparison with me- 154 Gomel An odyssey through the oviduct dioampullary salpingostomy and become an alternative therapeutic mode. PREVENTION OF INFERTILITY What we accept as reality is only our perception of it. That perception, I believe, is correct with regard to the superior results yielded by microsurgical techniques. It is also correct insofar as the many factors that lead to female infertility. PID is the single most important cause of female infertility. Furthermore, reconstructive microsurgery for the sequelae of this condition yields relatively poor results. 55 In acute salpingitis, subsequent infertility is directly related to delay in diagnosis and treatment. Especially in the young and nulliparous patient, a more liberal use of laparoscopy to establish the diagnosis and to institute early, effective treatment is preferable to a wait-and-see attitude. 31 We have mentioned such factors as intrauterine devices, abortion, and tubal sterilization. We have delineated a "risk population" with regard to the latter; this includes young women in their early reproductive years and those in an unstable marital relationship. Our findings further indicate that caution must be exercised in recommending puerperal sterilization to young women, especially those with low parity. Unless there is a specific medical indication, it is best to delay a sterilization procedure for 8 to 12 months and to employ other contraceptive measures in the interim. 56 In acute and subacute intraabdominal conditions, a more rational and liberal use of laparoscopy, including pediatric laparoscopy, permits early diagnosis and prompt treatment. This prevents complications associated with delayed diagnosis and helps avoid unnecessary laparotomies. 31 A significant proportion of women presenting with infertility due to tubal-peritoneal factors give a history of prior pelvic surgery. In the salpingoovariolysis series presented earlier, over 40% of the patients had had prior surgical operations (Table 7). In many of these, either the procedure was not required, or the indications were questionable, or the procedure that was performed was unnecessarily extensive. Frequently, the women suffered the undesirable sequelae of an operation either too extensive or too traumatic. 26 The assimilation of microsurgical principles and techniques into our specialty have made the

12 Table 7. Prior Pelvic Surgery Among 92 Patients Undergoing Laparoscopic Salpingoovariolysis a Nature of pelvic surgery Salpingo-oophorectomy Ovarian cystectomy Ovarian wedge resection Laparotomy Ectopic pregnancy Fimbrioplasty Salpingoovariolysis/salpingostomy Myomectomy Endometriosis Appendectomy Total with prior pelvic surgery No. of patients (43.5%) afrom Gomel. 26 Reproduced with the permission of the publisher. gynecologist much more aware of peritoneal trauma and more careful in tissue handling and tissue care. It has enabled the appreciation of normal and pathologic fine morphologic details. It has created a consciousness of conservation, the conservation of all possible healthy tissue; conservation that must be applied especially in a female child, adolescent, or woman desirous of remaining fertile; conservation that must be applied, whatever the nature of the pelvic pathology-ovarian cysts, endometriosis, ectopic pregnancy, pelvic inflammatory disease, even voluntary sterilization. The application of microsurgical principles to these cases will minimize postoperative adhesions and aid in the preservation of the morphologic normality of the pelvis. In the long term, this, I believe, will be the major impact and benefit of microsurgery in gynecology. ENVOI This has been a marvelous odyssey; I feel privileged and fortunate to have been one of the many travelers in this journey. The journey has yielded great rewards; yet the journey has not ended. Our appetite has been whetted, our senses stimulated, and our consciousness heightened. We have passed some lands and seen sites about which our perceptions may be incorrect, either because we crossed in darkness or because we have let our eyes be blinded by the blandishments of past experiences. We must go back and reassess; we must go forward and explore. Each man must act in that time which is his own. For us mortals, each individual odyssey comes to an abrupt end; for science, the odyssey continues. Acknowledgment. I would like to express my appreciation to Little, Brown and Co. for their permission to reproduce here text and illustrations from by book Microsurgery in Female Infertility, which is currently in press. REFERENCES 1. Homer: The Odyssey. Translation by W Shewring, New York, Oxford University Press, McKay WJS: History of Ancient Gynecology. London, Bailliere, Tindall and Cox, Daramberg CV: Oeuvres de Rufus d'ephese. Paris, L'Imprimerie Nationale, Fallopius G: Observationes Anatomicae. Venice, Blandau RJ: Comparative aspects of tubal anatomy and physiology as they relate to reconstructive procedures. J Reprod Med 21:7, Blandau RJ, Bourdage R, Halbert S: Tubal transport. In The Biology of the Fluids of the Female Genital Tract, Edited by FK Beller, GFB Schumacher. Amsterdam, Elsevier-North Holland, 1979, p Blandau RJ: The mechanism of ovulation and how eggs and sperm reach the site of fertilization. In Hormonal Contraceptives, Estrogens and Human Welfare, Edited by MC Diamond, CC Korenbrot. New York, Academic Press, 1978, p Gomel V: Tubal reanastomosis by microsurgery. Fertil Steril 28:59, Paterson P, Wood C: The use of microsurgery in the reanastomosis of the rabbit fallopian tube. Fertil Steril 25:757, Winston RML: Microsurgical reanastomosis of the rabbit oviduct and its functional and pathologic sequelae. Br J Obstet Gyrlaecol 82:513, McComb P, Gomel V: The influence of fallopian tube length on fertility in the rabbit. Fertil SteriI31:673, McComb P, Boer-Meisel M, Gomel V: The infiuenceof fallopian tube ampullary length on the fertility of the rabbit. Int J Fertil 26:30, Khoo SK, Mackay EV: Reactions in rabbit fallopian tube after plastic reconstruction. I. Gross pathology, tubal patency, and pregnancy. Fertil Steril 23:201, David A, Brackett BG, Garcia C: Effects of microsurgical removal of the rabbit uterotubal junction. Fertil Steril 20:250, Winston RML, Frantzen C, Oberti C: Oviduct function following resection of the ampullary-isthmic junction. Fertil Steril (Abstr) 28:284, Eddy CA: Tuboplastic microsurgery-appropriate sites for tube repair. In Reversibility of Female Sterilization, Edited by I Brosens, RML Winson. London, Academic Press, 1978, p Eddy CA, Antonini R Jr, Pauerstein CJ: Fertility following microsurgical removal of the ampullary-isthmic junction in rabbits. Fertil Steril 28:1090, Eddy CA, Hoffman JJ, Pauerstein CJ: Pregnancy following segmental isthmic reversal of the rabbit oviduct. Experientia 32:1194, Halbert SA, Patton DL: Egg transport in the rabbit oviduct following ampullary resection and microsurgical end-to-end anastomosis. Fertil Steril 32:687, Patton DL, Halbert SA: Electron microscopic examination of the rabbit oviductal ampulla following microsurgical end-to-end anastomosis. Fertil Steril 32:691, 1979 Vol. 39, No.2, February 1983 Gomel An odyssey through the oviduct 155

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