Monday, September 28, :00 P.M. to 5:00 P.M. Session 4-Society of Reproductive Surgeons

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1 024 METALLOPROTEASE INHIBITOR ACTIVITY IN HUMAN OVARIAN FOLLICULAR FLUID. T. E. Curry, Jr., S. L. Sanders, N. G. Pedigo, R. S. Estes, E. A. Wilson, M. W. Vernon, Dept. of Ob/Gyn and Anatomv, Univ. of Kentucky, Lexington, KY. - The metalloprotease inhibitors, TIMP (tissue inhibitor of metalloproteases) and 0!2-macroglobulin, regulate the activity of the metalloproteases, collagenase, gelatinase and proteoglycanase. We have previously observed an increase in both collagenase and metalloprotease inhibitor activity associated with ovulation in the rat. In the present study, we measured metalloprotease inhibitor activity in follicular fluid from patients in our in vitro fertilization program. The relationship between inhibitor activity and sterqid content was examined and the inhibitor(s) were partially purified and characterized. Inhibitor activity was determined by an assay based on enzymatic degradation of a red azodye, Azocoll, by a uterine metalloprotease. Inhibition of the uterine metalloprotease activity by follicular fluid aliquots containing inhibitor was quantitated spectrophotometrically. A positive correlation was observed between inhibitory activity (N = 25) and both follicular estradiol (p < 0.001) and progesterone (p < 0.05) concentrations. Chromatography of the follicular fluid on Sepharose 6B resulted in two peaks of inhibitory activity. The peak of small molecular weight (MW) inhibitor shared many of the properties of TIMP (Biochem. J. 218:277, 1984). The inhibitor had an apparent MW = 26-29K, was stable to heat (60 oc) and methylamine (200 mm), and was destroyed by reduction and alkylation, a procedure reported to destroy inhibitors. The large MW inhibitor had the characteristics of 0!2-macroglobulin; a MW ::: 700K, was sensitive to heat, methylamine, and reduction and alkylation. Thus follicular fluid contains metalloprotease inhibitor activity which is steroid related and may be hormonally regulated. Ovarian metalloprotease inhibitors may regulate connective tissue remodeling during ovulation. Supported by BRSG #RR Monday, September 28, :00 P.M. to 5:00 P.M. Session 4-Society of Reproductive Surgeons 025 FEBRILE MORBIDITY AFTER HYSKON USE DURING ECTOPIC PREGNANCY SURGERY. K. Dorward, T. J. Mullin, Dept. of Ob/Gyn and Reprod. Sci., Univ. of California, San Francisco, CA. Hyskon (32% Dextran 70) has been found to be safe for use in infertility surgery as an adjuvant for reducing postoperative adhesions. Concern over enhancement of bacterial growth in the presence of active salpingitis has limited its use in surgery for ectopic pregnancy. The incidence of postoperative fever was studied in a consecutive series of 61 patients undergoing surgery for ectopic pregnancy at San Francisco General Hospital from January 1986 to February All patients had intraoperative cultures of tube/gestational site for aerobes, anaerobes and Chlamydia, as well as peritoneal lavage with at least two liters of Plasmalyte to clear blood from the abdomen prior to closure. Patients were randomized by hospital medical number to have either Hyskon (200cc) or Plasmalyte (200cc) instilled peritoneally at closure of the abdomen. Averages of age (27), gravidity (3) and parity (1) for both groups of patients were comparable. Historical infertility factors (prior G.C., PID, IUD use, ectopic pregnancy, pelvic surgery and failure to conceive after one or more years of unprotected coitus) were found in 18 of 31 (58%) Plasmalyte and in 18 of 30 (60%) Hyskon patients. Operative findings of pelvic adhesions or tubal damage were found in 13 of 31 (42%) Plasmalyte and 15 out of 30 (50%) receiving Hyskon patients. Chi-square analysis showed no difference between the groups for these two factors. All intraoperative cultures showed no significant growth. Postoperative febrile morbidity (T ~ 38.0 C) was documented in 9 out of 31 (29%) Plasmalyte patients, and 11 out of 30 (37%) Hyskon patients. Fever work-up included chest x-ray, cultures of