FERTILITY AND STERILITY Cpyright 99 The American Fertility Sciety Vl., N., May 99 Printed n acid-free paper in U.S.A. Adhesin frmatin after laparscpic surgery in tubal pregnancy: a randmized trial versus lapartmy* Per Lundrff, M.D.t Mats Hahlin, M.D., Ph.D. Bjrn Kallfelt, M.D., Ph.D. Jane Thrburn, M.D., Ph.D. B Lindblm, M.D., Ph.D. Department f Obstetrics and Gyneclgy, University f Gtebrg, Gtebrg, Sweden Objective: Wmen with ectpic pregnancy (EP) wh have been perated n by laparscpy are thught t have imprved subsequent fertility, prbably because f less adhesin frmatin. We aimed t evaluate the adhesin frmatin after laparscpy as cmpared with lapartmy in a randmized trial. Design: One hundred five patients with tubal pregnancy were stratified with regard t age and risk factrs and randmized t surgery by laparscpy r lapartmy. T evaluate adhesin frmatin and tubal status, 7 patients with strng desire f pregnancy underwent a secnd-lk laparscpy. The adhesin status at the ipsilateral and cntralateral at primary surgery was cmpared with the status at secnd-lk laparscpy. Results: Patients perated n by lapartmy develped significantly mre adhesins at the perated than patients perated n by laparscpy (P <.). Substantially mre patients in the lapartmy grup underwent adhesilysis at secnd-lk laparscpy than did patients in the laparscpy grup. Tubal patency did nt differ between the grups. Cnclusins: Laparscpic treatment f EP results in less impairment f the pelvic status cmpared with cnventinal cnservative surgery. Fertil Steril :9, 99 The laparscpic apprach fr treatment f ectpic pregnancy (EP) has suggested imprved fertility, maybe n the basis fless adhesin frmatin because laparscpy avids drying f the serus peritneal membrane.! Yet, a previus retrspective study frm ur clinic did nt reveal any differences in the extent f adhesin frmatin r tubal patency after varius surgical methds, including laparscpic surgery. Our intentin with the present cntrlled investigatin was t study the extent f pelvic adhesin frmatin after laparscpic treatment f EP as cmpared with cnventinal surgery, evaluated by Received September, 99; revised and accepted January, 99. * Supprted by grant frm The Swedish Medical Research Cuncil, Sweden, and by the Gtebrg Medical Sciety, Gtebrg, Sweden. t Reprint requests: Per Lundrff, M.D., Department f Obstetrics and Gyneclgy, University f Gtebrg, Sahlgrenska Hspital, S- Gtebrg, Sweden. Vl., N., May 99 a secnd-lk laparscpy in a prspective randmized trial. T ur knwledge, n cntrlled trial cncerning this imprtant matter has been cnducted previusly. MATERIALS AND METHODS During a -year perid between May 97 and June 99, wmen with tubal pregnancy, stratified accrding t age and risk determinants, were randmized in a prspective trial t surgery by laparscpy r lapartmy. The design f the study was described recently. In 7 cases with a desire fr pregnancy (laparscpy n = ; lapartmy n = ) a secnd-lk laparscpy was perfrmed weeks ( t 9) after primary surgery. In the remaining patients, n secnd-lk laparscpy was perfrmed. Eighteen f these had n desire fr pregnancy, 9 cnceived befre planned secnd-lk laparscpy, and were recmmended in vitr fertilizatin after EP surgery because f extensive pelvic adhesins. Lundrff et al. Adhesins after ectpic pregnancy 9
