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Infertility following wedge resection of the ovaries
Infertility
following
wedge resection of the ovaries
R. TOAFF M. E. TOAFF M. R. PEYSER Tel-Aviv,
Israel
Seven cases of polycystic ovarian disuse were investigated by !aparoscopr and rndocrinologic tests after failure of ovarian resech.@nto restore fertility. One case of bilateral and two cases of unilateral ovarian atrophy were recorded. In all seven patients the common features were extensive periovarian and pitubal adhesions. Four of the six patients amenable to cure were submitted to reconstructive surgery; three of them conceived and had normal deliveries. The present observations suppOrt the pka to relegate tk surgical approach to a minor position in patients with Stein-Leventhal syndrome and stress the importance of meticulous surgicak technique in the performance of ovarian surgery. Laparoscopic investigation is mandatory in all cases of unsuccessful ovarian resection.
DESPITE the growing interest in conservative methods for induction of ovulation in polycystic ovarian disease, wedge resection of the ovaries is still very much in use. Its beneficial effects are well documented. According to Goldzieher’s’ survey of published results, regular cycles follow surgery in 80 per cent of patients and desired pregnancy is achieved in 63 per cent. In some series, however, less than 10 per cent of subjects experienced regulation of menses and only 13 per cent conceived.2 It is generally agreed that fertility is restored less often than the menstrual rhythm.‘, 3 Questionable diagnosis and surgical complications may be involved in the failure of ovarian wedge resection to achieve its aim. The present report describes a series of seven cases of polycystic ovarian disease submitted to laparoscopic and endocrinologic investigations after the failure of surgery to restore fertility.
Stein-Leventhal syndrome, were investigated. Their complaint was persistent sterility, with or without obvious menstrual disorders. Four of them, whose operation records showed that at operation other pathology, such as malformations, tumors, or sequelae of pelvic inflammatory disease, was found beside polycystic ovaries, were not included in the present series in spite of similar findings. Six of the seven patients of the series were 26 to 28 years of age and one was 39. Ovarian surgery had been performed 2 to 9 years previously. All the patients had been treated, after endocrine studies were carried out before and after surgery, in different institutions and by private practitioners. As reliable data were not available in most cases, however, only information known to the patient and surgical records were used in establishing the early history. The investigations performed included the following. (1) Endocrine evaluation, including 17-ketosteroid excretion and their fractionation, adrenocortical suppression and ovarian stimulation (dexamethasoneHCG test according to Jayle*) plasma LH studies under basic conditions and after clomiphene administration, estrogen excretion, evaluation of thyroid function. (2) Hysterosalpingography with water-soluble contrast medium. (3) Laparoscopy, generally within 2 to 4 days after occurrence of the thermal shift in clomiphenetreated cycles.
Material and methods During a 6 year period (1967-1972) 11 women, who had previously been submitted to wedge resection of the ovaries in other hospitals with diagnosis of From the Department of Obstetrics and Gynecology ‘;4,” Hakilyah Matmnity Hospitnl, Municipal-Governmental Medical Center, Tel-Aviv University School of Medicine. Received
for publication
Revtied January Accepted Januq
September
24, 1974.
16, 1975. 16, 1975.
Reprint requests: R. Toaff, Tel-Aviv, Israel
M.D.,
Case 1. A. B., 27 years of age, sought secondary sterility and oligomenorrhea.
P. 0. Box 7079,
92
advice for Following
Volume Number
124 1
menarche at 13, she had normal periods for 3 days’ duration every 30 days up to the age of 21. Married at 17, she had at 19 a normal pregnancy and delivery. For the last 6 years she menstruated for 10 days every 45 to 60 days and she could not conceive. In 1965, at the age of 25, following culdoscopic examination which revealed enlarged, white, smooth ovaries, she was submitted to bilateral ovarian resection. The postoperative course was complicated by fever and abdominal pains. The menstrual rhythm remained unchanged and no conception followed. On examination, no physical abnormalities were observed. The endocrine findings were within normal limits. At laparoscopy, abundant pelvic peritoneal adhesions were found. The left adnexae were included in a single fibrotic mass. The right ovary was slightly enlarged, micropolycystic, and partially covered by the adherent, distorted tube. The patient was operated on again in 1967. The left ovary was reduced to a fibrotic band. The right ovary was freed from its extensive adhesions to the tube, the posterior wall of the uterus, and broad ligament. The peritoneal lining of the right tube was carefully reconstructed. The postoperative course was uneventful. One year later the patient conceived under clomiphene treatment (500 mg. per cycle, five cycles) and had a normal term delivery. Case 2. S. M., 28 years of age, had been married 8 years when first seen. Since menarche at the age of 10, she had menstruated 4 to 5 days every 1 to 4 months. For that reason she had been submitted to bilateral ovarian resection at the age of 19, shortly before marriage, in 1962. After operation she had normal menses for 3 years, followed by recurrence of oligomenorrhea. She was never pregnant. On physical examination, no endocrine stigmas were recorded. The only positive finding at endocrine evaluation was hypothyroidism. Her LH plasma values were 20 to 24 mU per milliliter. Under thyroxine treatment (100 Fg per day) her periods became regular, but were apparently anovulatory. At laparoscopy, a few months later, dense peritubal and periovarian adhesions were seen. The patient underwent reconstructive surgery in December, 1971. Both ovaries were enlarged and polycystic, almost completely covered by adhesions involving omentum and tubes. The distal part of the left tube was completely buried by adhesions deep into the pelvis. The left tube was only partially covered by adhesions, but the fimbriae were almost completely adherent to the ovarian surface. Following careful reconstruction and endocrine treatment which included thyroxine (100 pg per day) and clomiphene therapy (750 mg. per cycle), the patient conceived after the third clomiphene course and delivered at term in April, 1973. She delivered again in November, 1974.
