ABSORBABLE GELATIN
Report
- Report Number
- 1810189-2020-00035
- Event Type
- Injury
- Date Received
- April 10, 2020
- Report Date
- March 24, 2020
- Manufacturer
- PFIZER, INC. (DEVICE)
- Product Code
- LMF
- PMA / PMN Number
- 18-286
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- JA
- Reporter Occupation
- OTHER
Narratives
THE PRODUCT DESCRIPTION WAS FOR GELFOAM STERILE SPONGE SIZE 100 X 1. DEVICE MALFUNCTION WAS REASONABLY SUGGESTED. THE SEVERITY OF HARM RANKING WAS A S4. THE FOLLOWING WAS THE DESCRIPTION OF COMPLAINT: PRODUCT COMPLAINT EXCHANGE: [PRODUCT COMPLAINT EXCHANGE: [AERS#: (B)(4); SUSPECT: ABSORBABLE GELATIN; EVENT: 10 CASES OF UTERINE INFECTIONS (16.2%)] [AERS#: (B)(4); SUSPECT: ABSORBABLE GELATIN; EVENT: 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED]. THE FOLLOWING WAS THE ROOT CAUSE ANALYSIS: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE SITE PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER SITE. THE FOLLOWING WAS THE CONCLUSION: THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. THE COMPLAINT HAS BEEN ESCALATED TO SAFETY FOR EVALUATION OF REGULATORY REPORTABILITY. FURTHER ACTION BY PFIZER MANUFACTURING SITE IS NOT REQUIRED.
ATTACHMENT: [1810189-20200410182511_LIT.PDF].
EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE [OFF LABEL USE], EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE INDICATION [PRODUCT USE IN UNAPPROVED INDICATION], 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED [OVARIAN DISORDER]. NARRATIVE: THIS IS A LITERATURE REPORT FROM THE JAPANESE JOURNAL OF RADIOLOGY, 2020, VOL 38 (3); PP 240-247 DOI (10.1007/S11604-019-00907-2). ENTITLED UTERINE ARTERY EMBOLIZATION FOR POSTPARTUM AND POSTABORTION HEMORRHAGE: A RETROSPECTIVE ANALYSIS OF COMPLICATIONS, SUBSEQUENT FERTILITY AND PREGNANCY OUTCOMES. THIS AUTHOR REPORTED DIFFERENT EVENTS FOR TWELVE PATIENTS. THIS IS THE ELEVENTH OF TWELVE REPORTS. A FEMALE PATIENT OF AN UNSPECIFIED AGE STARTED TO RECEIVE GELATIN SPONGE (GS), VIA AN UNSPECIFIED ROUTE OF ADMINISTRATION BY PUMPING METHOD FROM AN UNSPECIFIED DATE AT UNKNOWN DOSE (INJECTION) FOR UTERINE ARTERY EMBOLIZATION (UAE) DUE TO POSTPARTUM OR POSTABORTION HEMORRHAGE. THE PATIENT'S MEDICAL HISTORY AND CONCOMITANT MEDICATIONS WERE NOT REPORTED. THE PATIENT EXPERIENCED OVARIAN DYSFUNCTION AFTER EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE. THE ACTION TAKEN IN RESPONSE TO THE EVENTS FOR ABSORBABLE GELATIN WAS UNKNOWN. THE PATIENT OUTCOME WAS UNKNOWN. WE INVESTIGATED FACTORS THAT INFLUENCE COMPLICATIONS AFTER UAE IN PATIENTS WITH REPRODUCTIVE DEMANDS, BASED ON PATIENT BACKGROUNDS AND ANGIOGRAPHIC ENDPOINTS. FURTHERMORE, WE STUDIED FUTURE PREGNANCY OUTCOMES, ESPECIALLY IN PATIENTS UNDERGOING INFERTILITY TREATMENT. MATERIALS AND METHODS: THIS RETROSPECTIVE STUDY WAS APPROVED BY THE INSTITUTIONAL REVIEW BOARD OF BOTH INSTITUTIONS. INFORMED CONSENTS FOR UAE WERE OBTAINED FROM ALL PATIENTS. SUBJECTS INCLUDED IN THIS STUDY WERE 75 WOMEN FROM 79 CONSECUTIVE SESSIONS FROM TWO TERTIARY REFERRAL CENTERS. THESE WOMEN UNDERWENT UAE FOR POSTPARTUM OR POST-ABORTION HEMORRHAGE BETWEEN 2008 AND 2017. CASES OF HEMORRHAGE DUE TO MALIGNANCY WAS EXCLUDED AND THE CASES WITHOUT DETAILED ANGIOGRAM IMAGES OR CLINICAL INFORMATION WERE ALSO EXCLUDED. FINALLY, 59 PATIENTS WHO UNDERWENT 62 SESSIONS OF UAE IN TOTAL WERE ELIGIBLE, WHICH INCLUDING PRIMARY POSTPARTUM HEMORRHAGE IN 19 SESSIONS, SECONDARY POSTPARTUM HEMORRHAGE IN 5 SESSIONS, POST-ABORTION HEMORRHAGE IN 27 SESSIONS, CERVICAL PREGNANCY IN 11 SESSIONS. DATA ON PATIENT CHARACTERISTICS SUCH AS AGE, PREGNANCY HISTORIES, PAST ILLNESS INCLUDING UTERINE SURGERY SUCH AS CAESAREAN SECTION (C/S), D&C AND HYSTEROSCOPIC RESECTION, HISTORY OF INFERTILITY TREATMENT AND DESIRE OF CHILDBEARING, BACKGROUND DISEASES THAT RESULTED IN RECEIVING UAE, HISTORY OF MASSIVE HEMORRHAGE, AND PREOPERATIVE HEMOGLOBIN LEVEL WERE EXTRACTED FROM THE MEDICAL RECORDS OF THE TWO MEDICAL CENTERS. WE DEFINED MASSIVE HEMORRHAGE AS A STATE WITH A SHOCK INDEX OF MORE THAN 1.0, OR WITH EXTRAVASATION DEMONSTRATED BY CONTRAST-ENHANCED COMPUTED TOMOGRAPHY OR DEMONSTRATED ANGIOGRAPHICALLY DURING UAE. EMBOLIC MATERIALS, DEGREE OF EMBOLIZATION OF THE UTERINE ARTERY, AND VISUALIZATION OF UOA ON THE UTERINE ANGIOGRAPHY BEFORE EMBOLIZATION WERE EVALUATED AS ANGIOGRAPHIC ITEMS. COMBINATION TREATMENT, INCLUDING THE CASES PERFORMED D&C OR TRANSCERVICAL RESECTION AFTER UAE, WAS ALSO RECORDED. AS PRIMARY OUTCOMES, SUBSEQUENT PREGNANCY AND PREGNANCY COMPLICATIONS SUCH AS PLACENTA ACCRETA WERE CONSIDERED PRIMARY OUTCOMES. WITH REGARDS TO CASES OF PREGNANCY AND MISCARRIAGE, CUMULATIVE