- Email: [email protected]
Infertility due to endometriosis
Infertility Conservative
DONALD
due to endornetriosis surgical
B. SPANGLER,
GEORGEANNA HOWARD Baltimore,
therapy
M.D.
S. JONES, W.
JONES,
JR.,
M.D. M.D.
Maryland
One hundred and one patients with endometriosis were treated with conservative operation because of infertility. Fifty-two patients followed at least one year subsequently conceived. Fifty-eight per cent of the 73 patients followed for 3 or more years achieved a pregnancy. A total of 87 conceptions occurred. The age of the patient at the time of operation, the duration of preoperative infertility, the patient’s previous parity, and the location of the disease did not appear to be significant factors in the results. Sixty per cent of the patients who conceived did so in the first year following operation. All but one of the patients who conceived did so within 3 years of the operation. Thirteen women required subsequent operation for symptomatic endometriosis; however, 5 of them had conceived.
ASSOCIATION between endometriosis and infertility is well known. Infertility has been estimated to be present in 40 to 50 per cent of patients with endometriosis.lpa In previous studies endometriosis was the only factor found to account for the infertility of 6 to 15 per cent of patients presenting with this complaint.3~4 While few will deny a close association, no one has yet been able to define the exact relationship that exists between endometriosis and infertility. Although nearly 50 years have passed since Sampson’s classic paperq598*7 speculation about the actual mechanism which renders these patients barren continues. Lack of knowledge prevents an accurate assessmentof the various
forms of treatment: estrogens, progestogens, androgens, and conservative operation. 9n the absenceof desirable double blind studies, clinical reports remain the major means of evaluating the effectiveness of a particular modality. This study deals with the resqlts of conservative surgical therapy and attempts to evaluate the factors contributing to the successes and failures of surgery among patients with endometriosis specifically complaining of infertility.
THE
Maferial
and
methods
The study includes patients operated upon at The Johns Hopkins Hospital from 1959 through 1968. All patients were married at the time of operation and had demonstrated infertility for at least one year prior to their operation. Only those patients who specifically expressed concern about i were included. One hundred and ve p&nnts, both “private” and “clinic,” f&lled thee criteria. Follow-up information Qould not be obtained on 4 patients and congruently
From the Department
of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine. Presented by invitation at the Eighty-first Annual Meeting of the American Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Sept. 10-12, 1970. 850
Volume Number
lo!3 6
the results listed are for the remaining 101 patients. The patients ranged from 20 to 42 years of age. The preoperative infertility varied from one to 13 years. All patients were followed for at least one year. The duration of follow-up varied from one to 10 years with a mean of 4.5 years. Seventythree patients were followed at least 3 years. The diagnosis of endometriosis was made on the basis of the history and physical examination in 84 patients. ,In 18 the diagnosis was confirmed by culdticopy. In three of the 84 cases the culdoscc)pic view was not confirmatory although endometriosis was subsequently noted at lapwotomy. In 6 patients the diagnosis was not suspected prior to the culdoscopic examin&on which established the presence of endometriosis. In 11 patients the diagnosis was made at celiotomy. In 5 of this group, previous culdoscopy failed to show the disease. In all the women the diagnosis was established at the operating table on the basis of the commonly accepted gross pathologic charaakeristics. In 65 of the patients where tissue removal was necessary, the operating room dihgnosis was confirmed by histopathologic exahination in the laboratory. In the remaining 86 patients destruction of the endometriosis was accomplished by fulguration to achieve minimal distortion. In these, tissue diagnosis was not possible. As noted above, the patients were selected because of the infertility associated with their endometriosis, hence the majority of these women had a complete infertility evaluation. This included a semen analysis, postcoital cervical mucus examination, timed endometrial biopsy, tubal patency check, and confirmation of ovulation. Culdoscopic visualization of the pelvis was utilized in 32 cases as noted above. A semen analysis was performed with the specimens of 77 of the patients’ husbands. The postcoital examination of cervical mucus was compltted in 72 of the cases. Of the 101 husbands involved, 87 were evaluated by at least obe of these methods. Ninety of the patients had an endometrial biopsy. Tubal patency evaluation by hysterosalpingogram, Rubin’b test, or
Infertility
due
to endometriosis
851
Table I. Age at time of operation Years 20-24 25-29 30-34 35-39 40 and
Patients 9 45 37 9 1
over
Table II. Duration operation Years 1-3 3-5 5-10 10 or more
Pregnant 5 24 19 4 0
of infertility
1 Patients 17 29 47
a
Per cent 56 53 51 44 0
prior to
1 Pregnant
) Percent
7
41 62 49 50
:: 4
visualization of spill of indigo carmine at culdoscopy was completed in 96 of the 101 cases. The occurrence of ovulation was confirmed in 96 of the patients. Endometriosis was the significant factor identified to account for the infertility of all 101 patients. It should be emphasized that in 64 of these patients with endometriosis, infertility was the only indication for operation. Results
Age at the time of operation. The patients’ ages at the time of operation ranged from 20 to 42 years. The mean age was 29.2 years. Table I presents the results according to age groups. The first four groups represent periods of 5 years. In the youngest group, aged 20 to 24, a 56 per cent pregnancy rate occurred. In the 10 patients over 35 a rate of 40 per cent was noted. Duration of infertility. The duration of preoperative infertility varied from one to 13 years. The mean duration was 5 years. The results, according to duration of infertility, are recorded in Table II. Type of infertility. Of the 101 patients in the study, 85 presented with primary infertility. Of these, 44 patients subsequently achieved a pregnancy. Of the 16 patients with secondary infertility, 13 had conceived only one time. Seven of these pregnancies ended in term deliv-
852
Spangler,
Table III:
Jones,
and
Location
March 15, 1971 Amer. J. Obstet. Gynec.