Infertility following wedge resection
93
Case 3. D. Y., 39 years of age, had been married 19 years when first seen. She had been amenorrheic since the age of 16, after 1 year of almost regular menstruations, and was never pregnant. She was investigated and treated in several hospitals up to the age of 33, when wedge resection of the ovaries was performed in 1965. After operation she remained amenorrheic, but under HMG (Pergonal) therapy she menstruated and apparently had ovulatory cycles. No pregnancy, however, followed. On examination, we found a normally developed woman, without acne or hirsutism. Excretion of 17-ketosteroids was in the upper range (11 to 14 mg. per 24 hours), with a high excretion of dehydroepiandrosterone (1.6 mg. per 24 hours). Excretion of estrogens was very low (6.4 pg per 24 hours). Repeated LH plasma estimations gave values of 20 to 22 mU per milliliter. Dexamethasone suppression, followed by ovarian stimulation according to Jayle,4 seemed to establish heightened adrenal androgenic function. At laparoscopy, the right ovary appeared as a thick fibrotic band with the tip of the appendix attached. The left ovary was small and atrophic, adherent to the uterus. Uterus and tubes were normal. As ovarian resection had resulted in a condition very close to surgical castration, the patient was advised that further treatment was futile. Case 4. S. H., 26 years of age, had been married 8 years when she consulted us because of primary sterility. Since menarche at the age of 15, she had suffered from oligomenorrhea, with periods of 6 days’ duration every 2 to 3 months. In 1965, at the age of 19, shortly after marriage, she was submitted to bilateral ovarian resection. The menses became more regular, lasting 3 to 5 days every 29 to 35 days, but conception did not occur. Under clomiphene treatment she had apparently ovulatory cycles. Three years previously, hysterosalpingography demonstrated normal tubal patency. On examination we found a normally developed woman, with abundant acne, no hirsutism. The BBT curve was biphasic, with a short luteal phase. Endocrine work-up did not reveal any abnormality. 17Ketosteroid excretion and fractionation findings were well within normal limits. Serial daily LH plasma estimations showed values of 23 to 25 mu. per milliliter and a peak of 84 mu. per milliliter. Early luteal laparoscopy demonstrated a normal uterus, a right ovary covered by adhesions joining the sygmoid to the broad ligament. The distal part of both tubes was covered with adhesions. Tubal patency was preserved. No signs of ovulation were seen. The patient was operated on again in January, 1973. The dense peritoneal adhesions were carefully dissected and ovaries and tubes freed. A remarkable finding was that the adhesions on both ovaries converged to a linear scar, the suture line of the wedge resection.
94
Toaff,
Table
I
Toaff,
,Januan I, 1936 Am. J. cx5tet.‘(~\rlrcoi.
and Peyser
I. Pre- and postoperative
.Syi$
1. A.B.
1 Pre’fqeing
27
I
menstrual
.4ge at uledge resection 25
pattern,
and relevant
Preoperative
postoperative
symptoms
Oligomenorrhea 6 yr. dur. Sec. sterility. No hirsutism, no acne
I
findings
Postoperative course
Fever. abdominal
in seven infertile
Postoperative
women
menstrual
Oligomenorrhea.
junction
anovulation
pains 2. S. M.
28
19
Oligomenorrhea no acne
3. D.Y.
39
33
4. S. H.
26
19
5. M.E.
28
25
Normal
Regular 3 yr, then oligomenorrhea
Sec. amenorrhea of 17 yr. dur. Primary sterility. No hirsutism
Normal
Amenorrhea. Normal cycles under Pergonal treatment
Oligomenorrhea of 4 yr. dur. No conception during 1 yr. Acne, no hirsutism Oligomenorrhea 5 yr., then amenorrhea, 7 yr. Primary
Normal
Almost regular. but
sterility.