NUMBER OF CASES WAS ALSO DESCRIBED. AS SECONDARY OUTCOMES, ACUTE COMPLICATIONS OF UTERINE INFECTIONS AND OVARIAN DYSFUNCTION WERE EVALUATED. WE DEFINED UTERINE INFECTION AS A CONDITION WITH PROLONGED FEVER ACCOMPANIED BY LOWER ABDOMINAL PAIN, CHILLS, AND SHIVERING CURED BY ADMINISTRATION OF INTRAVENOUS ANTIBIOTICS. CASES THAT COULD BE RETROSPECTIVELY REGARDED AS POST-EMBOLIZATION SYNDROME, NON-INFECTION CONDITIONS PRESENTING AS TRANSIENT FEVER AND LOWER ABDOMINAL PAIN, WERE CAREFULLY EXCLUDED. OVARIAN DYSFUNCTION WAS BASED ON SERUM FOLLICULAR STIMULATING HORMONE (FSH) ELEVATION OF MORE THAN 40 MIU/ML ACCORDING TO THE DEFINITION GIVEN IN A PREVIOUS RANDOMIZED CONTROLLED TRIAL ABOUT OVARIAN RESERVE AFTER UAE FOR PATIENTS WITH LEIOMYOMAS. IN ADDITION, RESUMPTION OF REGULAR MENSES WAS REGARDED AS NORMAL OVARIAN FUNCTION. THE DEGREE OF EMBOLIZATION OF THE UA WAS CLASSIFIED BY A SCORE FROM 0 TO 2 DEPENDING ON THE STASIS OF THE INTRAUTERINE BRANCH OF THE UA. SCORE 0 WAS DEFINED AS THE STATE IN WHICH EVEN A SMALL AMOUNT OF FLOW FROM THE INTRAUTERINE BRANCH OF THE BILATERAL UA REMAINED. SCORE 1 WAS DEFINED AS STASIS OF FLOW FROM THE INTRAUTERINE BRANCH ON UNILATERAL SIDE. SCORE 2 WAS DEFINED AS STASIS ON BOTH SIDES OF THE INTRAUTERINE BRANCHES, AND FLOW MAINTAINED FROM A HORIZONTAL OR ASCENDING SEGMENT OF THE UAS. IN ADDITION, VISUALIZATION OF THE UOA BEFORE EMBOLIZATION WAS ALSO EVALUATED. IVR PROCEDURE: IN ALMOST CASES, A 5-F SHEATH (MEDIKIT, TOKYO, JAPAN) WAS GENERALLY INSERTED FROM THE UNILATERAL FEMORAL ARTERY THROUGH WHICH A 5-F PIG TAIL CATHETER (FANSAC IV, TERUMO-CLINICAL SUPPLY, GIFU, JAPAN) WAS ADVANCED TO ABDOMINAL AORTA PRIOR TO SELECT UA. PELVIC AORTOGRAPHY WAS PERFORMED TO ENSURE ARTERIAL ANATOMY, ESPECIALLY THE INVOLVEMENT OF NON-UA WAS CAREFULLY EVALUATED. AFTER SELECTIVE CATHETERIZATION OF EACH UA USING A 5FR COBRA SHAPED CATHETER WITH A GUIDE WIRE (0.035, ANGLE TYPE; RADIFOCUS, TERUMO, TOKYO, JAPAN) AND A STANDARD COAXIAL 2.8F-MICROCATHETER SYSTEM (RENEGADE, BOSTON SCIENTIFIC CORP.), EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE BY PUMPING METHOD. AFTER BILATERAL UA EMBOLIZATION, OBSTETRICIAN EXAMINED AND CONFIRMED HEMOSTASIS CLINICALLY. IF ACTIVE BLEEDING PERSISTS, THE OTHER FEEDING ARTERY WAS DETECTED AND EMBOLIZED. STATISTICAL ANALYSIS WE DIVIDED THE 62 CASES INTO TWO GROUPS BASED ON THE PRESENCE OF MASSIVE HEMORRHAGE AND 23 PATIENTS WHO HAD A DESIRE FOR CHILDBEARING WERE ALSO DIVIDED ACCORDING TO WHETHER THEY WERE UNDERGOING INFERTILITY TREATMENT OR NOT. R SOFTWARE (VERSION 3.4.1; R FOUNDATION FOR STATISTICAL COMPUTING, VIENNA, AUSTRIA) WAS USED FOR ALL STATISTICAL ANALYSES. CONTINUOUS VARIABLES ARE EXPRESSED AS THE MEAN +/- SD, AND CATEGORICAL VALUES ARE EXPRESSED AS NUMBERS AND FREQUENCIES. COMPARISON OF QUALITATIVE VARIABLES IN THE TWO GROUPS WAS PERFORMED USING FISHER'S EXACT TEST OR THE CHISQUARE TEST FOR INDEPENDENCE. COMPARISONS OF QUANTITATIVE VARIABLES IN THE TWO GROUPS WERE PERFORMED USING STUDENT'S T TEST. THE UA SCORES WERE COMPARED BETWEEN THE TWO GROUPS USING THE MANN-WHITNEY U TEST. THE COMPARISON OF UA SCORES WITH THE OCCURRENCE OF UTERINE INFECTION WAS ALSO ANALYZED USING THE MANN-WHITNEY U TEST. A P VALUE OF < 0.05 (TWO-TAILED) WAS CONSIDERED STATISTICALLY SIGNIFICANT. RESULTS TABLE 1 SHOWS PATIENT CHARACTERISTICS AND PRIMARY OUTCOMES. THE MEAN AGE WAS 34.1 +/- 6.5 YEARS. MOST OF CASES (49 CASES, 79.0%) HAD HISTORIES OF PREVIOUS UTERINE SURGERY SUCH AS C/S AND D&C. THE CAUSES OF BLEEDING INCLUDED PRIMARY POSTPARTUM HEMORRHAGE IN 19 CASES (25.8%), SECONDARY POSTPARTUM HEMORRHAGE IN 5 CASES (8.1%), POSTABORTION HEMORRHAGE IN 27 CASES (43.5%), CERVICAL PREGNANCY IN 11 CASES (17.7%). TEN OF THE 23 PATIENTS (43.5%) WITH A DESIRE OF CHILDBEARING UNDERWENT INFERTILITY TREATMENT. THERE WERE 27 CASES (43.5%) OF MASSIVE HEMORRHAGE. GELATIN SPONGE BY PUMPING METHOD WAS MAINLY USED AS THE EMBOLIC MATERIAL. IN ONE CASE WITH MASSIVE HEMORRHAGE, 20% NBCA WAS USED FOR RIGHT UA TO PREVENT EARLY RE-CANALIZATION, FOLLOWING BY GELATIN SPONGE INJECTION. IN ONE CASE OF RETAINED PRODUCTS OF PLACENTA (RPOC) COMBINED WITH ARTERIOVENOUS MALFORMATION, AN ABSOLUTE ETHANOL WAS USED TO ERADICATE NIDUS AND VENOUS SAC. BILATERAL UA WAS EMBOLIZED BY 0.5 ML ABSOLUTE ETHANOL FOR EACH INJECTION IN TOTAL 9 ML, FOLLOWED BY PUSHABLE METALLIC COIL EMBOLIZATION. IN TWO CASES OF VAGINAL LACERATIONS, MIDDLE COLIC ARTERY OR INTERNAL PUDENDAL ARTERY WAS ALSO EMBOLIZED IN EACH CASE, RESPECTIVELY. THE CLINICAL SUCCESS RATE OF UAE COMBINED WITH HYSTEROSCOPIC RESECTION OR D&C WAS 95.2% (59/62 CASES). THREE PATIENTS OF THEM RECEIVED TWO UAES; TWO PATIENTS