Jones
of disease Pregnant
Peritoneum Peritoneum Peritoneum One ovary Both ovaries Cul-de-sac Cul-de-sac
only and one and both
ovarv ovakes
involved not involved
Table IV. Comparison procedures
12 13 23 3
10 20 17 1
3: 13
3: 10
of several operative
Pregnant Uterine suspension No uterine suspension Presacral neurectomy No presacral neurectomy Appendectomy No appendectomy “Chocolate” spill No “chocolate” spill
Not pregnant
21 31 23 29 34 18
Not firegnant 15 34 14 35 32 17 7 42
cries; the rest terminated in abortion. Two patients of the secondary infertility group conceived twice and one patient was delivered of infants three times. This latter patient was delivered of one normal child, one child with bladder exstrophy, and one anencephalic infant who died 3 days after delivery. In this secondary infertility group of 16 patients, 8 became pregnant after their conservative surgery. Location of disease. Groupings of the various locations of the disease are found in Table III. At least one ovary was involved in all but ‘22 of the cases. These 22 patients did no better than the rest of the group as far as subsequent pregnancies were concerned. The 23 patients in whom the cul-desac was spared did not have a significantly higher pregnancy rate than the 78 patients with cul-de-sac involvement. Effects of various operative procedures. Various operative procedures were evaluated in an effort to uncover those which continually gave better results and those which decreased the chances for a later pregnancy. As is seen in Table IV, 21 of the 36 patients
who had a uterine suspension subsequently conceived. Of the 65 patients who had no uterine suspension, 31 were successful. Of the 37 patients who had a presacral neurectomy 23 conceived. Twenty-nine of the 64 patients without this procedure later became pregnant. Of the 10 patients who had an oophorectomy, 4 became pregnant while 6 did not. The question of whether or not to do an elective appendectomy at the time of operation done primarily for infertility is an ever-present one. In this series, 66 patients had an appendectomy at the time of the conservative operation, with 51.5 per cent of them subsequently becoming pregnant. Of those who did not have an appendectomy, 51.4 per cent conceived. “Chocolate” material was released into the pelvis from endometriomas ruptured during operation in 17 patients. Ten of them later became pregnant. Of the 84 patients with no “chocolate spill,” 42 conceived following the operation. Hormonal therapy. During the 10 year period included in this series, it was the custom of some physicians at our institution to give the infertile patient with endbmetriosis a trial period of “suppression” with methyltestosterone. Patients with successful use of this therapy do not appear in this series. Forty-one of the women in this operative series were treated unsuccessfully with this drug. Of the 41, 5 received postoperative testosterone therapy as well. Eighteen of this group achieved a pregnancy following operation. Of 5 patients receiving preoperative progestogen therapy, 2 conceived after operation. In the remaining 55 who received no preoperative therapy, 32 became pregnant postoperatively. Six of these 32 patients were given methyltestosterone and 2 received progestogens after operation. Length of time to first pregnancy. One of the primary reasons for .this review was to establish the Iength of time foIIowing the operation it would be reasonable to anticipate that the first pregnancy might occur. All 101 of the patients, as noted in Table V, were known to have been exposed to
Volume Number
109 6
pregnancy during the first year after operation. In this first year 32 patients, or 31.6 per cent of the group, conceived. Of the 69 patients remaining, 66 were known to be exposed during the first 2 years following operation. Thirteen patients, or 19.7 per cent of this group, achieved a pregnancy. Fourteen per cent, or 6 patients of the 43 known to be exposed during the first 3 years after operation became pregnant. Of the 27 women who were exposed for more than 3 years, one conceived 6 years after operation.
Infertility
Table V; Length first
to endometriosis
of time
from
853
operation
to
pregnancy Exposed
) Pregnant
101 66 43 27
32 13 6 1
First year ,,Second year ,;rThird year ,’ Beyond 3 years
Table VI. Age at operation
Yeari
Patients
1 Per cent 31.6 19.7 14.0 3.7
and duration of followed for
infertility in the 73 patients 3 or more years
Patients followed at least 3 years. ,$s noted above, essentially all the patients who conceived did so within the first 3 years following operation. In an attempt to eliminate as much as possible the prejudices of inadequate length of follow-up, the results for those patients followed at least 3 years were examined. There were 73 such patients. Forty-two women, or 58 per cent of the group, conceived. Forty patients were delivered of at least one live-born infant while 2 patients had their only pregnancy abort. These 73 patients were grouped according to ages at the time of operation and the duration of the preoperative infertility. The results are noted in Table VI. Subsequent operation. In an effort to evaluate the risks of conservative operation, the cases requiring a second operation were reviewed. Of the over-all group 13, or 12.8 per cent, had another operation because of symptomatic endometriosis. In 11 patients this included a hysterectomy. Five of the 11 conceived before the second procedure was necessary. In 2 additional women conservative operation was required, but not before one had conceived. Over-all pregnancy results. Of the 101 patients in the study, 52 subsequently became pregnant. At least one live-born infant was delivered of 47 of the women, while 4 patients had their only pregnancy abort. One first pregnancy was not completed at the time of this study. As noted in Table VII, a total of 87 conceptions occurred.
due
Pregnant
Per cent
Age 20-24 25-29 30-34 35-39
6 28 32 7
4 16 18 4
66 57 56 57
Duration of infertility 1-3 3-5 5..io 10 or more.
11 20 36 6
3 14 22 3
27 70 61 50
Table VII. patients operation
who
Pregnancy results conceived after
Total pregnancies Term Premature Abortion Not completed Ectopic
at time
of study
in the 52 conservative
87 66 5 11 5 0
Comment Endometriosis is a common disease with protean manifestations. Stevenson and Campbells indicated that a thorough history and physical examination will lead to the correct preoperative diagnosis in at least 80 per cent of cases. In this series the diagnosis was established in this manner in 84 of the patients. In 17 of the women, the diagnosis was not apparent until the pelvis was visualized. The discovery of plaques of endometriosis or adhesions secondary to this disease considerably improved the prognosis for these 17 infertile patients; the so-called “normal infertile couple” has a pregnancy
854
Spangler,
Jones, and Jones
expectancy of about 3 per cent.g No inf@rtility evaluation can be considered complgte until endometriosis has been ruled out by culdoscopic or laparoscopic visualization & the pelvis. In 1949, W. B. BaconlO one of the earliqt authors to support conservative oneratios, suggested that age at operation, duration 04 preoperative infertility, and location of &sease did not appear to alter the prognosis for future pregnancy. Subsequent authors have occasionally not agreed with some of his tenets. In 1966, GreenI reported a Rregnancy rate of 65 per cent for @ients aged 21 to 30, but contrasted this with a 31 per cent rate for patients aged 31 to 40 Ranneyi2 in 1970, noted that 42 of 48 infertility patients conceived after operation Only 7 of these 42 women were over 30 $n,nd none were over 35 years of age. Only 5 h&d been infer& more than 7 years and r&e of the 42 was infertile more than 10 years. The results of the present study seem to support Bacon’s opinions, with one unexplained exception. No statistically significant differences were noted among the pregnancy rates for the various age groups in both the over-all series and the patients followed for 3 years. A review of Table III indicates that the location of the disease did not significantly affect the chances for a pregnancy following operation. The duration of preoperative infertility was not a factor of success in the over-all group. In the group of 73 patients followed 3 years or more, however, those patients who were infertile for 3 years or less prior to operation did not do as well as the rest of the group. This result is unexplained. Green has stated that “the occurrence of does not increase the prior pregnancy chances of a successful outcome after a conservative operation.“ll The results of this series further substantiate that opinion. Of the patients presenting with primary infertility, 51.7 per cent achieved a pregnancy following operation. Fifty per cent of the secondary infertility group were successful. A few advocates of conservative surgery
Amer.