9 yr. No hirsutism,
anovulatory Normal
Amenorrhea. Satisfactory reaction to induction of ovulation
No hirsutism
cycles
with
clomiphene
6. A. 2.
27
24
Regular periods, anovulation. Primary sterility. No hirsutism
Normal
or Pergonal Regular, ovulatory cycles
7. W.S.
28
“1
Oligomenorrhea of 8 yr. dur. Primary sterility. Hirsutism, marked acne
Normal
Regular for a few months. then oligomenorrhea
Following operation, the woman was treated for several months with clomiphene (750 mg. per cycle). The cycles were apparently normal but the luteal phase remained short. A trial with prednisone (5 mg. per day) was successful and the patient conceived in the second month of prednisone therapy. She was delivered at term by cesarean section in May, 1974. Case 5. M. E., 28 years of age, was first seen after 8 years of marriage. Following menarche at the age of 13 and up to the age of 18 she had menstrual periods of 8 to 12 days’ duration every 2 to 4 months, then she became amenorrheic. Before and after marriage she was treated with prednisone. later with clomiphene, and then with HMG (Pergonal). Under clomiphene or Pergonal therapy she had apparently normal cycles but did not conceive. Conservative treatment was then abandoned and wedge resection performed at the age of 25, in 1970. As the menstrual rhythm remained unchanged, the patient was treated again with clomiphene and HCG and her periods became more regular. On admission, 3 years later, no physical abnormality was observed. Endocrine work-up was uncontributory. Following clomiphene, the patient had a normal menstruation, with typical BBT curve and elevated urinary excretion of pregnanediol. LH plasma estimations in consecutive days were 23, 25, 26, 48, and 72 mu. per milliliter, and FSH plasma estimations in the same days were 91: 84, 93, and 130 mu. per milliliter. At laparoscopy the ovaries were found to be almost
completely covered by thick adhesions involving both tubes and intestine loops. The patient has been advised that reconstructive surgery is mandatory in her present condition, but up to now has refused operation. Case 6. A. Z., 27 years of age, married 9 years, consulted us for primary sterility. Since the age of 13 she had regular periods of 4 days, every 28 days. After 1 year of marriage without conception, she sought medical advice and was treated with clomiphene for long periods. In 1970, at the age of 24, shortly after a laparoscopic examination, she was submitted to ovarian resection. Following operation her periods remained regular but the desired pregnancy was nof achieved. When examined, she had a biphasic BBT curve. normal LH plasma values with an ovulatory peak of 8 1 mu. per milliliter. At laparoscopy, a very small. micropolycystic, nonfunctioning ovary and a normal tube were seen on the right side. On the left, a normal ovary with a hemorrhagic corpus luteum was joined by adhesions to a patent tube, the fimbrial parr of which was included in transparent membranes. The pouch of Douglas was obliterated by adhesions. Reconstructive surgery has been advised. Case 7. W. S., 28 years of age, had been married 10 years when first seen because of primary sterility. Since the age of 13 she had scanty menstrual periods every 2 to 4 months. In 1968, at the age of 2 1, she had been submitted to wedge resection of the ovaries. Her periods became regular and remained so for several
Volume Number
submitted
Infertility following wedge resection
124 I
to wedge
resection
95
of ovaries Treatment
Laparoscopic
Endocrine assessment
findings
Peritoneal adhesions, severe. Atrophy of left ovary. R. polycystic ovary. R. periovarian and peritubal adhesions Severe peritubal and periovarian adhesions. Enlarged polycystic ovaries Atrophy of R. ovary. Ovarian appendicular adhesion. Small L. ovary adherent to post. leaf of broad ligament. Normal tubes Severe periovarian and peritubal adhesions. Tubes patent
Within
normal
Surgical limits
Hypothyroidism
Increased function, adrenal Within
androgenic probably origin
normal
Clomiphene
Conception and normal delivery
Removal of periovarian and peritubal adhesions. Terminal tuboplasty -
L-Thyroxine
Conception and normal delivery Patient dismissed
Lysis of periovarian and peritubal adhesions
Prednisone
Within normal limits. LH peak after clomiphene
Proposed,
R. atrophic ovary. L. ovary normal with hemorrhagic corpus luteum. Left peritubal adhesions Bilateral severe peritubal and periovarian adhesions
Normal
Proposed
androgenic probably origin
-
of
limits
of
months, then oligohypomenorrhea recurred. Since puberty she had suffered from acne, especially on the face. Physical examination revealed a fat woman with feminine habitus, normally developed breasts without galactorrhea, marked hirsutism on the face, lips, neck, and buttocks, and a male-type pubic escutcheon. Her external genitalia were normal, the uterus was of normal size, and the ovaries did not appear enlarged. The relevant endocrinologic findings were uppernormal values of 17-ketosteroid excretion ( 10.8 to 15.2 mg. per 24 hours) with high levels of androsterone (5.6 to 6.1 mg. per 24 hours) and dehydroepiandrosterone (1.8 to 3.0 mg. per 24 hours) on fractionation. Those high levels were reduced to within the normal range (1.9 and 0.8 mg. per 24 hours, respectively) under dexamethasone suppression, and remained normal under HCG stimulation. The total estrogen excretion was 7 to 15.7 pg per 24 hours. LH plasma estimations gave values of 14 to 16 mu. per milliliter. At laparoscopy, the left adnexae were found to be buried in a mass of thick adhesions. Peritubal and periovarian adhesions were present in lesser measure on the right side, where the ovary was polycystic, partially covered by the adherent ampullar part of the patent tube. The patient was classfied as having a mild case of adrenal androgenic hyperactivity. In December, 1973, she was submitted to reconstructive pelvic surgery. Under maintenance dexamethasone therapy she has
Results
Removal of periovarian and peritubal adhesions
Ovaries covered by thick adhesions involving tubes and intestine
Increased function, adrenal
Medical
patient
reluctant
Lysis of periovarian and peritubal adhesions, (Dec. 1973)
regular, currently
-
Conception and normal delivery -
-
-
Dexasone
Apparently ovulatory cycles
apparently ovulatory cycles. Her husband under treatment for oligospermia.
