Moderate Endometriosis Research Articles

Surgical treatment of endometriosis via laser laparoscopy

The carbon dioxide laser has been used laparoscopically for the removal of endometriotic implants, excision of endometrioma capsules, and lysis of adnexal adhesions in 102 patients. These patients were followed for a period ranging from 12 to 18 months, during which time there were 62 pregnancies, including 9 spontaneous abortions and 1 elective termination. The rates of conception after surgery were as follows: 75% for patients with mild endometriosis, 62% for patients with moderate endometriosis, 42.1% for patients with severe endometriosis, and 50% for patients with extensive endometriosis. Of 102 patients presenting with infertility attributed to endometriosis, 60.7% conceived within 24 months after laser laparoscopy. In this patient group, no immediate or subsequent laparotomy was required before conception was achieved, nor was hormonal therapy enacted during the study period after surgery.

Analysis of sequential treatment protocols for endometriosis-associated infertility

The evaluation of comparative pregnancy data in clinical studies is subject to a variety of biases. One such bias, when treated patients are retrospectively compared with untreated control subjects, results from the fact that treated patients must remain infertile from time of diagnosis to time of treatment while no such requirements is maintained for untreated control subjects. This bias is also apparent when patients undergo sequential treatments and transfer from one comparison group to another. We have eliminated this problem by applying the Mantel-Byar approach for constructing and comparing modified life tables that reflect sequential changes of treatment status. To illustrate this we applied commonly used methods of analysis as well as the Mantel-Byar method to infertile endometriosis patients attempting pregnancy. One hundred thirty consecutive patients were evaluated retrospectively, with 42 undergoing expectant management only, seven experiencing a conservative surgical procedure only, and 81 having a conservative surgical procedure after a variable period of expectant management. Use of Mantel-Byar analysis revealed no significant overall increase in pregnancy rate with conservative surgical procedures versus expectant management (χ2 = 0.225, df = 1). To further assess the potential value of conservative surgical procedures in fertility enhancement, the data were stratified by degree of endometriosis. The adjusted χ2 was 1.621. No significant difference was noted between the two therapeutic approaches with mild disease (n = 35, χ2 = 0.0175) or moderate endometriosis (n = 59, χ2 = 0.424). Conservative surgical procedures appear to be therapeutic, however, in women with severe disease (n = 36, χ2 = 5.12, p < 0.05). These results differed substantially from those obtained with the more biased analytic methods routinely used in clinical fertility trials. This study illustrates the utility of the Mantel-Byar approach as a valuable tool in the evaluation of response time data involving transient therapeutic states and one particularly adaptable to retrospective infertility studies involving sequential treatment approaches.

Association of endometriosis and spontaneous abortion: effect of control group selection.

Endometriosis has been associated with an increased incidence of spontaneous abortion, compared with the abortion rate of the general population. To assess whether a separate control group would affect these conclusions, we studied 139 consecutive infertility patients with laparoscopically proven endometriosis to determine the incidence of spontaneous abortion. Ninety-five of these patients underwent conservative surgical resection of endometriosis, and 44 patients opted for expectant management. There was no significant difference between these two groups in average age, duration of infertility, or proportion of patients with primary infertility. The average spontaneous abortion rate before diagnosis for all patients was 63.1%. After surgical treatment, the abortion rate dropped to 0% (P less than 0.000001) for all stages of disease. However, even in those patients who received expectant management only, the abortion rate fell to 16.7% and 21.4% for mild and moderate endometriosis, respectively (P less than 0.001). These results suggest that the spontaneous abortion rate in untreated endometriosis may not be as high as previously reported and may not be significantly different from the rate in the general population. The data also emphasize the need for well-defined control groups when assessing the effects of a treatment regimen.

A comparison of danazol and conservative surgery for the treatment of infertility due to mild or moderate endometriosis

Although both medical and surgical therapy have been widely used in the treatment of infertility due to endometriosis, there is little information on the comparative success of these treatment modalities. In a group of 313 infertile women who presented to The Johns Hopkins Hospital with mild or moderate endometriosis in whom there had been no previous therapy, the results of danazol (91 patients) and conservative surgery (133 patients) were compared. It was found that the cumulative pregnancy curves of the two groups virtually coincided. There was no significant difference in the estimated proportion of patients who were "cured," i.e., who would ultimately conceive if followed for a long enough period (68.3% for surgery versus 74.0% for danazol), nor in the monthly rate of pregnancy among those cured (5.7% versus 4.0%), respectively.