In the laparscpy grup, all patients had a linear salpingtmy perfrmed, which was left pen fr secndary healing. In five cases, additinal lysis f adhesins was undertaken, in ne case n the ipsilateral and in fur ther cases n the cntralateral (Table ). In the lapartmy grup (n = ), patients had a linear salpingtmy perfrmed, were treated with "milking" f the tube, patients had a tubal resectin, and had a salpingectmy perfrmed. Further, patient underwent salpingectmy at a secnd interventin because f bleeding. Three patients were subjected t lysis f adhesins n the ipsilateral and tw thers n the cntralateral (Table ). In all cases, tubal surgery was preceded by vaspressin injectin f IU in ml f saline int the messalpinx t avid bleeding. In case f laparscpy, salpingtmy was perfrmed using a diathermy knife and a suctin/irrigatin instrument (Aquapuratr, Wisap, Sauerlach, Germany) via inserted separate trcars in the suprapubic regin. In case f lapartmy an atraumatic technique, including nnwven spnges and peritneal lavage was used. Bth at EP surgery and at secnd-lk laparscpy, the anatmic cnditins f the pelvis were registered n a preprinted frm and lysis f adhesins was nted. At secnd-lk laparscpy, tubal patency was tested by dye slutin. The affected tube was nt scred at EP surgery because we fund it dubius t make a prper classificatin and cmpare a pregnant tube accurately with the nnpregnant rgan. The adhesins n bth s and the tubal status n the cntralateral were evaluated, thus cnstituting the "adhesin and tubal scre," bth at EP surgery and at secnd-lk laparscpy. The evaluatin was perfrmed by using a mdificatin fthe scre system described by Mage et a. (Table ). Grade implies nrmal cnditin and grade the mst severe damage. T study impairments r imprvements, a scre change was calculated fr each patient. Statistics Cmparisns were perfrmed by Fisher's twd permutatin test. A P value <. was cnred t be statistically significant. RESULTS In cmparisn between the surgical prcedures, imprvements f adhesins and f tubal status were regarded as an unchanged status because imprvement was cnred a result f lysis f adhesins at primary surgery and nt a cnsequence f the surgical methd per se. Presentatin f the Adhesins The distributin f adhesin scres at the time fr EP surgery and secnd-lk surgery fr the tw surgical methds is presented in Table. On the Table Adhesins and Lysis f Adhesins in Patients Operated n by Laparscpy and at Time fr EP Surgery and Secnd-lk Laparscpy N. f cases bilaterally free f adhesins Laparscpy (n = ) (n = ) EP surgery ()" () Secnd-lk laparscpy () 9 () Ipsilateral Cntralateral Ipsilateral Cntralateral N. f cases with diagnsed periadnexal adhesins Laparscpy Adhesilysis Laparscpy Recurrence f adhesins at secnd-lk laparscpy Laparscpy " Values in parentheses are percents. 9 Lundrff et al. Adhesins after ectpic pregnancy Fertility and Sterility
Table Scring System a Adhesin scring system b Ovary Prximal tube Distal tube Tubal scring system' Infundibulum Nrmal Phimsis Sactsalpinx Ampullary tubal wall Nrmal Thin Thick r rigid Patency / / a Mdified frm Mage et ai.' b Grade (absence): ; grade (mild): t 9; grade (mderate): t ; grade (severe): >., Grade (absence): t ; grade (mild): ; grade (mderate): 7 t ; grade (severe): t. Surface invlved / / Scre / Yes/n / / ipsilateral in the laparscpy grup, an impairment was nted in patients (%). Twenty-five patients (%) had an unchanged status, and patient (%) had an imprved status. On the cntralateral, patients (%) had an impaired status, had an unchanged status (7%), and had an imprved status (%) (Fig. ). All patients with imprvement f the status had adhesilysis perfrmed at EP surgery. In the lapartmy grup n the ipsilateral, patients (%) had an impaired status, patients (%) had status qu, and patients (%) were imprved, bth f whm had adhesilysis perfrmed at EP surgery. On the cntralateral, patients had impairment f the status (%), 9 patients status qu (9%), and n patient imprved the status (Fig. ). Patients perated n by laparscpy develped less adhesins than thse patients treated by lapa- Vl., N., May 99 rtmy. On the ipsilateral, the difference was statistically significant (P <.). In bth surgical grups, recurrence f adhesins was nticed in f patients (%) wh had adhesilysis perfrmed either