is
Comment Relevant data on the seven cases of unsuccesful ovarian resection described here are presented in Table I. A retrospective evaluation of the conditions which at different times and in different places prompted the abandonment of conservative therapy and the report to surgery is obviously preposterous and will not be pursued. Even in Case 2, where hypothyroidism was proved 9 years after surgery, the assumption that thyroid dysfunction caused the polycystic ovarian disease seems unjustified, as the patient had regular menses for 3 years following operation. It may be relevant, however, to note that, with the exception of Case 7, none of those patients had hirsutism, a prominent sign in the Stein-Leventhal syndrome. The common features in the present series are extensive periovarian and peritubal adhesions. A stormy postoperative course easily explains their presence in Case 1. All other cases were asymptomatic. Similar cases have been reported occasionally in the literature. Stein5 when reoperating six women for suspected recurrence of the polycystic ovarian disease, found dense peri-ovarian adhesions to omentum and/or bowel in four of them. Kistner6 was impressed
96 Toaff, Toaff, and Peyser
with the number of patients having recurrent amenorrhea or ohgoovulation subsequent to wedge resection in whom extensive peritubal adhesions were demonstrated by culdoscopy. Cohen’ studied a number of women who had relatively regular, apparently ovulatory cycles after ovarian resection, but remained infertile, and found endoscopic evidence of ovarian adhesions extensive enough to prevent ovulation. Goldzieher’ assumed that surgical factors may partly explain why fertility is corrected by wedge resection less often than the menstrual rhythm. The increasing use of gynecologic endoscopy, and particularly of laparoscopy, is now proving the important role of pelvic peritoneal adhesions in limiting the success of wedge resection.7 The present series of cases shows that the surgical procedure alone may be responsible for the persistence of infertility through a mechanical factor which makes pregnancy virtually impossible. Adequate reconstructive surgery becomes a precondition to successful fertilization in those cases where ovarian resection cured anovulation, and to successful fertilization fol-
Januar> Am. J. Obstet.
I, 19i(i Gynecol.
lowing induction of ovulation by clomiphene or other agents in those cases where ovarian surgery failed to correct anovulation. This policy has been applied in four of the six cases where reconstructive surgery was possible, with gratifying results. While it is impossible to establish at present the frequency of periovarian and peritubal adhesions following ovarian resection. it may be safely assumed that they constitute one of the important causes of failure of the surgical procedure to achieve its ends. Laparoscopy is therefore mandatory in the investigation of the unsuccesful results of bilateral ovarian resection. The observation of reversible or irreversible damage wrought by the surgical procedure indirectly supports the plea of Kistner* to relegate the surgical approach to a minor position in patients with SteinLeventhal syndrome. It stresses the importance of meticulous technique in the performance of conservative ovarian surgery during the reproductive age. Patients with pelvic adhesions, impairing ovarian and tubal function, should be offered the benefit of reconstructive surgery.
REFERENCES
1. Goldzieher, J. W.: In Marcus, S. L., and Marcus, C. G., editors: Advances in Obstetrics and Gynecology, Baltimore, 1967, The Williams & Wilkins Company, Vol. I, p. 354. 2. Goldzieher, J. W., and Green, J. A.: J. Clin. Endocrinol. Metab. 22: 325, 1962. 3. Jeffcoate, T. N. A.: AM. J. OBSTET. GYNECOL. 88: 143, 1964. 4. Jayle, M.: In Phillip, E., Barnes, J,, and Newhon, M., editors: Scientific Foundation of Obstetrics and Gynecology, London, 1970, William Heineman Medical Books, p. 549.
Fourth Annual Condmncs on Per&W
5. Stein, I. F.: In Greenblatt, R. B. editor., “Ovulation” Lippincot Co. 1966, pp. I50 - 157. 6. Kistner, R. W., in: Behrman, S. J., and Kistner, R. W., editors: Progress in Infertility. Boston, 1968, Little, Brown & Company, p. 407. 7. Cohen, M. R.: Laparoscopy, Culdoscopy and Gynecography; Technique and Atlas, Philadelphia, 1970, W. B. Saunders Company, p. 97. 8. Kistner, R. W.: In Gynecology, Principles and Practice, ed. 2, Chicago, 1971, Year Book Medical Publishers, Inc., p. 425.