FOR RELAPSED HEMORRHAGE BY CERVICAL PREGNANCY AND RPOC, THE OTHER ONE FOR A PLACENTAL ACCRETA AFTER EIGHT YEARS FROM PREVIOUS UAE. REGARDING THE UA SCORE, 43 CASES HAD SCORE 0, 13 CASES HAD SCORE 1, AND 6 CASES HAD SCORE 2. UOA WAS VISUALIZED IN 15 CASES (24.2%). UA SCORE WAS 0 IN ALL TWO CASES OF RELAPSED HEMORRHAGE. AFTER UAE, 10 CASES OF UTERINE INFECTIONS (16.2%) AND 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED. TWO OF THE PATIENTS WITH UTERINE INFECTION RESULTED IN SUBSEQUENT HYSTERECTOMY AND ONE PATIENT RESULTED IN ASHERMAN'S SYNDROME. IN 10 CASE WITH UTERINE INFECTION, GELATIN SPONGE WAS USED IN ALL CASES AND METALLIC COIL IN 1 CASE. THE UA SCORES WERE AS FOLLOWS: SCORE 0 FOR 5 CASES, SCORE 1 FOR 4 CASES, SCORE 2 FOR 1 CASE. THERE WAS NO DIFFERENCE OF UA SCORE WHETHER AN OCCURRENCE OF UTERINE INFECTION OR NOT (P = 0.297). PREGNANCY OUTCOMES INCLUDED 20 CUMULATIVE PREGNANCIES IN 14 PATIENTS, 12 LIVE BIRTHS IN 10 PATIENTS, AND 8 CUMULATIVE MISCARRIAGES. PREGNANCY RATE AND LIVE BIRTH RATE WERE 60.9% (14 OF 23 PATIENTS) AND 43.5% (10 OF 23 PATIENTS) RESPECTIVELY. THE DELIVERY ROUTE OF THE 12 LIVE BIRTHS WAS NORMAL SPONTANEOUS VAGINAL DELIVERY IN 7 PATIENTS AND ELECTIVE C/S IN 5 PATIENTS. REGARDING COMPLICATIONS AT BIRTH, FOUR PATIENTS HAD PLACENTA ACCRETA, ONE OF WHOM HAD SEVERE PERITONEAL ADHESION DURING ELECTIVE C/S AND ANOTHER HAD ATONIC BLEEDING. THE OCCURRENCE OF UTERINE INFECTION WAS SIGNIFICANTLY HIGHER IN THE GROUP WITH MASSIVE HEMORRHAGE THAN THAT IN THE GROUP WITHOUT (P = 0.014). COMPARING THE ANGIOGRAPHIC ENDPOINTS BETWEEN THE TWO GROUPS, NEITHER THE DIFFERENCE IN THE UA SCORE (P = 0.109), NOR THE DIFFERENCE IN THE VISUALIZATION OF THE UOA (P = 0.111) WAS SIGNIFICANT. IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT, PATIENTS UNDERGOING INFERTILITY TREATMENT WERE OLDER (MEAN AGE 36.3 VS. 30.1 P = 0.012). FOUR OF THE NINE NULLIPAROUS PATIENTS UNDERGOING INFERTILITY TREATMENT ACHIEVED LIVE BIRTHS. HOWEVER, THREE OF THESE FOUR PATIENTS HAD DELIVERY COMPLICATIONS SUCH AS ABNORMAL PLACENTATION AND SEVERE ABDOMINAL ADHESION. THERE WERE 5 CASES OF MISCARRIAGES IN 9 PREGNANT PATIENTS UNDERGOING INFERTILITY TREATMENT, AND 3 CASES IN 11 PREGNANT PATIENTS NOT UNDERGOING INFERTILITY TREATMENT. THE DIFFERENCE OF HISTORY OF PREVIOUS UTERINE SURGERY WAS NOT SIGNIFICANT (P = 0.161). MEDIAN TIME TO CONCEPTION WAS 184 DAYS (RANGE 101-948 DAYS) AND 330 DAYS (RANGE 95-925 DAYS) FOR THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT, RESPECTIVELY. DISCUSSION: THESE STUDIES ALSO DEMONSTRATED THE RELATIVELY HIGHER LIVE BIRTH RATE THAN THE CURRENT STUDY, ALTHOUGH, WE INCLUDED TEN PATIENTS UNDERGOING INFERTILITY TREATMENT, WHO UNDERWENT MULTIPLE ABORTIONS IN THE COURSE OF THEIR INFERTILITY TREATMENT. IN FACT, THERE IS LITTLE INFORMATION NOT ONLY ABOUT FUTURE PREGNANCY BUT ALSO ABOUT DELIVERY COMPLICATIONS IN PATIENTS UNDERGOING INFERTILITY TREATMENT. WE DEMONSTRATED A 20% OVARIAN DYSFUNCTION RATE, A 60% PREGNANCY RATE AND A 40% LIVE BIRTH RATE IN PATIENTS UNDERGOING INFERTILITY TREATMENT, A 55.6% MISCARRIAGE RATE, AND A 75% DELIVERY COMPLICATION RATE, WHICH COULD BE SIGNIFICANT INFORMATION FOR PATIENTS UNDERGOING INFERTILITY TREATMENT. INOUE ET AL. REPORTED THE RATES OF MISCARRIAGE AND DELIVERY COMPLICATIONS INCLUDING PLACENTA ACCRETA AND POSTPARTUM HEMORRHAGE TO BE 21.4% AND 40.0%, RESPECTIVELY. THESE WERE LOWER THAN IN THE CURRENT STUDY. THE CURRENT STUDY INCLUDES LOW NUMBER OF PATIENTS, HOWEVER, PATIENTS UNDERGOING INFERTILITY TREATMENT COULD BE AT A HIGHER RISK OF DELIVERY COMPLICATIONS. MOREOVER, IT WAS INDICATED THAT UAE ITSELF COULD BE THE FACTOR OF A DELIVERY COMPLICATION BECAUSE OF NO SIGNIFICANT DEFERENCE IN HISTORY OF PREVIOUS SURGERY, MASSIVE HEMORRHAGE AND ANGIOGRAPHIC ENDPOINT IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT. THEREFORE, THE RESULTS OF THE PREGNANCY RATE OF 60.9% AND LIVE BIRTH RATE OF 43.5%, INCLUDING PATIENTS UNDERGOING INFERTILITY TREATMENT, WERE ACCEPTABLE, CONSIDERING 62-100% OF PREGNANCY RATE AND 20% OF MISCARRIAGE RATE BY THE PAST RESEARCHES. THERE WAS A SIGNIFICANT DIFFERENCE IN THE OCCURRENCE OF UTERINE INFECTION AFTER UAE FOR MASSIVE HEMORRHAGE (P = 0.014). MULTIPLE FACTORS WERE CONSIDERED AS THE CAUSE OF THE RESULTS. REQUIRING MORE EMBOLIC MATERIALS SUCH AS A GELATIN SPONGE TO ACHIEVE EQUIVALENT ANGIOGRAPHIC ENDPOINTS AND CHANGES IN THE ENDOMETRIAL ENVIRONMENT UNDER MASSIVE HEMORRHAGE DUE TO A VASOSPASM, OFTEN EXPERIENCED DURING AN EMERGENT UAE FOR HEMODYNAMICALLY UNSTABLE PATIENTS, RESULTED IN ENDOMETRIAL ISCHEMIA. THE INCREASED USE OF A GELATIN SPONGE, CONVENTIONALLY USED FOR UAE