blood, urine, sputum, cervix, endometrium, and culdocentesis fluid. Sources of fever were the following: atelectasis in 2 Plasmalyte and 4 Hyskon patients, pneumonia in 1 Plasmalyte and 1 Hyskon patient, urinary tract infection in 1 Plasmalyte and 1 Hykson patient, pelvic infection in 2 Plasmalyte patients and 1 Hyskon patient, abdominal wound seroma in 1 Plasmalyte and 2 Hyskon patients, and an unexplained source in 2 patients in each group. Chi-square analysis failed to show a statistically significant difference between the two groups for febrile morbidity or fever source. We conclude that Hyskon use in ectopic pregnancy does not increase postoperative febrile morbidity or apparent pelvic infection. Abstracts 11

2 ~ ~ 026 ISTHMIC ECTOPIC PREGNANCY AND SALPINGITIS ISTHMICA NODOSA. R. J. Homm, G. Holtz, Dept. of Ob/Gyn, Medical Univ. of South Carolina, Charleston, SC. We have been impressed with the association of isthmic ectopic pregnancy and salpingitis isthmica nodosa (SIN). A retrospective study of a six year period ( ) was therefore instituted to evaluate this. Two hundred eighty five charts of patients with a discharge diagnosis of ectopic pregnancy were reviewed. Excluded from further consideration were patients with previous tubal reparative surgery, linear salpingotomy, failed sterilization or ectopic pregnancy following embryo transfer. Of the remaining 255 cases, 39 (15.3%) were determined to be isthmic in location. The diagnosis of SIN was made on routine review ofthe resected tubal segment. There was no difference in t!'le apparent incidence of SIN whether managed by total salpingectomy or segmental resection. SIN was noted in 17 of 37 cases (45.9%) of isthmic ectopic pregnancy. Two cases in which linear salpingotomy was performed were not included in the calculation of the incidence. A prospective study may well have noted a higher frequency. This significant association of SIN with ectopic pregnancy, its known association with infertility and the frequent bilateralality of SIN has significant ramifications for management. Recommended conservative therapy of isthmic ectopic pregnancy is therefore segmental resection with postoperative emphasis on documentation of SIN. A postoperative hysterosalpingogram is recommended if there is a grossly abnormal contralateral tube or when SI N is noted in the pathological specimen. Even with patency, if findings suggestive of SIN are noted in the contralateral tube, consideration of resection with reanastomosis is appropriate to reduce the recurrence risk for ectopic pregnancy. 027 REDUCTION OF ADHESIONS USING TC 7 ADHESION BARRIER IN WOMEN UNDERGOING INFERTILITY SURGERY. S. M. Cohen', R. R. Franklin", G. W. Patton"', 'Univ. of Massachusetts Medical Center, Worcester, MA; "Baylor College of Medicine, Houston, TX; "'Southeastern Fertility Center, Charleston, SC. TC 7, a resorbable biocompatible adhesion barrier, has been shown to be efficacious in reducing adhesion formation in rabbit models. To assess efficacy in humans, fifteen patients undergoing reproductive pelvic surgery were enrolled in a multicenter study. All had bilateral pelvic sidewall adhesions. Excluded were patients with endometriosis. The use of instillates such as 32% Dextran 70 and corticosteroids were prohibited. Following adhesiolysis at laparotomy, TC 7 was randomly assigned to one sidewall in an amount sufficient to cover all raw sidewall surfaces; the untreated contralateral sidewall served as control. A second look laparoscopy for evaluation of pelvic adhesions was performed within fifteen weeks. Comparison was made of the raw surface sidewall area at laparotomy and laparoscopy using an improvement ratio of (Adhesion initial-adhesion final/adhesion initial) on the treated and untreated sidewalls. Sidewalls treated with TC 7 had a median ratio of 1.00 and ranged from.77 to 1.00, while untreated sidewalls had a median ratio of.45 and ranged from to 1.00, demonstrating a significant improvement on the TC 7 treated sidewalls ( p<0.05). No TC 7 was observed in any women at the time of laparoscopy. There were no complications noted in any patient. These preliminary results indicated that TC 7 Adhesion Barrier effectively reduced the extent and/or severity of post-surgical adhesions on the female pelvic sidewall. 12 Abstracts