AlleeMcim
The Fourth Annual Conference on Perinatal Medicine will be held March 25 and 26, 1976, at Callaway Gardens, Pine Mountain, Georgia. For further information, please contact: Micki L. Souma, M.D., and Louis Levy, M.D., Perinatology Department, The Medical Center, Columbus, Georgia 31901.
following
wedge resection of the ovaries
R. TOAFF M. E. TOAFF M. R. PEYSER Tel-Aviv,
Israel
Seven cases of polycystic ovarian disuse were investigated by !aparoscopr and rndocrinologic tests after failure of ovarian resech.@nto restore fertility. One case of bilateral and two cases of unilateral ovarian atrophy were recorded. In all seven patients the common features were extensive periovarian and pitubal adhesions. Four of the six patients amenable to cure were submitted to reconstructive surgery; three of them conceived and had normal deliveries. The present observations suppOrt the pka to relegate tk surgical approach to a minor position in patients with Stein-Leventhal syndrome and stress the importance of meticulous surgicak technique in the performance of ovarian surgery. Laparoscopic investigation is mandatory in all cases of unsuccessful ovarian resection.
DESPITE the growing interest in conservative methods for induction of ovulation in polycystic ovarian disease, wedge resection of the ovaries is still very much in use. Its beneficial effects are well documented. According to Goldzieher’s’ survey of published results, regular cycles follow surgery in 80 per cent of patients and desired pregnancy is achieved in 63 per cent. In some series, however, less than 10 per cent of subjects experienced regulation of menses and only 13 per cent conceived.2 It is generally agreed that fertility is restored less often than the menstrual rhythm.‘, 3 Questionable diagnosis and surgical complications may be involved in the failure of ovarian wedge resection to achieve its aim. The present report describes a series of seven cases of polycystic ovarian disease submitted to laparoscopic and endocrinologic investigations after the failure of surgery to restore fertility.
Stein-Leventhal syndrome, were investigated. Their complaint was persistent sterility, with or without obvious menstrual disorders. Four of them, whose operation records showed that at operation other pathology, such as malformations, tumors, or sequelae of pelvic inflammatory disease, was found beside polycystic ovaries, were not included in the present series in spite of similar findings. Six of the seven patients of the series were 26 to 28 years of age and one was 39. Ovarian surgery had been performed 2 to 9 years previously. All the patients had been treated, after endocrine studies were carried out before and after surgery, in different institutions and by private practitioners. As reliable data were not available in most cases, however, only information known to the patient and surgical records were used in establishing the early history. The investigations performed included the following. (1) Endocrine evaluation, including 17-ketosteroid excretion and their fractionation, adrenocortical suppression and ovarian stimulation (dexamethasoneHCG test according to Jayle*) plasma LH studies under basic conditions and after clomiphene administration, estrogen excretion, evaluation of thyroid function. (2) Hysterosalpingography with water-soluble contrast medium. (3) Laparoscopy, generally within 2 to 4 days after occurrence of the thermal shift in clomiphenetreated cycles.
Material and methods During a 6 year period (1967-1972) 11 women, who had previously been submitted to wedge resection of the ovaries in other hospitals with diagnosis of From the Department of Obstetrics and Gynecology ‘;4,” Hakilyah Matmnity Hospitnl, Municipal-Governmental Medical Center, Tel-Aviv University School of Medicine. Received
for publication
Revtied January Accepted Januq
September
24, 1974.
16, 1975. 16, 1975.
Reprint requests: R. Toaff, Tel-Aviv, Israel
M.D.,
Case 1. A. B., 27 years of age, sought secondary sterility and oligomenorrhea.
P. 0. Box 7079,
92
advice for Following
Volume Number
124 1
menarche at 13, she had normal periods for 3 days’ duration every 30 days up to the age of 21. Married at 17, she had at 19 a normal pregnancy and delivery. For the last 6 years she menstruated for 10 days every 45 to 60 days and she could not conceive. In 1965, at the age of 25, following culdoscopic examination which revealed enlarged, white, smooth ovaries, she was submitted to bilateral ovarian resection. The postoperative course was complicated by fever and abdominal pains. The menstrual rhythm remained unchanged and no conception followed. On examination, no physical abnormalities were observed. The endocrine findings were within normal limits. At laparoscopy, abundant pelvic peritoneal adhesions were found. The left adnexae were included in a single fibrotic mass. The right ovary was slightly enlarged, micropolycystic, and partially covered by the adherent, distorted tube. The patient was operated on again in 1967. The left ovary was reduced to a fibrotic band. The right ovary was freed from its extensive adhesions to the tube, the posterior wall of the uterus, and broad ligament. The peritoneal lining of the right tube was carefully reconstructed. The postoperative course was uneventful. One year later the patient conceived under clomiphene treatment (500 mg. per cycle, five cycles) and had a normal term delivery. Case 2. S. M., 28 years of age, had been married 8 years when first seen. Since menarche at the age of 10, she had menstruated 4 to 5 days every 1 to 4 months. For that reason she had been submitted to bilateral ovarian resection at the age of 19, shortly before marriage, in 1962. After operation she had normal menses for 3 years, followed by recurrence of oligomenorrhea. She was never pregnant. On physical examination, no endocrine stigmas were recorded. The only positive finding at endocrine evaluation was hypothyroidism. Her LH plasma values were 20 to 24 mU per milliliter. Under thyroxine treatment (100 Fg per day) her periods became regular, but were apparently anovulatory. At laparoscopy, a few months later, dense peritubal and periovarian adhesions were seen. The patient underwent reconstructive surgery in December, 1971. Both ovaries were enlarged and polycystic, almost completely covered by adhesions involving omentum and tubes. The distal part of the left tube was completely buried by adhesions deep into the pelvis. The left tube was only partially covered by adhesions, but the fimbriae were almost completely adherent to the ovarian surface. Following careful reconstruction and endocrine treatment which included thyroxine (100 pg per day) and clomiphene therapy (750 mg. per cycle), the patient conceived after the third clomiphene course and delivered at term in April, 1973. She delivered again in November, 1974.