Serum estradiol and danazol. I. Endometriosis response, side effects, administration interval, concurrent spironolactone and dexamethasone

Serum estradiol (E 2 ) levels and resolution of endometriosis were evaluated in 42 women after 75 days of danazol treatment. Complete or almost complete remission occurred when radioimmunoassay E 2 levels were < 15 pg/ml in extensive, < 22 pg/ml in severe, and < 41 pg/ml in moderate endometriosis. E 2 ≤ 20 pg/ml occurred in 23% of 104 patients given 400 mg every 12 hours but in none weighing over 150 pounds (68 kg). E 2 > 100 pg/ml occurred in 7%. The mean E 2 levels were identical with 400 mg every 12 hours and 200 mg every 8 hours. The E 2 level was 40% lower with 200 mg every 6 hours than with 400 mg every 12 hours ( P < 0.001). Dexamethasone further decreased E 2 levels by 61% ( P < 0.001). Spironolactone decreased androgen symptoms but increased E 2 levels by 49% ( P < 0.01).

Combined laparoscopic surgery and danazol therapy for pelvic endometriosis

The role of combined laparoscopic surgery and postoperative danazol treatment for endometriosis in infertile patients has been reviewed in 66 cases. Thirty-five patients with mild endometriosis and twenty-five patients with moderate endometriosis received a standardized laparoscopic surgical procedure followed by danazol therapy with a minimum of 6 months’ follow-up. Six patients with severe endometriosis received 4 months of danazol treatment followed by conservative surgery. Fifty-four percent of these patients conceived, with 92% delivering a live child. By excluding patients with other significant infertility factors, a “corrected” fertility rate of 68% was obtained. The majority of patients conceiving after danazol treatment did so within the first 6 months after therapy. Reported complications to drug treatment were minimal. Second-look laparoscopy when performed in patients who had not conceived within 6 months revealed a significant decrease in residual endometriosis.

Serum estradiol and danazol. I. Endometriosis response, side effects, administration interval, concurrent spironolactone and dexamethasone

Serum estradiol (E2) levels and resolution of endometriosis were evaluated in 42 women after 75 days of danazol treatment. Complete or almost complete remission occurred when radioimmunoassay E2 levels were less than 15 pg/ml in extensive, less than 22 pg/ml in severe, and less than 41 pg/ml in moderate endometriosis. E2 less than or equal to 20 pg/ml occurred in 23% of 104 patients given 400 mg every 12 hours but in none weighing over 150 pounds (68 kg). E2 greater than 100 pg/ml occurred in 7%. The mean E2 levels were identical with 400 mg every 12 hours and 200 mg every 8 hours. The E2 level was 40% lower with 200 mg every 6 hours than with 400 mg every 12 hours (P less than 0.001). Dexamethasone further decreased E2 levels by 61% (P less than 0.001). Spironolactone decreased androgen symptoms but increased E2 levels by 49% (P less than 0.01).

Etiology of infertility in monkeys with endometriosis: luteinized unruptured follicles, luteal phase defects, pelvic adhesions, and spontaneous abortions

To elucidate the etiology of infertility due to endometriosis, we autografted endometrial or adipose tissue to the pelvic peritoneum of 21 cynomolgus monkeys. These primates were divided into five groups: control animals with adipose tissue autografts (n = 5), animals with microscopic endometriosis (n = 5), animals with mild endometriosis (n = 5), animals with moderate endometriosis (n = 4), and animals with severe endometriosis (n = 2). During three subsequent menstrual cycles, each animal underwent (1) serial assay of peripheral serum gonadotropins and steroids; (2) mating timed according to daily serum 17 beta-estradiol; and (3) laparotomy to document an ovulatory stigma. The chemical and term pregnancy rates were lower among monkeys with moderate or severe endometriosis, as compared with control animals. The impaired fertility in monkeys with endometriosis appeared to be mediated primarily by failure of follicular rupture and/or pelvic adhesions.

Pregnancy rates following various therapy modes for endometriosis in infertile patients.