March 15, 1971 J. Obstet. Gynec.
have suggested that a uterine suspension and a presacral neurectomy be included as a routine part of all such operations.13 In this series more pregnant patients were noted in the groups who had either of these procedures than in their counterparts who did not. The differences were not significant enough to justify advocating a suspension or presacral neurectomy in all cases on this tptris, The success of conservative surgery in these infertile patients is defined in terms of the pregnancies. The time between operation and conception is full of hopeful anticipation for patient and physician alike. Of the 52 patients in this series who conceived, 61 per cent did so within the first year after operation. All but one of the pregnancies occurred within 3 years after the operation. These results are consistent with previous reports.ll’ 12, I3 On the weight of this evidence it seems justifiable to offer encouragement to the woman who has not conceived in the first year following her procedure. Equally important, the patient who does not achieve a pregnancy in 3 or 4 years should be advised to seek her family through adoption. Any discussion of conservative operation for endometriosis must include some consideration of the necessity for reoperation. Of the 101 patients in this series, 13 required additional operation because of endometriosis. For 5 of these women, the conservative operation could not be considered a “failure” because they conceived before the “second look” was required. The 51.4 per cent pregnancy rate in the over-all series and the 58 per cent rate in those patients followed at least 3 years compare favorably with the pregnancy rates of nonoperative series. The results of this review, along with others recently reported,llJ 121I3 indicate that conservative operation currently offers the infertile patient at least a 50 per cent chance of conceiving. On the basis of this evidence, conservative operative therapy remains the “treatment of choice” for the patient with infertility due to endometriosis.
Volume 109 Number 6
REFERENCES
1. Kistner, R. W.: In Behrman, S. J., and Kistner, R. W., editors: Progress in infertility, Boston, 1968, Little, Brown & Company, p. 331. 2. Te Linde, R. W., and Mattingly, R. F.: Operative Gynecology, ed. 4, Philadelphia and Toronto, 1970, J. B. Lippincott Company, p. 215. 3. Baeyertz, J. D.: Aust. N. Z. J. Obstet. Gynaec. 7: 204, 1967. 4. Jones, G. S., and Pourmand, K.: Fertil. Steril. 13: 398, 1962. 5. Sampson, J. A.: Arch. Surg. 3: 245, 1921. 6. Sampson, J. A.: AMER. J. OBSTET. GYNEC. 4: 451, 1922.
Discussion DR. ROBERT B. WILSON, Rochester, Minnesota. The authors have reported their results in 101 cases of infertility associated with endometriosis and have shown that 58 per cent of 73 of the patients in the series conceived after operative therapy. They found no discernible factor or factors that influenced the incidence of pregnancy after such therapy. That is, it made no difference how old the patient was, how long she had been infertile, or what part of her anatomy was involved-findings which imply that the patients had had endometriosis throughout their infertile years, that there was no other cause for the infertility, and that endometriosis was the sole cause of the infertile status of each. With a report such as this, every gynecologist who employs with enthusiasm the operative therapy of the infertile patient with endometriosis probably will use the 58 per cent success figure rather than a more reasonable one of 30 to 35 per cent when asked about the probability of pregnancy after such an operation. This lower figure represents 32 of the 52 patients (31.6 per cent) in this series who conceived during the first postoperative year. I believe the 31.6 per cent (and wonder if the authors agree) reflects more accurately the value of the procedure, because it is difficult to determine whether any type of therapy directed toward the correction of the infertile state has led to pregnancy and whether a therapeutic measure such as the one under discussion has been associated with pregnancies that occurred 2 or 3 years after treatment. As noted by the authors, their report concerns patients who complained of infertility. This leads to the obvious question as to whether there
Infertility
due to endometriosis
855
7. Sampson, J. A.: AMER. J. OBSTET. GYNEC. 14: 422, 1927. 8. Stevenson, C. S., and Campbell C. G.: Clin. Obstet. Gvnec. 3: 455. 1960. 9. Warner, M. P.: New York State J. Med. 62: 2665, 1962. 10. Bacon. W. B.: AMER. T. OBSTET. GYNEC. 57: 958, i949. 11. Green, T. H.: Clin. Obstet. Gynec. 9: 301, 1966. 12. Ranney, B.: AMER. .T. OBSTET. GYNEC. 107: 745, 19io. 13. Rogers, S. F., and Jacobs, W. M.: Fertil. Steril. 19: 530, 1968. ”
were other patients with endometriosis who were treated by operation, with preservation of their reproductive functions; and if so, what was the incidence of pregnancy in this group. One wonders also how many additional patients were scheduled for conservative therapy and, at laparotomy, were found to require hysterectomy, or more extensive operation. Would the authors agree that if such patients as these were included we would have a more accurate assessment of the value of this type of therapy? The authors have reported on the location of the disease, but they have not included data on its extent or the effect of the magnitude of involvement on the incidence of pregnancy. Inasmuch as the diagnosis was not made in 11 cases until the abdomen was opened and in an additional 6 until culdoscopy, and inasmuch as tissue removal was not required in 36 cases, one is led to the presumption that a significant number of patients had minimal disease. Do the authors, therefore, have additional information that would help determine which patients should be treated conservatively and whether operative therapy should be employed only in patients with limited disease--or should the conservatively treated group include patients whose disease requires resection of the bowel, resection of one or both ovaries, and removal of one tube, or in whom significant amounts of endometriosis must, because of its location, be left if some reproductive potential is to remain? The point of these doubts is that, although we at our institution are (for the most part) in full agreement with the choice of primary surgical therapy for cndometriosis, the results presented here might lead to unwarranted enthusi-
856
Spangler,
Jones,
and
March
Jones