Infertility following wedge resection
93
Case 3. D. Y., 39 years of age, had been married 19 years when first seen. She had been amenorrheic since the age of 16, after 1 year of almost regular menstruations, and was never pregnant. She was investigated and treated in several hospitals up to the age of 33, when wedge resection of the ovaries was performed in 1965. After operation she remained amenorrheic, but under HMG (Pergonal) therapy she menstruated and apparently had ovulatory cycles. No pregnancy, however, followed. On examination, we found a normally developed woman, without acne or hirsutism. Excretion of 17-ketosteroids was in the upper range (11 to 14 mg. per 24 hours), with a high excretion of dehydroepiandrosterone (1.6 mg. per 24 hours). Excretion of estrogens was very low (6.4 pg per 24 hours). Repeated LH plasma estimations gave values of 20 to 22 mU per milliliter. Dexamethasone suppression, followed by ovarian stimulation according to Jayle,4 seemed to establish heightened adrenal androgenic function. At laparoscopy, the right ovary appeared as a thick fibrotic band with the tip of the appendix attached. The left ovary was small and atrophic, adherent to the uterus. Uterus and tubes were normal. As ovarian resection had resulted in a condition very close to surgical castration, the patient was advised that further treatment was futile. Case 4. S. H., 26 years of age, had been married 8 years when she consulted us because of primary sterility. Since menarche at the age of 15, she had suffered from oligomenorrhea, with periods of 6 days’ duration every 2 to 3 months. In 1965, at the age of 19, shortly after marriage, she was submitted to bilateral ovarian resection. The menses became more regular, lasting 3 to 5 days every 29 to 35 days, but conception did not occur. Under clomiphene treatment she had apparently ovulatory cycles. Three years previously, hysterosalpingography demonstrated normal tubal patency. On examination we found a normally developed woman, with abundant acne, no hirsutism. The BBT curve was biphasic, with a short luteal phase. Endocrine work-up did not reveal any abnormality. 17Ketosteroid excretion and fractionation findings were well within normal limits. Serial daily LH plasma estimations showed values of 23 to 25 mu. per milliliter and a peak of 84 mu. per milliliter. Early luteal laparoscopy demonstrated a normal uterus, a right ovary covered by adhesions joining the sygmoid to the broad ligament. The distal part of both tubes was covered with adhesions. Tubal patency was preserved. No signs of ovulation were seen. The patient was operated on again in January, 1973. The dense peritoneal adhesions were carefully dissected and ovaries and tubes freed. A remarkable finding was that the adhesions on both ovaries converged to a linear scar, the suture line of the wedge resection.
94
Toaff,
Table
I
Toaff,
,Januan I, 1936 Am. J. cx5tet.‘(~\rlrcoi.
and Peyser
I. Pre- and postoperative
.Syi$
1. A.B.
1 Pre’fqeing
27
I
menstrual
.4ge at uledge resection 25
pattern,
and relevant
Preoperative
postoperative
symptoms
Oligomenorrhea 6 yr. dur. Sec. sterility. No hirsutism, no acne
I
findings
Postoperative course
Fever. abdominal
in seven infertile
Postoperative
women
menstrual
Oligomenorrhea.
junction
anovulation
pains 2. S. M.
28
19
Oligomenorrhea no acne
3. D.Y.
39
33
4. S. H.
26
19
5. M.E.
28
25
Normal
Regular 3 yr, then oligomenorrhea
Sec. amenorrhea of 17 yr. dur. Primary sterility. No hirsutism
Normal
Amenorrhea. Normal cycles under Pergonal treatment
Oligomenorrhea of 4 yr. dur. No conception during 1 yr. Acne, no hirsutism Oligomenorrhea 5 yr., then amenorrhea, 7 yr. Primary
Normal
Almost regular. but
sterility.