3 028 PREVALENCE OF OVARIAN CANCER FOUND AT THE TIME OF INFERTILITY MICROSURGERY. C. W. Lais, T. J. Williams, Dept. of Ob/Gyn, Mayo Clinic and Mayo Foundation, Rochester, MN. The prevalence of ovarian carcinoma found at the time of infertility surgery has never been reported. We reviewed 841 female patients operated on for infertility and found 625 patients with a preoperative diagnosis of either tubal adhesive disease or endometriosis. The other 271 patients had tubal reversals and were excluded from these calculations. Of the 625 patients, 29 were found to have ovarian neoplasm, 23 benign and 6 malignant. The prevalence of ovarian carcinoma for women under 40 years of age is approximately 1 in 424. In this study, the prevalence was 1 in 95. Further, laparoscopy was performed preoperatively in 5 out of the 6 patients with ovarian carcinoma yet no patient was correctly diagnosed with this procedure. In summary, the prevalence of ovarian carcinoma is these premenopausal, infertile women was higher than expected, and laparoscopy failed to identify these patients. 029 ONE TO SIX YEAR FOLLOW-UP OF HYSTEROSCOPIC METROPLASTY. D. Daly, D. Maier, Dept. of Ob/Gyn, Univ. of Massachusetts Medical School, Worcester, MA, Dept. of Ob/Gyn, Univ. of Connecticut Medical School, Farmington, CT. Fifty-two patients (pts) who underwent hysteroscopic metroplasty for uterine septum from 8/81 to 12/85 were reviewed for subsequent gynecologic problems and obstetrical (08) outcome. Complete followup was obtained in 41 pts with no gynecologic problems reported. The 52 pts were divided into 3 groups based on 08 history (Hx). Preop and postop 08 outcomes were assessed. 1) Patients with 1 st trimester Abortion (Abs) 2) Patients with 2nd trimester Abs or Premie Pts Pregnancy 1st Abs 2nd Abs Premie Term Living Pts Pregnancy 1st Abs 2nd Abs Premie Term Living ) 3 pts lost to followup (LTF), 2 pts no preg. 5) 2 pts LTF, 2 no pregnancy 2) 1 pt Ab only, 19 pts term preg, 3 pts preg. 6) 2 sets twins (premie), 2 pts preg. 3) 1 complicated (fetal distress), 75% vag. del. 7) 2 complicated pregnancy, 1 labor 30 wks 4) 1 pt 22 week delivery-incompetent cervix 1 fetal distress at 37 wks-vsd (3) Thirteen pts with no previous pregnancies had metroplasties, of these only 3 of 7 pts receiving treatment for other infertility problems conceived post metroplasty. Hysteroscopic metroplasty, 1) is not associated with any subsequent gynecologic disorders, 2) is very effective in treating pts with septums and Hx of 1 st trimester Ab, 3) pts with 2nd trimester Abs or premie delivery are benefited by metroplasty but are still at risk for premature labor, 4) Hysteroscopic metroplasty does not "cure" unexplained infertility. It is concluded that hysteroscopic metroplasty is the treatment of choice in pts with uterine septums associated with pregnancy loss. Pts with a Hx of 2nd and 3rd trimester loss require close monitoring in subsequent pregnancies. Abstracts 13

4 030 CONSERVATIVE MANAGEMENT OF PLATEAUING HCG TITERS IN WOMEN WITH TUBAL DISEASE. S. Lindheim, G. Lavy, M. L. Polan, Dept. of Ob/Gyn, Yale University, New Haven, CT. The persistence of low levels of serum human chorionic gonadotropin (hcg) in women with known tubal disease, or following in vitro fertilization and embryo tansfer (IVF-ET) present a diagnostic and therapeutic dilemma. As the possibility of an ectopic tubal pregnancy can not be excluded with certainty, these patients are often subjected to surgical intervention in an attemptto establish a diagnosis. The efficacyofthis diagnostic approach was evaluated in 5 patients with documented tubal disease who had persistent but low serum levels of hcg. Two had had previous ectopic pregnancies, and 3 had undergone IVF-ETfortubal disease. All patients were, therefore, at increased risk for ectopic pregnancy. The duration of followup ranged from 48 to 111 days. The range of peak serum levels of {J-hCG was mlu/ml. None of the