asm and perhaps also could lead to unnecessary, unwarranted, or inadequate operation. Although not germane to the subject, the authors mention a report by Warner that the pregnancy expectancy is about 3 per cent in the “normal” infertile couple. In such patients, who have had standard investigation and advice, we have noted an incidence of pregnancy of 69 per cent. If one reads the article by Warner, the reasons for the discrepancy between these two percentages is apparent. However, the difference between the two is so great that I could not refrain from mentioning it. DR. S. LEON ISRAEL, Philadelphia, Pennsylvania. If it were the custom to grace such discussions with an epigraph, the words I would choose today would be from the presidential address of Joe Vincent Meigs-a name indissolubly linked to endometriosis-delivered to our Association from this lectern on Sept. 11, 1959: “Observation if the patient has no important symptoms is the proper treatment. However, if operation is to be undertaken, conservative treatment, that is, conservation of the uterus, tubes, and at least part of the ovaries, should always be the method of treatment in the young.“’ This fundamental concept was the tacit assumption made by Beechams in his early writings on this subject. It may also be considered the paradigm of the essayists’ presentation today. My role as a discusser is not to belabor their results-a 58 per cent pregnancy rate which stems from preservation of organ function-for certainly the major point of their thesis is not to be found in a statistical analysis. Whether one reaches the 51 per cent of conceptions achieved through conservative surgical means by Grays in 1960 or the 87.5 per cent attained recently by Ranney4 is irrelevant. No two series of infertile couples may be rightly compared unless they are closely matched in all clinical respects, particularly in regard to endometriosis as the sole cause of the involuntary barrenness. What is relevant is the salvage of childbearing capacity in the young woman as well as for the middle-aged one who desires it. Accordingly, I prefer to emphasize my interpretation of the basic aim of the Johns for Hopkins’ viewpoint : the ideal environment the conservative surgical treatment of endometriosis is provided best by a milieu ambiently designed to encourage fertility. It is important to recall that we are discussing neither the use of estrogen and progestin to achieve pseudopregnancy as a nonsurgical treatment of endometriosis nor the place of such
Amer.
J. Obstet.
15, 1971 Gynec.
hormones pre- and post-operatively. Nor are we ruminating upon “the riddle of the relationship between endometriosis and fertility,“6 particularly the mystification of its antifertility associations in the presence of both adequate tubal patency and cyclic ovulation. What was presented and is being discussed is the compelling theme that conservative management of endometriosis in younger women does not mean the avoidance of a surgical procedure but rather its performance in such a fashion that fertility is conserved. With this in mind, I believe that all inexplicably infertile women should be suspected of having endometriosis. They deserve laparoscopic confirmation of that suspicion and, when indicated, exploratory laparotomy. The term “exploratory” is used here to emphasize that the exploration involves only the decision of how much of the disordered tissue to excise and at the same time to preserve function. Finally, may I raise one question: In analyzing the value of the concomitant procedures of uterine suspension and presacral neurectomy, the essayists note that their results, somewhat better than equivocal, lean slightly in the affirmative direction. However, no mention was made of reefing, pleating, or shortening of the uteroovarian ligament, a step we have always employed following excision of an ovarian endometrioma. Do Drs. Jones and Spangler not use this surgical maneuver? REFERENCES
1. Meigs, J. V.: AMER. J. OBSTET. GYNEC. 79: 625, 1960. 2. Beecham, C. T.: J. A. M. A. 138: 971, 1949. 3. Gray, L. A.: Clin. Obstet. Gynec. 3: 472, 1960. 4. Ranney, B.: AMER. J. OBSTET. GYNEC. 107: 743,
1970.
5. Norwood, 1960.
G. E.: Clin. Obstet. Gynec. 3: 456,
DR. CLYDE RANDALL, Buffalo, New York. I wish to ask one question. Remembering that Dr. Meigs was impressed by and emphasized the significance of fixation-or at least decreased mobility-of the fimbriated portion of the tube, in the surgical management of your cases did you evaluate this ‘factor and did you make a particular effort to remedy such decreased mobility? Meigs seemed convinced that endometriosis did not account for occlusion of the tubes and that mere excision of demonstrable foci of endometriosis would not account for improved fertility after operation unless restoration of the mobility of the fimbria was also accomplished.
Volume 109 Number6
Has this seemed important in your experience? DR. JONES (Closing). Dr. Wilson asked whether it would be better to use the one-year rather than the three-year figure for the postoperative follow-up pregnancies. We were impressed by the fact that eventually no pregnancies occurred later than three years after an average infertile period of over 4 years and have rather felt for this reason that 3 years was a more realistic figure. We were delighted to have this figure of three years, because one of the questions patients always ask is when can they expect to get pregnant. At least in our own experience we feel confident now in saying that we are going to be hopeful for at least three years after operations. In this series, we have no data on patients who were operated upon for symptoms other than infertility. We do not know the fertility rate for that group of patients. There were no examples in this 101 patient study where conservative operation was attempted and had to be abandoned, for whatever reason. As to the extent of disease, we attempted to determine this and felt that the catalogue of involvement of ovaries and peritoneum, cul-desac, and so on was an indication of the extent of the disease. Perhaps a more accurate assay of the point was whether or not the patient had preoperative endocrine therapy. In discussing this point, we spoke about bulky en-
Infertility
due
to endometriosis
857
dometriosis as opposed to minimal endometriosis. In general, when we spoke of bulky endometriosis, we were speaking of endometriosis with ovaries fixed and enlarged, perhaps lyg times or more in size and with masses in the cul-de-sac which were greater than 2 or 3 cm. in diameter. Such patients, in our opinion, are not candidates for endocrine therapy. Thus, the patients in our series who had endocrine therapy may be considered to have had minimal endometriosis. The normal, infertile couple is always an interesting problem, and I am sure that with the passage of time and with the care of workup, the per cent of normal, infertile couples in any infertility practice decreases. In our own experience, I think the normal, infertile couple represents about 15 per cent. Dr. Israel asked about whether we used plication of the uteroovarian ligament. This was done in a small number of cases, but I can’t really give the exact figure. The surgical principle concerned is also involved with Dr. Randall’s question about tubal mobility. We attempted to preserve mobility of the tubes, feeling as do many people that this was of great importance in infertility. Likewise, as mentioned by Dr. Randall, we would thoroughly agree that tubal obstruction in endometriosis is an extraordinarily rare cause of infertility, and actually in the 101 cases mechanical obstruction of the tubes was specifically eliminated as a cause of the difficulty.