IN POSTPARTUM OR POSTABORTION HEMORRHAGE, MAY CAUSE INFLAMMATORY REACTIONS, WHICH IN TURN CAUSE INFLAMMATION AROUND THE OCCLUDED ARTERIES, AND COULD BE RESPONSIBLE FOR UTERINE INFECTION AND SYNECHIA RESULTING IN FUTURE MISCARRIAGES OR ABNORMAL PLACENTATION. IN GENERAL, GELATIN SPONGE WAS MAINLY USED, HOWEVER, OTHER EMBOLIC MATERIALS SHOULD BE SELECTED DEPENDING ON HEMODYNAMICAL CONDITION OR TARGET ARTERY. REGARDING ANGIOGRAPHIC ENDPOINTS, WE COULD NOT DEMONSTRATE A REDUCTION IN COMPLICATIONS BY ADJUSTING ANGIOGRAPHIC ENDPOINTS. HOWEVER, IT SUGGESTS THE VALIDITY TO FIRMLY EMBOLIZE INTRAUTERINE BRANCHES OF UAS, EVEN IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT, CONSIDERING THAT THERE WAS NO SIGNIFICANT DIFFERENCE IN INCREASE OF UA SCORE AND OCCURRENCE OF UTERINE INFECTION AND ALL UA SCORES IN UAE FAILURE CASES WERE SCORE 0. THE LIMITATIONS OF THE CURRENT STUDY ARE THAT THIS STUDY IS RETROSPECTIVE AND INCLUDED A SMALL NUMBER OF CASES BECAUSE OF MISSING DETAILED ANGIOGRAPHIC DATA. MOREOVER, THE DIFFERENCES IN THE PATIENT'S BACKGROUND DISEASES AND THOSE BETWEEN THE OPERATORS OF THE UAE WERE NOT CONSIDERED, AND FOLLOW-UP OF ONLY POSTOPERATIVE COMPLICATIONS AND PREGNANCY OUTCOMES COULD BE INSUFFICIENT. IN CONCLUSION, IT WAS UNNECESSARY TO MODIFY ANGIOGRAPHIC ENDPOINT FOR EACH PATIENT ACCORDING TO THE SERIOUSNESS OF THE HEMORRHAGE AND SUGGESTING THE VALIDITY TO FIRMLY EMBOLIZE AN INTRAUTERINE BRANCH OF UA, EVEN IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT. THE PREGNANCY RATE AND LIVE BIRTH RATE WERE ACCEPTABLE. HOWEVER, THERE COULD BE A HIGHER RATE OF MISCARRIAGES AND DELIVERY COMPLICATIONS IN THESE PATIENTS. PFIZER IS A MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN IN THE COUNTRY OF INCIDENCE OR THE COUNTRY WHERE THE PRODUCT WAS PURCHASED (IF DIFFERENT). THIS MAY BE A DUPLICATE REPORT IF ANOTHER MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN HAS SUBMITTED THE SAME REPORT TO THE REGULATORY AUTHORITIES. FOLLOW-UP (22MAY2020): THIS IS A FOLLOW-UP REPORT BASED ON THE INFORMATION FROM THE PRODUCT QUALITY COMPLAINTS GROUP. THE PRODUCT DESCRIPTION WAS FOR GELFOAM STERILE SPONGE SIZE 100 X 1. DEVICE MALFUNCTION WAS REASONABLY SUGGESTED. THE SEVERITY OF HARM RANKING WAS A S4. THE FOLLOWING WAS THE DESCRIPTION OF COMPLAINT: PRODUCT COMPLAINT EXCHANGE: [PRODUCT COMPLAINT EXCHANGE: [AERS#: (B)(4); SUSPECT: ABSORBABLE GELATIN; EVENT: 10 CASES OF UTERINE INFECTIONS (16.2%)] [AERS#: (B)(4); SUSPECT: ABSORBABLE GELATIN; EVENT: 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED]. THE FOLLOWING WAS THE ROOT CAUSE ANALYSIS: PFIZER QUALITY OPERATIONS COULD NOT DETERMINE A ROOT CAUSE FOR THE REPORTED DEFECT TO BE RELATED TO THE SITE PRODUCTION PROCESS. A REVIEW OF PREVIOUSLY COMPLETED INVESTIGATION REPORTS DETERMINED TO BE WITHIN SCOPE DID NOT RESULT IN IDENTIFICATION OF A BATCH NUMBER, OR A ROOT CAUSE FOR THE REPORTED COMPLAINT. EXAMINATION OF A RETURNED COMPLAINT SAMPLE MAY HAVE AIDED IN IDENTIFICATION OF A ROOT CAUSE; HOWEVER, NONE WERE RECEIVED. IT IS UNKNOWN HOW THE REPORTED COMPLAINT SAMPLE WAS HANDLED, STORED, OR USED AFTER LEAVING THE PFIZER SITE. THE FOLLOWING WAS THE CONCLUSION: THE REVIEW OF ALL RECORDS AND REPORTS WITHIN SCOPE OF THIS INVESTIGATION DEMONSTRATED THE ACCEPTABILITY OF THE PRODUCT OVER THE TIMEFRAME WITHIN SCOPE. THE COMPLAINT HAS BEEN ESCALATED TO SAFETY FOR EVALUATION OF REGULATORY REPORTABILITY. FURTHER ACTION BY PFIZER MANUFACTURING SITE IS NOT REQUIRED. NO FOLLOW-UP ATTEMPTS ARE NEEDED. NO FURTHER INFORMATION IS EXPECTED. COMPANY CLINICAL EVALUATION COMMENT: THE USE OF ABSORBABLE GELATIN (GELFOAM) FOR UTERINE ARTERY EMBOLIZATION (UAE) FOR POSTPARTUM AND POSTABORTION HEMORRHAGE WAS CONSIDERED AS OFF LABEL USE, AND THE REPORTED EVENT UTERINE INFECTION WAS ASSOCIATED WITH THE OFF LABEL USE. THE UTERINE INFECTION RATE WAS 16.2% (10 OVER 59 PATIENTS) PER THIS LITERATURE STUDY REPORT. THERE WERE MULTIPLE FACTORS THAT MAY INFLUENCE UAE COMPLICATIONS, ESPECIALLY THE DEPTH OF UA AND THE DEGREE OF EMBOLIZATION FOR SECURING HEMOSTASIS. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE., COMMENT: THE USE OF ABSORBABLE GELATIN (GELFOAM) FOR UTERINE ARTERY EMBOLIZATION (UAE) FOR POSTPARTUM AND POSTABORTION HEMORRHAGE WAS CONSIDERED AS OFF LABEL USE, AND THE REPORTED EVENT OVARIAN DYSFUNCTION WAS ASSOCIATED WITH THE OFF LABEL USE OF GELFOAM. THE OVARIAN DYSFUNCTION RATE WAS 4.5% PER THIS LITERATURE STUDY REPORT. THERE WERE MULTIPLE FACTORS THAT MAY INFLUENCE UAE COMPLICATIONS, SUCH AS THE DEPTH OF UA AND THE DEGREE OF EMBOLIZATION FOR SECURING HEMOSTASIS. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.