A total of 215 infertile patients with endometriosis verified at least laparoscopically were treated between 1977 and 1982 by conservative surgery alone (N = 90), or with danazol, 600 mg daily and most often for 6 months, either alone (N = 59) or postoperatively (N = 44), or by laparoscopic electrocautery of endometriotic foci (N = 18). The mean age and duration of infertility were about the same in all groups. The disease was mild in the electrocoagulated group, moderate in the groups treated either exclusively surgically or with danazol, and most severe among the patients who received danazol following surgery. The uncorrected pregnancy rate after conservative surgery was 43% and the mean interval until conception was 11.7 months. After 6 months' danazol treatment the uncorrected pregnancy rate was 56% and the mean interval until conception was significantly (p less than 0.02) shorter, 6.7 months. Conservative surgery followed by danazol treatment for 6 months resulted in fewer pregnancies (pregnancy rate 32%) but the mean interval until conception was about the same (6.9 months) as after danazol therapy alone. After laparoscopic electrocautery the pregnancy rate was only 17%. In view of these results, we recommend that for infertile patients with mild or moderate endometriosis the recommended treatment should be medical, e.g., danazol 600 mg daily for 6 months.

A comparison of danazol and conservative surgery for the treatment of infertility due to mild or moderate endometriosis

Although both medical and surgical therapy have been widely used in the treatment of infertility due to endometriosis, there is little information on the comparative success of these treatment modalities. In a group of 313 infertile women who presented to The Johns Hopkins Hospital with mild or moderate endometriosis in whom there had been no previous therapy, the results of danazol (91 patients) and conservative surgery (133 patients) were compared. It was found that the cumulative pregnancy curves of the two groups virtually coincided. There was no significant difference in the estimated proportion of patients who were “cured,” i.e., who would ultimately conceive if followed for a long enough period (68.3% for surgery versus 74.0% for danazol), nor in the monthly rate of pregnancy among those cured (5.7% versus 4.0%), respectively.

Gonadotropin-releasing hormone agonist suppresses ovulation, menses, and endometriosis in monkeys: an individualized, intermittent regimen.

This study was designed to test the efficacy of a long-acting GnRH agonist (alpha) for inhibition of ovulation and menses in monkeys as well as suppression of mild to moderate endometriosis through an individualized, intermittent regimen. Endometriosis was surgically induced in 21 cynomolgus monkeys; ectopic tissue viability was verified histologically. GnRH alpha (leuprolide, D-Leu6-Pro9-Net-LHRH, Abbott Laboratories) was injected weekly in treatment cycle 1 (10 microgram/kg, sc; n = 15). Ovulation and menses ceased in 6 of 15 females. For the remaining 9 monkeys, the GnRH alpha dose was increased to 15 microgram/kg weekly in treatment cycle 2. Still, 4 monkeys resisted suppression; in treatment cycle 3, their regimen increased to 15 microgram/kg every fourth day. Thus, anovulation and amenorrhea was achieved in 14 of 15 monkeys within 90 days, seemingly as a result of ovarian desensitization, since GnRH alpha injections usually enhanced serum LH and FSH levels (P less than 0.05). Frequent laparotomies and daily hormonal profiles of estradiol, progesterone, FSH, and LH in serum confirmed these findings. After treatment, 12 of 15 monkeys manifested resolution of ectopic endometrial tissue; concurrently, there was no change in the severity of endometriosis in the 6 saline-injected controls. Six of 15 monkeys became pregnant within 90 days after cessation of GnRH alpha injections; 1 of 6 control females conceived. These findings may encourage consideration of clinical investigations employing individualized and/or intermittent GnRH alpha administration for the treatment of endometriosis or to achieve contraception.

Combined laparoscopic surgery and danazol therapy for pelvic endometriosis

The role of combined laparoscopic surgery and postoperative danazol treatment for endometriosis in infertile patients has been reviewed in 66 cases. Thirty-five patients with mild endometriosis and twenty-five patients with moderate endometriosis received a standardized laparoscopic surgical procedure followed by danazol therapy with a minimum of 6 months' follow-up. Six patients with severe endometriosis received 4 months of danazol treatment followed by conservative surgery. Fifty-four per cent of these patients conceived, with 92% delivering a live child. By excluding patients with other significant infertility factors, a "corrected" fertility rate of 68% was obtained. The majority of patients conceiving after danazol treatment did so within the first 6 months after therapy. Reported complications to drug treatment were minimal. Second-look laparoscopy when performed in patients who had not conceived within 6 months revealed a significant decrease in residual endometriosis.