DONALD
due to endornetriosis surgical
B. SPANGLER,
GEORGEANNA HOWARD Baltimore,
therapy
M.D.
S. JONES, W.
JONES,
JR.,
M.D. M.D.
Maryland
One hundred and one patients with endometriosis were treated with conservative operation because of infertility. Fifty-two patients followed at least one year subsequently conceived. Fifty-eight per cent of the 73 patients followed for 3 or more years achieved a pregnancy. A total of 87 conceptions occurred. The age of the patient at the time of operation, the duration of preoperative infertility, the patient’s previous parity, and the location of the disease did not appear to be significant factors in the results. Sixty per cent of the patients who conceived did so in the first year following operation. All but one of the patients who conceived did so within 3 years of the operation. Thirteen women required subsequent operation for symptomatic endometriosis; however, 5 of them had conceived.
ASSOCIATION between endometriosis and infertility is well known. Infertility has been estimated to be present in 40 to 50 per cent of patients with endometriosis.lpa In previous studies endometriosis was the only factor found to account for the infertility of 6 to 15 per cent of patients presenting with this complaint.3~4 While few will deny a close association, no one has yet been able to define the exact relationship that exists between endometriosis and infertility. Although nearly 50 years have passed since Sampson’s classic paperq598*7 speculation about the actual mechanism which renders these patients barren continues. Lack of knowledge prevents an accurate assessmentof the various
forms of treatment: estrogens, progestogens, androgens, and conservative operation. 9n the absenceof desirable double blind studies, clinical reports remain the major means of evaluating the effectiveness of a particular modality. This study deals with the resqlts of conservative surgical therapy and attempts to evaluate the factors contributing to the successes and failures of surgery among patients with endometriosis specifically complaining of infertility.
THE
Maferial
and
methods
The study includes patients operated upon at The Johns Hopkins Hospital from 1959 through 1968. All patients were married at the time of operation and had demonstrated infertility for at least one year prior to their operation. Only those patients who specifically expressed concern about i were included. One hundred and ve p&nnts, both “private” and “clinic,” f&lled thee criteria. Follow-up information Qould not be obtained on 4 patients and congruently
From the Department
of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine. Presented by invitation at the Eighty-first Annual Meeting of the American Association of Obstetricians and Gynecologists, Hot Springs, Virginia, Sept. 10-12, 1970. 850
Volume Number
lo!3 6
the results listed are for the remaining 101 patients. The patients ranged from 20 to 42 years of age. The preoperative infertility varied from one to 13 years. All patients were followed for at least one year. The duration of follow-up varied from one to 10 years with a mean of 4.5 years. Seventythree patients were followed at least 3 years. The diagnosis of endometriosis was made on the basis of the history and physical examination in 84 patients. ,In 18 the diagnosis was confirmed by culdticopy. In three of the 84 cases the culdoscc)pic view was not confirmatory although endometriosis was subsequently noted at lapwotomy. In 6 patients the diagnosis was not suspected prior to the culdoscopic examin&on which established the presence of endometriosis. In 11 patients the diagnosis was made at celiotomy. In 5 of this group, previous culdoscopy failed to show the disease. In all the women the diagnosis was established at the operating table on the basis of the commonly accepted gross pathologic charaakeristics. In 65 of the patients where tissue removal was necessary, the operating room dihgnosis was confirmed by histopathologic exahination in the laboratory. In the remaining 86 patients destruction of the endometriosis was accomplished by fulguration to achieve minimal distortion. In these, tissue diagnosis was not possible. As noted above, the patients were selected because of the infertility associated with their endometriosis, hence the majority of these women had a complete infertility evaluation. This included a semen analysis, postcoital cervical mucus examination, timed endometrial biopsy, tubal patency check, and confirmation of ovulation. Culdoscopic visualization of the pelvis was utilized in 32 cases as noted above. A semen analysis was performed with the specimens of 77 of the patients’ husbands. The postcoital examination of cervical mucus was compltted in 72 of the cases. Of the 101 husbands involved, 87 were evaluated by at least obe of these methods. Ninety of the patients had an endometrial biopsy. Tubal patency evaluation by hysterosalpingogram, Rubin’b test, or
Infertility
due
to endometriosis
851
Table I. Age at time of operation Years 20-24 25-29 30-34 35-39 40 and
Patients 9 45 37 9 1
over
Table II. Duration operation Years 1-3 3-5 5-10 10 or more
Pregnant 5 24 19 4 0
of infertility
1 Patients 17 29 47
a
Per cent 56 53 51 44 0
prior to
1 Pregnant
) Percent
7
41 62 49 50
:: 4
visualization of spill of indigo carmine at culdoscopy was completed in 96 of the 101 cases. The occurrence of ovulation was confirmed in 96 of the patients. Endometriosis was the significant factor identified to account for the infertility of all 101 patients. It should be emphasized that in 64 of these patients with endometriosis, infertility was the only indication for operation. Results
Age at the time of operation. The patients’ ages at the time of operation ranged from 20 to 42 years. The mean age was 29.2 years. Table I presents the results according to age groups. The first four groups represent periods of 5 years. In the youngest group, aged 20 to 24, a 56 per cent pregnancy rate occurred. In the 10 patients over 35 a rate of 40 per cent was noted. Duration of infertility. The duration of preoperative infertility varied from one to 13 years. The mean duration was 5 years. The results, according to duration of infertility, are recorded in Table II. Type of infertility. Of the 101 patients in the study, 85 presented with primary infertility. Of these, 44 patients subsequently achieved a pregnancy. Of the 16 patients with secondary infertility, 13 had conceived only one time. Seven of these pregnancies ended in term deliv-
852
Spangler,
Table III:
Jones,
and
Location
March 15, 1971 Amer. J. Obstet. Gynec.