OFF LABEL USE [OFF LABEL USE]. DRUG USE FOR UNAPPROVED INDICATION [PRODUCT USE IN UNAPPROVED INDICATION]. 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED [OVARIAN DISORDER]. CASE DESCRIPTION: THIS IS A LITERATURE REPORT FROM THE JAPANESE JOURNAL OF RADIOLOGY, 2020, VOL 38 (3); PP 240-247 DOI (10.1007/S11604-019-00907-2) ENTITLED UTERINE ARTERY EMBOLIZATION FOR POSTPARTUM AND POSTABORTION HEMORRHAGE: A RETROSPECTIVE ANALYSIS OF COMPLICATIONS, SUBSEQUENT FERTILITY AND PREGNANCY OUTCOMES. THIS AUTHOR REPORTED DIFFERENT EVENTS FOR TWELVE PATIENTS. THIS IS THE ELEVENTH OF TWELVE REPORTS. A FEMALE PATIENT OF AN UNSPECIFIED AGE STARTED TO RECEIVE GELATIN SPONGE (GS), VIA AN UNSPECIFIED ROUTE OF ADMINISTRATION BY PUMPING METHOD FROM AN UNSPECIFIED DATE AT UNKNOWN DOSE (INJECTION) FOR UTERINE ARTERY EMBOLIZATION (UAE) DUE TO POSTPARTUM OR POSTABORTION HEMORRHAGE. THE PATIENT'S MEDICAL HISTORY AND CONCOMITANT MEDICATIONS WERE NOT REPORTED. THE PATIENT EXPERIENCED OVARIAN DYSFUNCTION AFTER EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE. THE ACTION TAKEN IN RESPONSE TO THE EVENTS FOR ABSORBABLE GELATIN WAS UNKNOWN. THE PATIENT OUTCOME WAS UNKNOWN. WITH THESE BACKGROUNDS, WE INVESTIGATED FACTORS THAT INFLUENCE COMPLICATIONS AFTER UAE IN PATIENTS WITH REPRODUCTIVE DEMANDS, BASED ON PATIENT BACKGROUNDS AND ANGIOGRAPHIC ENDPOINTS. FURTHERMORE, WE STUDIED FUTURE PREGNANCY OUTCOMES, ESPECIALLY IN PATIENTS UNDERGOING INFERTILITY TREATMENT. MATERIALS AND METHODS: PATIENT PROFILES THIS RETROSPECTIVE STUDY WAS APPROVED BY THE INSTITUTIONAL REVIEW BOARD OF BOTH INSTITUTIONS. INFORMED CONSENTS FOR UAE WERE OBTAINED FROM ALL PATIENTS. THE APPROVAL NUMBER WAS 1310. SUBJECTS INCLUDED IN THIS STUDY WERE 75 WOMEN FROM 79 CONSECUTIVE SESSIONS FROM TWO TERTIARY REFERRAL CENTERS FROM THE OKINAWA PREFECTURE, JAPAN. THESE WOMEN UNDERWENT UAE FOR POSTPARTUM OR POSTABORTION HEMORRHAGE BETWEEN 2008 AND 2017. CASES OF HEMORRHAGE DUE TO MALIGNANCY WAS EXCLUDED AND THE CASES WITHOUT DETAILED ANGIOGRAM IMAGES OR CLINICAL INFORMATION WERE ALSO EXCLUDED. FINALLY, 59 PATIENTS WHO UNDERWENT 62 SESSIONS OF UAE IN TOTAL WERE ELIGIBLE, WHICH INCLUDING PRIMARY POSTPARTUM HEMORRHAGE IN 19 SESSIONS, SECONDARY POSTPARTUM HEMORRHAGE IN 5 SESSIONS, POSTABORTION HEMORRHAGE IN 27 SESSIONS, CERVICAL PREGNANCY IN 11 SESSIONS. DATA ON PATIENT CHARACTERISTICS SUCH AS AGE, PREGNANCY HISTORIES, PAST ILLNESS INCLUDING UTERINE SURGERY SUCH AS CAESAREAN SECTION (C/S), D&C AND HYSTEROSCOPIC RESECTION, HISTORY OF INFERTILITY TREATMENT AND DESIRE OF CHILDBEARING, BACKGROUND DISEASES THAT RESULTED IN RECEIVING UAE, HISTORY OF MASSIVE HEMORRHAGE, AND PREOPERATIVE HEMOGLOBIN LEVEL WERE EXTRACTED FROM THE MEDICAL RECORDS OF THE TWO MEDICAL CENTERS. WE DEFINED MASSIVE HEMORRHAGE AS A STATE WITH A SHOCK INDEX OF MORE THAN 1.0, OR WITH EXTRAVASATION DEMONSTRATED BY CONTRAST-ENHANCED COMPUTED TOMOGRAPHY OR DEMONSTRATED ANGIOGRAPHICALLY DURING UAE. EMBOLIC MATERIALS, DEGREE OF EMBOLIZATION OF THE UTERINE ARTERY, AND VISUALIZATION OF UOA ON THE UTERINE ANGIOGRAPHY BEFORE EMBOLIZATION WERE EVALUATED AS ANGIOGRAPHIC ITEMS. COMBINATION TREATMENT, INCLUDING THE CASES PERFORMED D&C OR TRANSCERVICAL RESECTION AFTER UAE, WAS ALSO RECORDED. AS PRIMARY OUTCOMES, SUBSEQUENT PREGNANCY AND PREGNANCY COMPLICATIONS SUCH AS PLACENTA ACCRETA WERE CONSIDERED PRIMARY OUTCOMES. WITH REGARDS TO CASES OF PREGNANCY AND MISCARRIAGE, CUMULATIVE NUMBER OF CASES WAS ALSO DESCRIBED. AS SECONDARY OUTCOMES, ACUTE COMPLICATIONS OF UTERINE INFECTIONS AND OVARIAN DYSFUNCTION WERE EVALUATED. WE DEFINED UTERINE INFECTION AS A CONDITION WITH PROLONGED FEVER ACCOMPANIED BY LOWER ABDOMINAL PAIN, CHILLS, AND SHIVERING CURED BY ADMINISTRATION OF INTRAVENOUS ANTIBIOTICS. CASES THAT COULD BE RETROSPECTIVELY REGARDED AS POST-EMBOLIZATION SYNDROME, NON-INFECTION CONDITIONS PRESENTING AS TRANSIENT FEVER AND LOWER ABDOMINAL PAIN, WERE CAREFULLY EXCLUDED. OVARIAN DYSFUNCTION WAS BASED ON SERUM FOLLICULAR STIMULATING HORMONE (FSH) ELEVATION OF MORE THAN 40 MIU/ML ACCORDING TO THE DEFINITION GIVEN IN A PREVIOUS RANDOMIZEDCONTROLLED TRIAL ABOUT OVARIAN RESERVE AFTER UAE FOR PATIENTS WITH LEIOMYOMAS. IN ADDITION, RESUMPTION OF REGULAR