n ipsilateral r cntralateral (Table ). Yet, in the case f laparscpy, the adhesins were nt as severe as befre lysis. At EP surgery, % f the patients in the laparscpy grup and % in the lapartmy grup presented with n adhesins at all. At secnd-lk laparscpy, these frequencies were reduced t % and %, respectively (Table ). Presentatin f Tubal Status The distributin f the tubal scres (cntralateral ) is seen in Table. Impairment f the tubal status was fund in ne f patients (%) in the laparscpy grup. An unchanged status was seen in f patients (9%). In patients (7%), wh had lysis f adhesins perfrmed at primary surgery, imprvement f the status was nticed (Table and Fig. ). Three patients were nt evaluated because f previus salpingectmy. Impairment f the status in the lapartmy grup was fund in f 9 patients (%), and f 9 patients (%) had an unchanged status with n imprvement seen. Three patients were nt evaluated because f previus salpingectmy (Table and Fig. ). There was n statistically significant difference between the surgical techniques with regard t the tubal scre. Tubal Patency Laparscpy Grup On the ipsilateral, 9 f patients were evaluated fr patency by dye slutin. In f 9 Percent laparscpy *** lapartmy Figure The percentage distributin f impairments in adhesin and tubal cnditins between EP surgery and secnd-lk laparscpy. Laparscpy grup (n = ). grup (n = )., impairment f adhesins n the ipsilateral. D, impairment f adhesins n the cntralateral. ~, impairment f the tubal status n the cntralateral. ***, P <.. Lundrff et al. Adhesins after ectpic pregnancy 9
Table Adhesin and Tubal Scres in Patients Operated n by Laparscpy and in Patients Operated n by at Time fr EP Surgery and Secnd-lk Laparscpy EP surgery Secnd-lk laparscpy Ipsilateral Cntralateral Ipsilateral Cntralateral Laparscpy (n = ) Adhesin scre 7 Tubal scre b (n = ) Adhesin scre 7 Tubal scre b a Grade, n adhesins; grade, mst severe adhesins. () () 9 () () () b Values in parentheses indicate the number f patients nt evaluated fr tubal scres because f previus salpingectmy. cases (7%), the tube was patent. Tw patients culd nt be evaluated fr technical reasns. In 7 f 9 patients (%) the tube was bstructed. On the cntralateral, 7 f patients were examined, and patency was fund in f 7 patients (7%). Fur patients culd nt be evaluated; because f previus salpingectmy and fr technical r medical reasns. In 7 f 7 patients, (%) the tube was bstructed. Grup On the ipsilateral, f patients were examined, and patency was fund in f patients (%). In thse patients nt examined, previusly had a salpingectmy perfrmed, had severe adhesins, and because f nging menstrual bleeding. In f patients ( %), the tube was ccluded. On the cntralateral, f patients were examined, and patency was fund in f (7%) patients. Eight patients culd nt be evaluated, because f previus salpingectmy and because f technical r medical factrs. In patients (%), the tube was ccluded. There was n statistically significant difference between the tw surgical methds with regard t patency neither n the ipsilateral nr n the cntralateral. In five cases perated n by laparscpy and in ne case perated n by lapartmy, fluid leakage frm the salpingtmy was nticed. DISCUSSION Periadnexal adhesin frmatin is suggested as an imprtant factr in infertility after pelvic surgery,fh! and evaluatin f the etilgy and preventin f adhesin frmatin have been the majr gal fr many investigatins. 