Jones
of disease Pregnant
Peritoneum Peritoneum Peritoneum One ovary Both ovaries Cul-de-sac Cul-de-sac
only and one and both
ovarv ovakes
involved not involved
Table IV. Comparison procedures
12 13 23 3
10 20 17 1
3: 13
3: 10
of several operative
Pregnant Uterine suspension No uterine suspension Presacral neurectomy No presacral neurectomy Appendectomy No appendectomy “Chocolate” spill No “chocolate” spill
Not pregnant
21 31 23 29 34 18
Not firegnant 15 34 14 35 32 17 7 42
cries; the rest terminated in abortion. Two patients of the secondary infertility group conceived twice and one patient was delivered of infants three times. This latter patient was delivered of one normal child, one child with bladder exstrophy, and one anencephalic infant who died 3 days after delivery. In this secondary infertility group of 16 patients, 8 became pregnant after their conservative surgery. Location of disease. Groupings of the various locations of the disease are found in Table III. At least one ovary was involved in all but ‘22 of the cases. These 22 patients did no better than the rest of the group as far as subsequent pregnancies were concerned. The 23 patients in whom the cul-desac was spared did not have a significantly higher pregnancy rate than the 78 patients with cul-de-sac involvement. Effects of various operative procedures. Various operative procedures were evaluated in an effort to uncover those which continually gave better results and those which decreased the chances for a later pregnancy. As is seen in Table IV, 21 of the 36 patients
who had a uterine suspension subsequently conceived. Of the 65 patients who had no uterine suspension, 31 were successful. Of the 37 patients who had a presacral neurectomy 23 conceived. Twenty-nine of the 64 patients without this procedure later became pregnant. Of the 10 patients who had an oophorectomy, 4 became pregnant while 6 did not. The question of whether or not to do an elective appendectomy at the time of operation done primarily for infertility is an ever-present one. In this series, 66 patients had an appendectomy at the time of the conservative operation, with 51.5 per cent of them subsequently becoming pregnant. Of those who did not have an appendectomy, 51.4 per cent conceived. “Chocolate” material was released into the pelvis from endometriomas ruptured during operation in 17 patients. Ten of them later became pregnant. Of the 84 patients with no “chocolate spill,” 42 conceived following the operation. Hormonal therapy. During the 10 year period included in this series, it was the custom of some physicians at our institution to give the infertile patient with endbmetriosis a trial period of “suppression” with methyltestosterone. Patients with successful use of this therapy do not appear in this series. Forty-one of the women in this operative series were treated unsuccessfully with this drug. Of the 41, 5 received postoperative testosterone therapy as well. Eighteen of this group achieved a pregnancy following operation. Of 5 patients receiving preoperative progestogen therapy, 2 conceived after operation. In the remaining 55 who received no preoperative therapy, 32 became pregnant postoperatively. Six of these 32 patients were given methyltestosterone and 2 received progestogens after operation. Length of time to first pregnancy. One of the primary reasons for .this review was to establish the Iength of time foIIowing the operation it would be reasonable to anticipate that the first pregnancy might occur. All 101 of the patients, as noted in Table V, were known to have been exposed to
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pregnancy during the first year after operation. In this first year 32 patients, or 31.6 per cent of the group, conceived. Of the 69 patients remaining, 66 were known to be exposed during the first 2 years following operation. Thirteen patients, or 19.7 per cent of this group, achieved a pregnancy. Fourteen per cent, or 6 patients of the 43 known to be exposed during the first 3 years after operation became pregnant. Of the 27 women who were exposed for more than 3 years, one conceived 6 years after operation.
Infertility
Table V; Length first
to endometriosis
of time
from
853
operation
to
pregnancy Exposed
) Pregnant
101 66 43 27
32 13 6 1
First year ,,Second year ,;rThird year ,’ Beyond 3 years
Table VI. Age at operation
Yeari
Patients
1 Per cent 31.6 19.7 14.0 3.7
and duration of followed for
infertility in the 73 patients 3 or more years
Patients followed at least 3 years. ,$s noted above, essentially all the patients who conceived did so within the first 3 years following operation. In an attempt to eliminate as much as possible the prejudices of inadequate length of follow-up, the results for those patients followed at least 3 years were examined. There were 73 such patients. Forty-two women, or 58 per cent of the group, conceived. Forty patients were delivered of at least one live-born infant while 2 patients had their only pregnancy abort. These 73 patients were grouped according to ages at the time of operation and the duration of the preoperative infertility. The results are noted in Table VI. Subsequent operation. In an effort to evaluate the risks of conservative operation, the cases requiring a second operation were reviewed. Of the over-all group 13, or 12.8 per cent, had another operation because of symptomatic endometriosis. In 11 patients this included a hysterectomy. Five of the 11 conceived before the second procedure was necessary. In 2 additional women conservative operation was required, but not before one had conceived. Over-all pregnancy results. Of the 101 patients in the study, 52 subsequently became pregnant. At least one live-born infant was delivered of 47 of the women, while 4 patients had their only pregnancy abort. One first pregnancy was not completed at the time of this study. As noted in Table VII, a total of 87 conceptions occurred.
due
Pregnant
Per cent
Age 20-24 25-29 30-34 35-39
6 28 32 7
4 16 18 4
66 57 56 57
Duration of infertility 1-3 3-5 5..io 10 or more.
11 20 36 6
3 14 22 3
27 70 61 50
Table VII. patients operation
who
Pregnancy results conceived after
Total pregnancies Term Premature Abortion Not completed Ectopic
at time
of study
in the 52 conservative
87 66 5 11 5 0
Comment Endometriosis is a common disease with protean manifestations. Stevenson and Campbells indicated that a thorough history and physical examination will lead to the correct preoperative diagnosis in at least 80 per cent of cases. In this series the diagnosis was established in this manner in 84 of the patients. In 17 of the women, the diagnosis was not apparent until the pelvis was visualized. The discovery of plaques of endometriosis or adhesions secondary to this disease considerably improved the prognosis for these 17 infertile patients; the so-called “normal infertile couple” has a pregnancy
854
Spangler,
Jones, and Jones
expectancy of about 3 per cent.g No inf@rtility evaluation can be considered complgte until endometriosis has been ruled out by culdoscopic or laparoscopic visualization & the pelvis. In 1949, W. B. BaconlO one of the earliqt authors to support conservative oneratios, suggested that age at operation, duration 04 preoperative infertility, and location of &sease did not appear to alter the prognosis for future pregnancy. Subsequent authors have occasionally not agreed with some of his tenets. In 1966, GreenI reported a Rregnancy rate of 65 per cent for @ients aged 21 to 30, but contrasted this with a 31 per cent rate for patients aged 31 to 40 Ranneyi2 in 1970, noted that 42 of 48 infertility patients conceived after operation Only 7 of these 42 women were over 30 $n,nd none were over 35 years of age. Only 5 h&d been infer& more than 7 years and r&e of the 42 was infertile more than 10 years. The results of the present study seem to support Bacon’s opinions, with one unexplained exception. No statistically significant differences were noted among the pregnancy rates for the various age groups in both the over-all series and the patients followed for 3 years. A review of Table III indicates that the location of the disease did not significantly affect the chances for a pregnancy following operation. The duration of preoperative infertility was not a factor of success in the over-all group. In the group of 73 patients followed 3 years or more, however, those patients who were infertile for 3 years or less prior to operation did not do as well as the rest of the group. This result is unexplained. Green has stated that “the occurrence of does not increase the prior pregnancy chances of a successful outcome after a conservative operation.“ll The results of this series further substantiate that opinion. Of the patients presenting with primary infertility, 51.7 per cent achieved a pregnancy following operation. Fifty per cent of the secondary infertility group were successful. A few advocates of conservative surgery
Amer.