MENSES WAS REGARDED AS NORMAL OVARIAN FUNCTION. THE DEGREE OF EMBOLIZATION OF THE UA WAS CLASSIFIED BY A SCORE FROM 0 TO 2 DEPENDING ON THE STASIS OF THE INTRAUTERINE BRANCH OF THE UA . SCORE 0 WAS DEFINED AS THE STATE IN WHICH EVEN A SMALL AMOUNT OF FLOW FROM THE INTRAUTERINE BRANCH OF THE BILATERAL UA REMAINED. SCORE 1 WAS DEFINED AS STASIS OF FLOW FROM THE INTRAUTERINE BRANCH ON UNILATERAL SIDE. SCORE 2 WAS DEFINED AS STASIS ON BOTH SIDES OF THE INTRAUTERINE BRANCHES, AND FLOW MAINTAINED FROM A HORIZONTAL OR ASCENDING SEGMENT OF THE UAS. IN ADDITION, VISUALIZATION OF THE UOA BEFORE EMBOLIZATION WAS ALSO EVALUATED. IVR PROCEDURE IN ALMOST CASES, A 5-F SHEATH (MEDIKIT, TOKYO, JAPAN) WAS GENERALLY INSERTED FROM THE UNILATERAL FEMORAL ARTERY THROUGH WHICH A 5-F PIG TAIL CATHETER (FANSAC IV, TERUMO-CLINICAL SUPPLY, GIFU, JAPAN) WAS ADVANCED TO ABDOMINAL AORTA PRIOR TO SELECT UA. PELVIC AORTOGRAPHY WAS PERFORMED TO ENSURE ARTERIAL ANATOMY, ESPECIALLY THE INVOLVEMENT OF NON-UA WAS CAREFULLY EVALUATED. AFTER SELECTIVE CATHETERIZATION OF EACH UA USING A 5FR COBRA SHAPED CATHETER WITH A GUIDE WIRE (0.035, ANGLE TYPE; RADIFOCUS, TERUMO, TOKYO, JAPAN) AND A STANDARD COAXIAL 2.8F-MICROCATHETER SYSTEM (RENEGADE, BOSTON SCIENTIFIC CORP.), EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE BY PUMPING METHOD. AFTER BILATERAL UA EMBOLIZATION, OBSTETRICIAN EXAMINED AND CONFIRMED HEMOSTASIS CLINICALLY. IF ACTIVE BLEEDING PERSISTS, THE OTHER FEEDING ARTERY WAS DETECTED AND EMBOLIZED. STATISTICAL ANALYSIS: WE DIVIDED THE 62 CASES INTO TWO GROUPS BASED ON THE PRESENCE OF MASSIVE HEMORRHAGE AND 23 PATIENTS WHO HAD A DESIRE FOR CHILDBEARING WERE ALSO DIVIDED ACCORDING TO WHETHER THEY WERE UNDERGOING INFERTILITY TREATMENT OR NOT. R SOFTWARE (VERSION 3.4.1; R FOUNDATION FOR STATISTICAL COMPUTING, VIENNA, AUSTRIA) WAS USED FOR ALL STATISTICAL ANALYSES. CONTINUOUS VARIABLES ARE EXPRESSED AS THE MEAN +/- SD, AND CATEGORICAL VALUES ARE EXPRESSED AS NUMBERS AND FREQUENCIES. COMPARISON OF QUALITATIVE VARIABLES IN THE TWO GROUPS WAS PERFORMED USING FISHER'S EXACT TEST OR THE CHISQUARE TEST FOR INDEPENDENCE. COMPARISONS OF QUANTITATIVE VARIABLES IN THE TWO GROUPS WERE PERFORMED USING STUDENT'S T TEST. THE UA SCORES WERE COMPARED BETWEEN THE TWO GROUPS USING THE MANN-WHITNEY U TEST. THE COMPARISON OF UA SCORES WITH THE OCCURRENCE OF UTERINE INFECTION WAS ALSO ANALYZED USING THE MANN-WHITNEY U TEST. A P VALUE OF < 0.05 (TWO-TAILED) WAS CONSIDERED STATISTICALLY SIGNIFICANT. RESULTS THE MEAN AGE WAS 34.1 +/- 6.5 YEARS. MOST OF CASES (49 CASES, 79.0%) HAD HISTORIES OF PREVIOUS UTERINE SURGERY SUCH AS C/S AND D&C. THE CAUSES OF BLEEDING INCLUDED PRIMARY POSTPARTUM HEMORRHAGE IN 19 CASES (25.8%), SECONDARY POSTPARTUM HEMORRHAGE IN 5 CASES (8.1%), POSTABORTION HEMORRHAGE IN 27 CASES (43.5%), CERVICAL PREGNANCY IN 11 CASES (17.7%). TEN OF THE 23 PATIENTS (43.5%) WITH A DESIRE OF CHILDBEARING UNDERWENT INFERTILITY TREATMENT. THERE WERE 27 CASES (43.5%) OF MASSIVE HEMORRHAGE. GELATIN SPONGE BY PUMPING METHOD WAS MAINLY USED AS THE EMBOLIC MATERIAL. IN ONE CASE WITH MASSIVE HEMORRHAGE, 20% NBCA WAS USED FOR RIGHT UA TO PREVENT EARLY RE-CANALIZATION, FOLLOWING BY GELATIN SPONGE INJECTION. IN ONE CASE OF RETAINED PRODUCTS OF PLACENTA (RPOC) COMBINED WITH ARTERIOVENOUS MALFORMATION, AN ABSOLUTE ETHANOL WAS USED TO ERADICATE NIDUS AND VENOUS SAC. BILATERAL UA WAS EMBOLIZED BY 0.5 ML ABSOLUTE ETHANOL FOR EACH INJECTION IN TOTAL 9 ML, FOLLOWED BY PUSHABLE METALLIC COIL EMBOLIZATION. IN TWO CASES OF VAGINAL LACERATIONS, MIDDLE COLIC ARTERY OR INTERNAL PUDENDAL ARTERY WAS ALSO EMBOLIZED IN EACH CASE, RESPECTIVELY. THE CLINICAL SUCCESS RATE OF UAE COMBINED WITH HYSTEROSCOPIC RESECTION OR D&C WAS 95.2% (59/62 CASES). THREE PATIENTS OF THEM RECEIVED TWO UAES; TWO PATIENTS FOR RELAPSED HEMORRHAGE BY CERVICAL PREGNANCY AND RPOC, THE OTHER ONE FOR A PLACENTAL ACCRETA AFTER EIGHT YEARS FROM PREVIOUS UAE. REGARDING THE UA SCORE, 43 CASES HAD SCORE 0, 13 CASES HAD SCORE 1, AND 6 CASES HAD SCORE 2. UOA WAS VISUALIZED IN 15 CASES (24.2%). UA SCORE WAS 0 IN ALL TWO CASES OF RELAPSED HEMORRHAGE. AFTER UAE, 10 CASES OF UTERINE INFECTIONS (16.2%) AND 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED. TWO