9,l T avid tissue ischemia and cnsequently adhesin frmatin in the peratin field, Levinsn and Swlin 9 advcated nntraumatic techniques with bldless entry int the abdminal cavity by use f electrsurgery, peritneal lavage, and cmplete excisin f diseased tissue. It has been suggested that laparscpic surgery culd reduce the degree f adhesin frmatin because f less peritneal damage. Recently, Mecke et aly fund that laparscpic treatment f EP des nt cmpletely prevent the develpment f pstperative adhesins. Furthermre, a retrspective reprt frm ur clinic did nt demnstrate differences in the develpment f adhesins in patients perated n by laparscpy cmpared with cnservative lapartmy. Mecke et al. ll fund that cncmitant adhesilysis reduces the degree f severity f recurring adhesins. This is in agreement with ur results because we fund that cncmitant adhesilysis reduces the recurrence f adhesins bth in patients treated by laparscpy and by lapartmy. Yet, in case flaparscpy, the degree f severity f the adhesins was reduced. One might argue that it wuld be mre prper t cmpare adhesin frmatins nly in thse patients wh underwent salpingtmy. Hwever, this was nt the intentin with the study and wuld jepardize the nature f this randmized trial. The timing f the secnd-lk laparscpy after fertility surgery is a matter f cntrversy. An early secnd lk, i.e., after t weeks simplifies adhesilysis, but it is nt clear t what extent new adhesins are frmed. A late laparscpy, i.e., after t mnths prbably implies that the prcess f adhesin frmatin has been cmpleted and this wuld give a mre accurate estimatin f the scre change. A further expansin f the time interval t 9 Lundrff et al. Adhesins after ectpic pregnancy Fertility and Sterility
the secnd-lk laparscpy wuld increase the risk f a new ectpic. Fr these reasns, we intended t perfrm the secnd-lk laparscpy within weeks. Laparscpic management f tubal pregnancy in this study caused significantly fewer adhesins pstperatively n the treated. In additin, fewer adhesins were seen n the cntralateral adnexa, but the degree was nt significantly different frm the lapartmy grup. Adhesilysis at EP surgery is a useful methd fr reducing the frmatin f pstperative adhesins. Whether this reductin will increase subsequent fertility in such patients has nt been ascertained. REFERENCES. Bruhat MA, Manhes H, Mage G, Puly JL: Treatment f ectpic pregnancy by means f laparscpy. Fertil Steril :, 9. Lundrff P, Thrburn J, Lindblm B: Secnd-lk laparscpy after ectpic pregnancy. Fertil Steril :, 99. Lundrff P, Thrburn J, Hahlin M, Kiillfelt B, Lindblm B: Evaluatin f mdern surgical management f tubal pregnancy. A randmized prspective clinical trial f laparscpy versus lapartmy. (Abstr. ) Presented at the Seventh Wrld Cngress n Human Reprductin, Helsinki, Finland, June t July, 99. Published by Kirjapain Tap Oy, Helsinki, in the Prgram Supplement f the VII Wrld Cngress n Human Reprductin, 99. Mage G, Puly J-L, Buquet de Jliniere J, Chabrand S, Riualln A, Bruhat M-A: A preperative classificatin t predict the intrauterine and ectpic pregnancy rates after distal tubal micrsurgery. Fertil Steril:7, 9. Bradley JW: Distributin-Free Statistical Test. Englewd Cliffs, New Jersey, Prentice Hall, 9, p. Brnsn RA, Wallach EE: Lysis f periadnexal adhesins fr crrectin f infertility. Fertil Steril :, 977 7. Caspi E, Halperin Y, Bukvsky I: The imprtance f peri adnexal adhesins in tubal recnstructive surgery fr infertility. Fertil Steril :9, 979. Diamnd E: Lysis f pstperative pelvic adhesins in in-. fertility. Fertil Steril :7, 979 9. Levinsn CJ, Swlin K: Pstperative adhesins; etilgy, preventin and therapy. Clin Obstet Gynecl :, 9. Myhre-Jensen, Larsen SB, Astrup T: Fibrinlytic activity in sersal and synvial membranes. Arch Pathl :, 99. Mecke K, Semm K, Freys I, Argirin CH, Gent H -I: Incidence f adhesins in the true pelvis after pelviscpic perative treatment f tubal pregnancy. Gynecl Obstet Invest :, 99. Trimbs-Kemper TCM, Trimbs JB, van Hall EV: Adhesin frmatin after tubal surgery: results f the eighth-day laparscpy in patients. Fertil Steril :9, 9 Vl., N., May 99 Lundrff et ai. Adhesins after ectpic pregnancy 9