9 yr. No hirsutism,
anovulatory Normal
Amenorrhea. Satisfactory reaction to induction of ovulation
No hirsutism
cycles
with
clomiphene
6. A. 2.
27
24
Regular periods, anovulation. Primary sterility. No hirsutism
Normal
or Pergonal Regular, ovulatory cycles
7. W.S.
28
“1
Oligomenorrhea of 8 yr. dur. Primary sterility. Hirsutism, marked acne
Normal
Regular for a few months. then oligomenorrhea
Following operation, the woman was treated for several months with clomiphene (750 mg. per cycle). The cycles were apparently normal but the luteal phase remained short. A trial with prednisone (5 mg. per day) was successful and the patient conceived in the second month of prednisone therapy. She was delivered at term by cesarean section in May, 1974. Case 5. M. E., 28 years of age, was first seen after 8 years of marriage. Following menarche at the age of 13 and up to the age of 18 she had menstrual periods of 8 to 12 days’ duration every 2 to 4 months, then she became amenorrheic. Before and after marriage she was treated with prednisone. later with clomiphene, and then with HMG (Pergonal). Under clomiphene or Pergonal therapy she had apparently normal cycles but did not conceive. Conservative treatment was then abandoned and wedge resection performed at the age of 25, in 1970. As the menstrual rhythm remained unchanged, the patient was treated again with clomiphene and HCG and her periods became more regular. On admission, 3 years later, no physical abnormality was observed. Endocrine work-up was uncontributory. Following clomiphene, the patient had a normal menstruation, with typical BBT curve and elevated urinary excretion of pregnanediol. LH plasma estimations in consecutive days were 23, 25, 26, 48, and 72 mu. per milliliter, and FSH plasma estimations in the same days were 91: 84, 93, and 130 mu. per milliliter. At laparoscopy the ovaries were found to be almost
completely covered by thick adhesions involving both tubes and intestine loops. The patient has been advised that reconstructive surgery is mandatory in her present condition, but up to now has refused operation. Case 6. A. Z., 27 years of age, married 9 years, consulted us for primary sterility. Since the age of 13 she had regular periods of 4 days, every 28 days. After 1 year of marriage without conception, she sought medical advice and was treated with clomiphene for long periods. In 1970, at the age of 24, shortly after a laparoscopic examination, she was submitted to ovarian resection. Following operation her periods remained regular but the desired pregnancy was nof achieved. When examined, she had a biphasic BBT curve. normal LH plasma values with an ovulatory peak of 8 1 mu. per milliliter. At laparoscopy, a very small. micropolycystic, nonfunctioning ovary and a normal tube were seen on the right side. On the left, a normal ovary with a hemorrhagic corpus luteum was joined by adhesions to a patent tube, the fimbrial parr of which was included in transparent membranes. The pouch of Douglas was obliterated by adhesions. Reconstructive surgery has been advised. Case 7. W. S., 28 years of age, had been married 10 years when first seen because of primary sterility. Since the age of 13 she had scanty menstrual periods every 2 to 4 months. In 1968, at the age of 2 1, she had been submitted to wedge resection of the ovaries. Her periods became regular and remained so for several
Volume Number
submitted
Infertility following wedge resection
124 I
to wedge
resection
95
of ovaries Treatment
Laparoscopic
Endocrine assessment
findings
Peritoneal adhesions, severe. Atrophy of left ovary. R. polycystic ovary. R. periovarian and peritubal adhesions Severe peritubal and periovarian adhesions. Enlarged polycystic ovaries Atrophy of R. ovary. Ovarian appendicular adhesion. Small L. ovary adherent to post. leaf of broad ligament. Normal tubes Severe periovarian and peritubal adhesions. Tubes patent
Within
normal
Surgical limits
Hypothyroidism
Increased function, adrenal Within
androgenic probably origin
normal
Clomiphene
Conception and normal delivery
Removal of periovarian and peritubal adhesions. Terminal tuboplasty -
L-Thyroxine
Conception and normal delivery Patient dismissed
Lysis of periovarian and peritubal adhesions
Prednisone
Within normal limits. LH peak after clomiphene
Proposed,
R. atrophic ovary. L. ovary normal with hemorrhagic corpus luteum. Left peritubal adhesions Bilateral severe peritubal and periovarian adhesions
Normal
Proposed
androgenic probably origin
-
of
limits
of
months, then oligohypomenorrhea recurred. Since puberty she had suffered from acne, especially on the face. Physical examination revealed a fat woman with feminine habitus, normally developed breasts without galactorrhea, marked hirsutism on the face, lips, neck, and buttocks, and a male-type pubic escutcheon. Her external genitalia were normal, the uterus was of normal size, and the ovaries did not appear enlarged. The relevant endocrinologic findings were uppernormal values of 17-ketosteroid excretion ( 10.8 to 15.2 mg. per 24 hours) with high levels of androsterone (5.6 to 6.1 mg. per 24 hours) and dehydroepiandrosterone (1.8 to 3.0 mg. per 24 hours) on fractionation. Those high levels were reduced to within the normal range (1.9 and 0.8 mg. per 24 hours, respectively) under dexamethasone suppression, and remained normal under HCG stimulation. The total estrogen excretion was 7 to 15.7 pg per 24 hours. LH plasma estimations gave values of 14 to 16 mu. per milliliter. At laparoscopy, the left adnexae were found to be buried in a mass of thick adhesions. Peritubal and periovarian adhesions were present in lesser measure on the right side, where the ovary was polycystic, partially covered by the adherent ampullar part of the patent tube. The patient was classfied as having a mild case of adrenal androgenic hyperactivity. In December, 1973, she was submitted to reconstructive pelvic surgery. Under maintenance dexamethasone therapy she has
Results
Removal of periovarian and peritubal adhesions
Ovaries covered by thick adhesions involving tubes and intestine
Increased function, adrenal
Medical
patient
reluctant
Lysis of periovarian and peritubal adhesions, (Dec. 1973)
regular, currently
-
Conception and normal delivery -
-
-
Dexasone
Apparently ovulatory cycles
apparently ovulatory cycles. Her husband under treatment for oligospermia.