OF THE PATIENTS WITH UTERINE INFECTION RESULTED IN SUBSEQUENT HYSTERECTOMY AND ONE PATIENT RESULTED IN ASHERMAN'S SYNDROME. IN 10 CASE WITH UTERINE INFECTION, GELATIN SPONGE WAS USED IN ALL CASES AND METALLIC COIL IN 1 CASE. THE UA SCORES WERE AS FOLLOWS: SCORE 0 FOR 5 CASES, SCORE 1 FOR 4 CASES, SCORE 2 FOR 1 CASE. THERE WAS NO DIFFERENCE OF UA SCORE WHETHER AN OCCURRENCE OF UTERINE INFECTION OR NOT (P = 0.297). PREGNANCY OUTCOMES INCLUDED 20 CUMULATIVE PREGNANCIES IN 14 PATIENTS, 12 LIVE BIRTHS IN 10 PATIENTS, AND 8 CUMULATIVE MISCARRIAGES. PREGNANCY RATE AND LIVE BIRTH RATE WERE 60.9% (14 OF 23 PATIENTS) AND 43.5% (10 OF 23 PATIENTS) RESPECTIVELY. THE DELIVERY ROUTE OF THE 12 LIVE BIRTHS WAS NORMAL SPONTANEOUS VAGINAL DELIVERY IN 7 PATIENTS AND ELECTIVE C/S IN 5 PATIENTS. REGARDING COMPLICATIONS AT BIRTH, FOUR PATIENTS HAD PLACENTA ACCRETA, ONE OF WHOM HAD SEVERE PERITONEAL ADHESION DURING ELECTIVE C/S AND ANOTHER HAD ATONIC BLEEDING. THE OCCURRENCE OF UTERINE INFECTION WAS SIGNIFICANTLY HIGHER IN THE GROUP WITH MASSIVE HEMORRHAGE THAN THAT IN THE GROUP WITHOUT (P = 0.014) (TABLE 2). COMPARING THE ANGIOGRAPHIC ENDPOINTS BETWEEN THE TWO GROUPS, NEITHER THE DIFFERENCE IN THE UA SCORE (P = 0.109), NOR THE DIFFERENCE IN THE VISUALIZATION OF THE UOA (P = 0.111) WAS SIGNIFICANT. IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT, PATIENTS UNDERGOING INFERTILITY TREATMENT WERE OLDER (MEAN AGE 36.3 VS. 30.1 P = 0.012). FOUR OF THE NINE NULLIPAROUS PATIENTS UNDERGOING INFERTILITY TREATMENT ACHIEVED LIVE BIRTHS. HOWEVER, THREE OF THESE FOUR PATIENTS HAD DELIVERY COMPLICATIONS SUCH AS ABNORMAL PLACENTATION AND SEVERE ABDOMINAL ADHESION. THERE WERE 5 CASES OF MISCARRIAGES IN 9 PREGNANT PATIENTS UNDERGOING INFERTILITY TREATMENT, AND 3 CASES IN 11 PREGNANT PATIENTS NOT UNDERGOING INFERTILITY TREATMENT. THE DIFFERENCE OF HISTORY OF PREVIOUS UTERINE SURGERY WAS NOT SIGNIFICANT (P = 0.161). MEDIAN TIME TO CONCEPTION WAS 184 DAYS (RANGE 101-948 DAYS) AND 330 DAYS (RANGE 95-925 DAYS) FOR THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT, RESPECTIVELY. DISCUSSION: THESE STUDIES ALSO DEMONSTRATED THE RELATIVELY HIGHER LIVE BIRTH RATE THAN THE CURRENT STUDY, ALTHOUGH, WE INCLUDED TEN PATIENTS UNDERGOING INFERTILITY TREATMENT, WHO UNDERWENT MULTIPLE ABORTIONS IN THE COURSE OF THEIR INFERTILITY TREATMENT. IN FACT, THERE IS LITTLE INFORMATION NOT ONLY ABOUT FUTURE PREGNANCY BUT ALSO ABOUT DELIVERY COMPLICATIONS IN PATIENTS UNDERGOING INFERTILITY TREATMENT. WE DEMONSTRATED A 20% OVARIAN DYSFUNCTION RATE, A 60% PREGNANCY RATE AND A 40% LIVE BIRTH RATE IN PATIENTS UNDERGOING INFERTILITY TREATMENT, A 55.6% MISCARRIAGE RATE, AND A 75% DELIVERY COMPLICATION RATE, WHICH COULD BE SIGNIFICANT INFORMATION FOR PATIENTS UNDERGOING INFERTILITY TREATMENT. INOUE ET AL. REPORTED THE RATES OF MISCARRIAGE AND DELIVERY COMPLICATIONS INCLUDING PLACENTA ACCRETA AND POSTPARTUM HEMORRHAGE TO BE 21.4% AND 40.0%, RESPECTIVELY. THESE WERE LOWER THAN IN THE CURRENT STUDY. THE CURRENT STUDY INCLUDES LOW NUMBER OF PATIENTS, HOWEVER, PATIENTS UNDERGOING INFERTILITY TREATMENT COULD BE AT A HIGHER RISK OF DELIVERY COMPLICATIONS. MOREOVER, IT WAS INDICATED THAT UAE ITSELF COULD BE THE FACTOR OF A DELIVERY COMPLICATION BECAUSE OF NO SIGNIFICANT DEFERENCE IN HISTORY OF PREVIOUS SURGERY, MASSIVE HEMORRHAGE AND ANGIOGRAPHIC ENDPOINT IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT. THEREFORE, THE RESULTS OF THE PREGNANCY RATE OF 60.9% AND LIVE BIRTH RATE OF 43.5%, INCLUDING PATIENTS UNDERGOING INFERTILITY TREATMENT, WERE ACCEPTABLE, CONSIDERING 62-100% OF PREGNANCY RATE AND 20% OF MISCARRIAGE RATE BY THE PAST RESEARCHES. THERE WAS A SIGNIFICANT DIFFERENCE IN THE OCCURRENCE OF UTERINE INFECTION AFTER UAE FOR MASSIVE HEMORRHAGE (P = 0.014). MULTIPLE FACTORS WERE CONSIDERED AS THE CAUSE OF THE RESULTS. REQUIRING MORE EMBOLIC MATERIALS SUCH AS A GELATIN SPONGE TO ACHIEVE EQUIVALENT ANGIOGRAPHIC ENDPOINTS AND CHANGES IN THE ENDOMETRIAL ENVIRONMENT UNDER MASSIVE HEMORRHAGE DUE TO A VASOSPASM, OFTEN EXPERIENCED DURING AN EMERGENT UAE FOR HEMODYNAMICALLY UNSTABLE PATIENTS, RESULTED IN ENDOMETRIAL ISCHEMIA. THE INCREASED USE OF A GELATIN SPONGE, CONVENTIONALLY