patients presented with any significant signs and symptoms, and in none was a viable pregnancy delineated by ultrasound. Four of the five patients underwent diagnostic curettage without identification of products of conception. A diagnostic laparoscopy was then performed but no tubal pregnancy identified. Although the etiology of the low but persistent elevation of hcg could not be determined, hcg reached undetectable levels in all five patients during the observation period. These patients with previous ectopic pregnancies and/or following IVF-ET constitute a specific group in which monitoring is instituted at an early stage. The appearance of low but persistent hcg titers may represent a failing intrauterine or extrauterine pregnancy. In our experience, conventional diagnostic modalities (D & C and laparoscopy) were not helpful in establishing the diagnosis. Therefore, in the absence of symptoms, we recommend a conservative approach with close observation but without surgical intervention. 031 FACTORS ASSOCIATED WITH SUCCESSFUL REVERSAL OF TUBAL STERILIZATION. M. M. Davis, M. K. Shepard, Dept. of Ob/Gyn, Indiana University Medical Center, Indianapolis, IN. In order to help patients decide between in vitro fertilization (IVF) and tubal anastomosis for the achievement of pregnancy after tubal sterilization, a critical appraisal of factors reportedly associated with successful tubal sterilization is necessary. These factors include tubal length greater than 4 cm after anastomosis, interval between sterilization and reversal of less than 5 years, age between 25 and 39 years, operating time less than 150 minutes, sterilization by mechanical means rather than electrocoagulation, and isthmic-isthmic anastomosis. The outcome of sterilization reversal in 50 women who underwent reconstructive surgery between July 1982 and December 1986 was evaluated with respect to the preceding factors. Twenty-six women conceived a total of 38 times. The average interval between sterilization and first conception was 6.5 months (range months). Conception occurred in 13 of 27 (48%) of women who had been sterilized by tubal coagulation and 13 of 23 (58%) who were sterilized by mechanical means. Of the 38 pregnancies there were 4 ectopics, 8 spontaneous abortions and 26 either delivered or ongoing. Age, interval between sterilization and reversal, operating time, and overall tubal length greater than 4 cm were not significantly different between the successful and the unsuccessful group. Anastomosis site was the single most important factor. The pregnancy rates are as follows: isthmic-isthmic 9/1 0 (90%), isthmic-cornual 8/12 (67%), ampullary-ampullary 2/3 (67%), ampullary-isthmic 4/12 (33%), ampullary-cornuai3/11 (18%), isthmic-fimbrial 0/2 (0%). These data suggest that luminal congruence between anastomosed segments plays a significant role in determining successful outcome and that women who have marked luminal disparity between segments may be better served by IVF than tubal anastomosis. 14 Abstracts

5 032 A PROSPECTIVE RANDOMIZED STUDY COMPARING THE TECHNIQUE OF LAPAROSCOPY (LSC) AND LAPAROTOMY (LAP) FOR LINEAR SALPINGOSTOMY (LS) IN THE MANAGEMENT OF UNRUPTURED ECTOPIC PREGNANCY (UEP). P. D. Silva, G. F. Rosen, M. Vermesh, A. L. Stein, J. M. Vargyas, R. P. Marrs, Dept. of Ob/Gyn, Univ. of So. California, Los Angeles, CA. The purpose of the study is to compare the parameters of morbidity, cost, length of hospital stay, tubal patency, and pregnancy outcome in a prospective randomized fashion between 2 groups of patients undergoing LS for UEP by LSC versus LAP. The following is a preliminary report of the first 20 patients entered into the study. Entry criteria included age> 18, UEP < 6cm, desireforfuture fertility, stable vital signs, and admission HCT > 30%. All patients signed an approved informed consent prior to LSC. Randomization occurred at LSC after the UEP was visualized. LS was performed by unipolar fine cautery. Follow up study included weekly BHCG titers and a hysterosalpingogram (HSG) at 3 months. Patients in the LSC group (n = 11) and LAP group (n = 9) were similar