is
Comment Relevant data on the seven cases of unsuccesful ovarian resection described here are presented in Table I. A retrospective evaluation of the conditions which at different times and in different places prompted the abandonment of conservative therapy and the report to surgery is obviously preposterous and will not be pursued. Even in Case 2, where hypothyroidism was proved 9 years after surgery, the assumption that thyroid dysfunction caused the polycystic ovarian disease seems unjustified, as the patient had regular menses for 3 years following operation. It may be relevant, however, to note that, with the exception of Case 7, none of those patients had hirsutism, a prominent sign in the Stein-Leventhal syndrome. The common features in the present series are extensive periovarian and peritubal adhesions. A stormy postoperative course easily explains their presence in Case 1. All other cases were asymptomatic. Similar cases have been reported occasionally in the literature. Stein5 when reoperating six women for suspected recurrence of the polycystic ovarian disease, found dense peri-ovarian adhesions to omentum and/or bowel in four of them. Kistner6 was impressed
96 Toaff, Toaff, and Peyser
with the number of patients having recurrent amenorrhea or ohgoovulation subsequent to wedge resection in whom extensive peritubal adhesions were demonstrated by culdoscopy. Cohen’ studied a number of women who had relatively regular, apparently ovulatory cycles after ovarian resection, but remained infertile, and found endoscopic evidence of ovarian adhesions extensive enough to prevent ovulation. Goldzieher’ assumed that surgical factors may partly explain why fertility is corrected by wedge resection less often than the menstrual rhythm. The increasing use of gynecologic endoscopy, and particularly of laparoscopy, is now proving the important role of pelvic peritoneal adhesions in limiting the success of wedge resection.7 The present series of cases shows that the surgical procedure alone may be responsible for the persistence of infertility through a mechanical factor which makes pregnancy virtually impossible. Adequate reconstructive surgery becomes a precondition to successful fertilization in those cases where ovarian resection cured anovulation, and to successful fertilization fol-
Januar> Am. J. Obstet.
I, 19i(i Gynecol.
lowing induction of ovulation by clomiphene or other agents in those cases where ovarian surgery failed to correct anovulation. This policy has been applied in four of the six cases where reconstructive surgery was possible, with gratifying results. While it is impossible to establish at present the frequency of periovarian and peritubal adhesions following ovarian resection. it may be safely assumed that they constitute one of the important causes of failure of the surgical procedure to achieve its ends. Laparoscopy is therefore mandatory in the investigation of the unsuccesful results of bilateral ovarian resection. The observation of reversible or irreversible damage wrought by the surgical procedure indirectly supports the plea of Kistner* to relegate the surgical approach to a minor position in patients with SteinLeventhal syndrome. It stresses the importance of meticulous technique in the performance of conservative ovarian surgery during the reproductive age. Patients with pelvic adhesions, impairing ovarian and tubal function, should be offered the benefit of reconstructive surgery.
REFERENCES
1. Goldzieher, J. W.: In Marcus, S. L., and Marcus, C. G., editors: Advances in Obstetrics and Gynecology, Baltimore, 1967, The Williams & Wilkins Company, Vol. I, p. 354. 2. Goldzieher, J. W., and Green, J. A.: J. Clin. Endocrinol. Metab. 22: 325, 1962. 3. Jeffcoate, T. N. A.: AM. J. OBSTET. GYNECOL. 88: 143, 1964. 4. Jayle, M.: In Phillip, E., Barnes, J,, and Newhon, M., editors: Scientific Foundation of Obstetrics and Gynecology, London, 1970, William Heineman Medical Books, p. 549.
Fourth Annual Condmncs on Per&W
5. Stein, I. F.: In Greenblatt, R. B. editor., “Ovulation” Lippincot Co. 1966, pp. I50 - 157. 6. Kistner, R. W., in: Behrman, S. J., and Kistner, R. W., editors: Progress in Infertility. Boston, 1968, Little, Brown & Company, p. 407. 7. Cohen, M. R.: Laparoscopy, Culdoscopy and Gynecography; Technique and Atlas, Philadelphia, 1970, W. B. Saunders Company, p. 97. 8. Kistner, R. W.: In Gynecology, Principles and Practice, ed. 2, Chicago, 1971, Year Book Medical Publishers, Inc., p. 425.
AlleeMcim
The Fourth Annual Conference on Perinatal Medicine will be held March 25 and 26, 1976, at Callaway Gardens, Pine Mountain, Georgia. For further information, please contact: Micki L. Souma, M.D., and Louis Levy, M.D., Perinatology Department, The Medical Center, Columbus, Georgia 31901.