March 15, 1971 J. Obstet. Gynec.
have suggested that a uterine suspension and a presacral neurectomy be included as a routine part of all such operations.13 In this series more pregnant patients were noted in the groups who had either of these procedures than in their counterparts who did not. The differences were not significant enough to justify advocating a suspension or presacral neurectomy in all cases on this tptris, The success of conservative surgery in these infertile patients is defined in terms of the pregnancies. The time between operation and conception is full of hopeful anticipation for patient and physician alike. Of the 52 patients in this series who conceived, 61 per cent did so within the first year after operation. All but one of the pregnancies occurred within 3 years after the operation. These results are consistent with previous reports.ll’ 12, I3 On the weight of this evidence it seems justifiable to offer encouragement to the woman who has not conceived in the first year following her procedure. Equally important, the patient who does not achieve a pregnancy in 3 or 4 years should be advised to seek her family through adoption. Any discussion of conservative operation for endometriosis must include some consideration of the necessity for reoperation. Of the 101 patients in this series, 13 required additional operation because of endometriosis. For 5 of these women, the conservative operation could not be considered a “failure” because they conceived before the “second look” was required. The 51.4 per cent pregnancy rate in the over-all series and the 58 per cent rate in those patients followed at least 3 years compare favorably with the pregnancy rates of nonoperative series. The results of this review, along with others recently reported,llJ 121I3 indicate that conservative operation currently offers the infertile patient at least a 50 per cent chance of conceiving. On the basis of this evidence, conservative operative therapy remains the “treatment of choice” for the patient with infertility due to endometriosis.
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REFERENCES
1. Kistner, R. W.: In Behrman, S. J., and Kistner, R. W., editors: Progress in infertility, Boston, 1968, Little, Brown & Company, p. 331. 2. Te Linde, R. W., and Mattingly, R. F.: Operative Gynecology, ed. 4, Philadelphia and Toronto, 1970, J. B. Lippincott Company, p. 215. 3. Baeyertz, J. D.: Aust. N. Z. J. Obstet. Gynaec. 7: 204, 1967. 4. Jones, G. S., and Pourmand, K.: Fertil. Steril. 13: 398, 1962. 5. Sampson, J. A.: Arch. Surg. 3: 245, 1921. 6. Sampson, J. A.: AMER. J. OBSTET. GYNEC. 4: 451, 1922.
Discussion DR. ROBERT B. WILSON, Rochester, Minnesota. The authors have reported their results in 101 cases of infertility associated with endometriosis and have shown that 58 per cent of 73 of the patients in the series conceived after operative therapy. They found no discernible factor or factors that influenced the incidence of pregnancy after such therapy. That is, it made no difference how old the patient was, how long she had been infertile, or what part of her anatomy was involved-findings which imply that the patients had had endometriosis throughout their infertile years, that there was no other cause for the infertility, and that endometriosis was the sole cause of the infertile status of each. With a report such as this, every gynecologist who employs with enthusiasm the operative therapy of the infertile patient with endometriosis probably will use the 58 per cent success figure rather than a more reasonable one of 30 to 35 per cent when asked about the probability of pregnancy after such an operation. This lower figure represents 32 of the 52 patients (31.6 per cent) in this series who conceived during the first postoperative year. I believe the 31.6 per cent (and wonder if the authors agree) reflects more accurately the value of the procedure, because it is difficult to determine whether any type of therapy directed toward the correction of the infertile state has led to pregnancy and whether a therapeutic measure such as the one under discussion has been associated with pregnancies that occurred 2 or 3 years after treatment. As noted by the authors, their report concerns patients who complained of infertility. This leads to the obvious question as to whether there
Infertility
due to endometriosis
855
7. Sampson, J. A.: AMER. J. OBSTET. GYNEC. 14: 422, 1927. 8. Stevenson, C. S., and Campbell C. G.: Clin. Obstet. Gvnec. 3: 455. 1960. 9. Warner, M. P.: New York State J. Med. 62: 2665, 1962. 10. Bacon. W. B.: AMER. T. OBSTET. GYNEC. 57: 958, i949. 11. Green, T. H.: Clin. Obstet. Gynec. 9: 301, 1966. 12. Ranney, B.: AMER. .T. OBSTET. GYNEC. 107: 745, 19io. 13. Rogers, S. F., and Jacobs, W. M.: Fertil. Steril. 19: 530, 1968. ”
were other patients with endometriosis who were treated by operation, with preservation of their reproductive functions; and if so, what was the incidence of pregnancy in this group. One wonders also how many additional patients were scheduled for conservative therapy and, at laparotomy, were found to require hysterectomy, or more extensive operation. Would the authors agree that if such patients as these were included we would have a more accurate assessment of the value of this type of therapy? The authors have reported on the location of the disease, but they have not included data on its extent or the effect of the magnitude of involvement on the incidence of pregnancy. Inasmuch as the diagnosis was not made in 11 cases until the abdomen was opened and in an additional 6 until culdoscopy, and inasmuch as tissue removal was not required in 36 cases, one is led to the presumption that a significant number of patients had minimal disease. Do the authors, therefore, have additional information that would help determine which patients should be treated conservatively and whether operative therapy should be employed only in patients with limited disease--or should the conservatively treated group include patients whose disease requires resection of the bowel, resection of one or both ovaries, and removal of one tube, or in whom significant amounts of endometriosis must, because of its location, be left if some reproductive potential is to remain? The point of these doubts is that, although we at our institution are (for the most part) in full agreement with the choice of primary surgical therapy for cndometriosis, the results presented here might lead to unwarranted enthusi-
856
Spangler,
Jones,
and
March
Jones