with respect to age (28 vs 27), gravity(2.1 vs 3), parity (0.4 vs 1.6), initial HCT (38% vs 37%), and initial BHCG titers (3579 vs 1813). All patients except one in each group had a hemoperitoneum. All UEP's were in the ampulla, or atthe ampullary-isthmic junction except for one isthmic UEP in the LSC group. A LS was achieved in all patients in the LSC group and none required LAP for hemostasis or retained products of conception. Patients in the LSC and LAP group had similar post operative Hcts (34 & 30) and delta Hcts (3.3 vs 3.9). The length of hospital stay (1.2 days vs 3.2 days), time needed for recuperation and cost to the patient were significantly lower in the LSC group (p 0.001). The only postoperative complication was a wound infection in the LAP group. Patients are currently undergoing HSGs. To date 3 of 4 demonstrated patency in the operated tube. The preliminary data suggests that LSC salpingostomy is a safe and efficient procedure. As the study proceeds, comparison between the 2 groups will be made with respect to tubal patency and pregnancy outcome. 033 DIAGNOSIS AND TREATMENT OF CORNUAL OBSTRUCTION BY TRANSCERVICAL COAXIAL RETROGRADE CANNULATION. M. J. Novy, A. S. Thurmond, C. T. Uchida, J. Rosch, Depts. of Ob/Gyn and Diagnostic Radiology, Oregon Health Sciences University, Portland, OR. Conventional HSG or laparoscopy may not differentiate cornual spasm from true obstruction. HSG had a 50% false positive rate for interstitial fallopian tube obstruction (IFTO) which was unrelieved by /J-agonists. We used fluoroscopically guided selective salpingography, and hysteroscopic retrograde cannulation to evaluate IFTO. Thirteen patients with IFTO had selective salpingography by fluoroscopic placement into the cornua of a modified Foley catheter. If tubal patency was not demonstrated by injection of Renografin 60 (ostial salpingogram) then a 3 Fr. Teflon cannula and soft-tipped flexible guidewire (0.018 or inches in diameter) were introduced coaxially and the guidewire advanced into the isthmoampullary portion of the tube or until resistance was met. Patency was confirmed by injection of contrast medium (intratubal salpingogram). Cornual patency was established by ostial salpingography in 6 patients and after retrograde cannulation in 5. In 6 other patients with suspected pelvic adhesions in addition to IFTO, interstitial patency was established in 4 by hysteroscopic coaxial retrograde cannulation with simultaneous direct observation of the fallopian tube by laparoscopy. Six patients with cornual occlusion and Asherman's syndrome had combined retrograde cannulation of the interstitial tube, hysteroscopic resection of adhesions, and microsurgical cornual-isthmic anastomosis; 3 pregnancies resulted. We conclude: Selective salpingography and retrograde cannulation of the proximal oviduct are promising techniques for the diagnosis and treatment of cornual occlusion. Abstracts 15

6 034 INDUCTION OF OVULATION AFTER OVARIAN SURGERY. J. A. Jakowicki, Dept. of Ob/Gyn, Academy of Medicine, Lublin, Poland. The influence of ovarian surgery, except the wedge resection, on the future ovulation is unknown. We treated 24 women with the anovulatory cycles, aged 21 to 34, who were operated on because of benign ovarian tumor (14 cases) or endometriosis treated afterwards with MPA or danazol (10 cases). Depending on the extent of the operation performed 1 to 4 years ago, in 10 women with unilateral adnexectomy (four of them with the endometrial cyst) after clomiphene -HCG therapy the presence of the corpus luteum, confirmed by BBT, vaginal cytology and serum progesterone (7.3 and 10.2 ng/ml) were noted in two patients only. The mean serum FSH (± SED) before treatment was 6.2 ± 1.2 mu/ml and LH 12.2 ± 4.4 mu/ml. Only in four patients the mid-cycle serum estradiol was above 200 pg/ml. In 14 women after conservative operations Iten of them because of endometriosisl the ovulation was obtained in 6 cases and two patients became pregnant and delivered spontaneously. The mean initial serum FSH (10.0 ± 4.1 muiml) and LH (14.4 ± 6.8 mu/ml) did not differ statistically in comparison with the previously mentioned group. In the case of benign ovarian tumors the ovulation was obtained in 30% but in the case of endometriosis in 21.4% only. The repeated therapy with HMG-HCG in 8 unresponding patients was not efficacious in spite ofthe increase of serum estradiol above 100 pg/ml. The induction of ovulation after ovarian surgery remains a serious problem in ovarian sterility. Monday, September 28, 1987 Session 5-Advances In Andrology 2:00 P.M. to 5:00 P.M. 035 CRYOPRESERVATION OF HAMSTER OOCYTES FOR THE SPERM PENETRATION ASSAY. Z. Binor, R. Rawlins, S. Sachdeva, Sect. of RE/I, Rush Medical College, Chicago, IL. Zona-free hamster ova penetration by human spermatozoa is clinically used as a bioassay for assessment of male factor. The assay requires 3 days hormone stimulation prior to collection of oocytes and large numbers of animals must be maintained in the vivarium. We evaluated cryopreservation of hamster oocytes for long-term storage in liquid nitrogen. Oocytescollected from oviducts of superovulated (30 IU PMS, 30 IU HCG) female hamsters were denuded in BWW medium containing 8.0 mg/ml serum albumin and 1.0% hyaluronidase. Zona-intact ova, free of cumulus cells were cryopreserved. The protocol was modified from Mohr et al. (J. IVF-ET, 2:1 1985). Dimethylsulfoxide (DMSO) in phosphate buffered saline (PBS), supplemented with 10% heat inactivated and filtered human serum was used as a cryoprotectant. Oocyte were dehydrated by one step equilibration in 1.5 M DMSO, then loaded into 500 UL plastic straws, and placed in a Planer R204 cell freezer. Oocytes were cooled at 1 C/min to - 6 C, seeded automatically over 15 min, cooled at C/min to - 80 C and plunged into liquid nitrogen. After 6 weeks storage, oocytes were thawed at 8 C/min to RT and rehydrated by direct placement in BWW for the assay. Zonae pellucidae were removed by short exposure to a 1.0% trypsin solution. Ova were inseminated with 3-5 million motile sperm/ml. The penetration rate of frozen-thawed oocytes was compared to fresh ova. The total number of ova tested was 271 (110 fresh and 161 cryopreserved). Both groups were penetrated at equivalent rates: 70/100 (63.6%) fresh and 109/161 (67.7%) frozen. The difference was not statistically significant (X2 = 0.048, P>0.05). We conclude that long term cryopreservation of hamster ova: 1) does not affect assay results, 2) provides immediate access to the assay and 3) reduces assay time. 036 FAILURE OF FERTILIZATION IN IVF. THE "OCCULT" MALE FACTOR. S. Oehninger, A. A. Acosta, T. Kruger, L. L. Veeck, J. Flood, H. W. Jones, Jr., Jones Institute of Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA. Failure of fertilization in patients undergoing IVF deserves extensive analysis in order to be able to predict success or failure of this therapeutic modality. Consequently, we retrospectively studied 52 couples in whom no fertilization occurred during Norfolk Series 18 to 25 (583 patients, 10671VF attempts, 943Iaparoscopies). In 13.4% of the patients an intrinsic or stimulation-clerived oocyte problem could account for the lack of fertilization; in 57.7% of the cases one or several sperm abnormalities were found, and a combination of oocyte and sperm abnormalities were present in 13.4% of the patients. Furthermore, in 15.4% of the cases no obvious cause could explain failed fertilization. However, 7 out of the 8 male patients in this final group need to be reassessed in order to conclusively assign them to the category of male factor or idiopathic failed fertilization. After reassessing sperm morphology with the new criteria presently being used in our laboratory we were able to diagnose sperm abnormalities in more than 70% of the male population. This is a remarkable finding when we take into consideration that the initially diagnosed incidence of male factor abnormalities in the whole group was only 40.3%. Therefore the role that these variables can play in IVF is emphasized and we stress that a thorough male evaluation can offer valuable information so as to prepare the patient and the clinician on the possible outcome of IVF. 16 Abstracts