asm and perhaps also could lead to unnecessary, unwarranted, or inadequate operation. Although not germane to the subject, the authors mention a report by Warner that the pregnancy expectancy is about 3 per cent in the “normal” infertile couple. In such patients, who have had standard investigation and advice, we have noted an incidence of pregnancy of 69 per cent. If one reads the article by Warner, the reasons for the discrepancy between these two percentages is apparent. However, the difference between the two is so great that I could not refrain from mentioning it. DR. S. LEON ISRAEL, Philadelphia, Pennsylvania. If it were the custom to grace such discussions with an epigraph, the words I would choose today would be from the presidential address of Joe Vincent Meigs-a name indissolubly linked to endometriosis-delivered to our Association from this lectern on Sept. 11, 1959: “Observation if the patient has no important symptoms is the proper treatment. However, if operation is to be undertaken, conservative treatment, that is, conservation of the uterus, tubes, and at least part of the ovaries, should always be the method of treatment in the young.“’ This fundamental concept was the tacit assumption made by Beechams in his early writings on this subject. It may also be considered the paradigm of the essayists’ presentation today. My role as a discusser is not to belabor their results-a 58 per cent pregnancy rate which stems from preservation of organ function-for certainly the major point of their thesis is not to be found in a statistical analysis. Whether one reaches the 51 per cent of conceptions achieved through conservative surgical means by Grays in 1960 or the 87.5 per cent attained recently by Ranney4 is irrelevant. No two series of infertile couples may be rightly compared unless they are closely matched in all clinical respects, particularly in regard to endometriosis as the sole cause of the involuntary barrenness. What is relevant is the salvage of childbearing capacity in the young woman as well as for the middle-aged one who desires it. Accordingly, I prefer to emphasize my interpretation of the basic aim of the Johns for Hopkins’ viewpoint : the ideal environment the conservative surgical treatment of endometriosis is provided best by a milieu ambiently designed to encourage fertility. It is important to recall that we are discussing neither the use of estrogen and progestin to achieve pseudopregnancy as a nonsurgical treatment of endometriosis nor the place of such
Amer.
J. Obstet.
15, 1971 Gynec.
hormones pre- and post-operatively. Nor are we ruminating upon “the riddle of the relationship between endometriosis and fertility,“6 particularly the mystification of its antifertility associations in the presence of both adequate tubal patency and cyclic ovulation. What was presented and is being discussed is the compelling theme that conservative management of endometriosis in younger women does not mean the avoidance of a surgical procedure but rather its performance in such a fashion that fertility is conserved. With this in mind, I believe that all inexplicably infertile women should be suspected of having endometriosis. They deserve laparoscopic confirmation of that suspicion and, when indicated, exploratory laparotomy. The term “exploratory” is used here to emphasize that the exploration involves only the decision of how much of the disordered tissue to excise and at the same time to preserve function. Finally, may I raise one question: In analyzing the value of the concomitant procedures of uterine suspension and presacral neurectomy, the essayists note that their results, somewhat better than equivocal, lean slightly in the affirmative direction. However, no mention was made of reefing, pleating, or shortening of the uteroovarian ligament, a step we have always employed following excision of an ovarian endometrioma. Do Drs. Jones and Spangler not use this surgical maneuver? REFERENCES
1. Meigs, J. V.: AMER. J. OBSTET. GYNEC. 79: 625, 1960. 2. Beecham, C. T.: J. A. M. A. 138: 971, 1949. 3. Gray, L. A.: Clin. Obstet. Gynec. 3: 472, 1960. 4. Ranney, B.: AMER. J. OBSTET. GYNEC. 107: 743,
1970.
5. Norwood, 1960.
G. E.: Clin. Obstet. Gynec. 3: 456,
DR. CLYDE RANDALL, Buffalo, New York. I wish to ask one question. Remembering that Dr. Meigs was impressed by and emphasized the significance of fixation-or at least decreased mobility-of the fimbriated portion of the tube, in the surgical management of your cases did you evaluate this ‘factor and did you make a particular effort to remedy such decreased mobility? Meigs seemed convinced that endometriosis did not account for occlusion of the tubes and that mere excision of demonstrable foci of endometriosis would not account for improved fertility after operation unless restoration of the mobility of the fimbria was also accomplished.
Volume 109 Number6
Has this seemed important in your experience? DR. JONES (Closing). Dr. Wilson asked whether it would be better to use the one-year rather than the three-year figure for the postoperative follow-up pregnancies. We were impressed by the fact that eventually no pregnancies occurred later than three years after an average infertile period of over 4 years and have rather felt for this reason that 3 years was a more realistic figure. We were delighted to have this figure of three years, because one of the questions patients always ask is when can they expect to get pregnant. At least in our own experience we feel confident now in saying that we are going to be hopeful for at least three years after operations. In this series, we have no data on patients who were operated upon for symptoms other than infertility. We do not know the fertility rate for that group of patients. There were no examples in this 101 patient study where conservative operation was attempted and had to be abandoned, for whatever reason. As to the extent of disease, we attempted to determine this and felt that the catalogue of involvement of ovaries and peritoneum, cul-desac, and so on was an indication of the extent of the disease. Perhaps a more accurate assay of the point was whether or not the patient had preoperative endocrine therapy. In discussing this point, we spoke about bulky en-
Infertility
due
to endometriosis
857
dometriosis as opposed to minimal endometriosis. In general, when we spoke of bulky endometriosis, we were speaking of endometriosis with ovaries fixed and enlarged, perhaps lyg times or more in size and with masses in the cul-de-sac which were greater than 2 or 3 cm. in diameter. Such patients, in our opinion, are not candidates for endocrine therapy. Thus, the patients in our series who had endocrine therapy may be considered to have had minimal endometriosis. The normal, infertile couple is always an interesting problem, and I am sure that with the passage of time and with the care of workup, the per cent of normal, infertile couples in any infertility practice decreases. In our own experience, I think the normal, infertile couple represents about 15 per cent. Dr. Israel asked about whether we used plication of the uteroovarian ligament. This was done in a small number of cases, but I can’t really give the exact figure. The surgical principle concerned is also involved with Dr. Randall’s question about tubal mobility. We attempted to preserve mobility of the tubes, feeling as do many people that this was of great importance in infertility. Likewise, as mentioned by Dr. Randall, we would thoroughly agree that tubal obstruction in endometriosis is an extraordinarily rare cause of infertility, and actually in the 101 cases mechanical obstruction of the tubes was specifically eliminated as a cause of the difficulty.