USED FOR UAE IN POSTPARTUM OR POSTABORTION HEMORRHAGE, MAY CAUSE INFLAMMATORY REACTIONS, WHICH IN TURN CAUSE INFLAMMATION AROUND THE OCCLUDED ARTERIES, AND COULD BE RESPONSIBLE FOR UTERINE INFECTION AND SYNECHIA RESULTING IN FUTURE MISCARRIAGES OR ABNORMAL PLACENTATION. IN GENERAL, GELATIN SPONGE WAS MAINLY USED, HOWEVER, OTHER EMBOLIC MATERIALS SHOULD BE SELECTED DEPENDING ON HEMODYNAMICAL CONDITION OR TARGET ARTERY. REGARDING ANGIOGRAPHIC ENDPOINTS, WE COULD NOT DEMONSTRATE A REDUCTION IN COMPLICATIONS BY ADJUSTING ANGIOGRAPHIC ENDPOINTS. HOWEVER, IT SUGGESTS THE VALIDITY TO FIRMLY EMBOLIZE INTRAUTERINE BRANCHES OF UAS, EVEN IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT, CONSIDERING THAT THERE WAS NO SIGNIFICANT DIFFERENCE IN INCREASE OF UA SCORE AND OCCURRENCE OF UTERINE INFECTION AND ALL UA SCORES IN UAE FAILURE CASES WERE SCORE 0. THE LIMITATIONS OF THE CURRENT STUDY ARE THAT THIS STUDY IS RETROSPECTIVE AND INCLUDED A SMALL NUMBER OF CASES BECAUSE OF MISSING DETAILED ANGIOGRAPHIC DATA. MOREOVER, THE DIFFERENCES IN THE PATIENTS BACKGROUND DISEASES AND THOSE BETWEEN THE OPERATORS OF THE UAE WERE NOT CONSIDERED, AND FOLLOW-UP OF ONLY POSTOPERATIVE COMPLICATIONS AND PREGNANCY OUTCOMES COULD BE INSUFFICIENT. IN CONCLUSION, IT WAS UNNECESSARY TO MODIFY ANGIOGRAPHIC ENDPOINT FOR EACH PATIENT ACCORDING TO THE SERIOUSNESS OF THE HEMORRHAGE AND SUGGESTING THE VALIDITY TO FIRMLY EMBOLIZE AN INTRAUTERINE BRANCH OF UA, EVEN IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT. THE PREGNANCY RATE AND LIVE BIRTH RATE WERE ACCEPTABLE. HOWEVER, THERE COULD BE A HIGHER RATE OF MISCARRIAGES AND DELIVERY COMPLICATIONS IN THESE PATIENTS. ADDITIONAL INFORMATION HAS BEEN REQUESTED AND WILL BE PROVIDED AS IT BECOMES AVAILABLE. PFIZER IS A MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN IN THE COUNTRY OF INCIDENCE OR THE COUNTRY WHERE THE PRODUCT WAS PURCHASED (IF DIFFERENT). THIS MAY BE A DUPLICATE REPORT IF ANOTHER MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN HAS SUBMITTED THE SAME REPORT TO THE REGULATORY AUTHORITIES. COMPANY CLINICAL EVALUATION COMMENT: THE USE OF ABSORBABLE GELATIN (GELFOAM) FOR UTERINE ARTERY EMBOLIZATION (UAE) FOR POSTPARTUM AND POSTABORTION HEMORRHAGE WAS CONSIDERED AS OFF LABEL USE, AND THE REPORTED EVENT OVARIAN DYSFUNCTION WAS ASSOCIATED WITH THE OFF LABEL USE OF GELFOAM. THE OVARIAN DYSFUNCTION RATE WAS 4.5% PER THIS LITERATURE STUDY REPORT. THERE WERE MULTIPLE FACTORS THAT MAY INFLUENCE UAE COMPLICATIONS, SUCH AS THE DEPTH OF UA AND THE DEGREE OF EMBOLIZATION FOR SECURING HEMOSTASIS. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.
EVENT VERBATIM [PREFERRED TERM] OFF LABEL USE [OFF LABEL USE] , DRUG USE FOR UNAPPROVED INDICATION [PRODUCT USE IN UNAPPROVED INDICATION] , 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED [OVARIAN DISORDER],.CASE NARRATIVE:THIS IS A LITERATURE REPORT FROM THE JAPANESE JOURNAL OF RADIOLOGY, 2020, VOL 38 (3); PP 240-247 DOI (10.1007/S11604-019-00907-2). ENTITLED UTERINE ARTERY EMBOLIZATION FOR POSTPARTUM AND POSTABORTION HEMORRHAGE: A RETROSPECTIVE ANALYSIS OF COMPLICATIONS, SUBSEQUENT FERTILITY AND PREGNANCY OUTCOMES. THIS AUTHOR REPORTED DIFFERENT EVENTS FOR TWELVE PATIENTS. THIS IS THE ELEVENTH OF TWELVE REPORTS. A FEMALE PATIENT OF AN UNSPECIFIED AGE STARTED TO RECEIVE GELATIN SPONGE (GS), VIA AN UNSPECIFIED ROUTE OF ADMINISTRATION BY PUMPING METHOD FROM AN UNSPECIFIED DATE AT UNKNOWN DOSE (INJECTION) FOR UTERINE ARTERY EMBOLIZATION (UAE) DUE TO POSTPARTUM OR POSTABORTION HEMORRHAGE. THE PATIENT'S MEDICAL HISTORY AND CONCOMITANT MEDICATIONS WERE NOT REPORTED. THE PATIENT EXPERIENCED OVARIAN DYSFUNCTION AFTER EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE. THE ACTION TAKEN IN RESPONSE TO THE EVENTS FOR ABSORBABLE GELATIN WAS UNKNOWN. THE PATIENT OUTCOME WAS UNKNOWN. WITH THESE BACKGROUNDS, WE INVESTIGATED FACTORS THAT INFLUENCE COMPLICATIONS AFTER UAE IN PATIENTS WITH REPRODUCTIVE DEMANDS, BASED ON PATIENT BACKGROUNDS AND ANGIOGRAPHIC ENDPOINTS. FURTHERMORE, WE STUDIED FUTURE PREGNANCY OUTCOMES, ESPECIALLY IN PATIENTS UNDERGOING INFERTILITY TREATMENT. MATERIALS AND METHODS: PATIENT PROFILES THIS RETROSPECTIVE STUDY WAS APPROVED BY THE INSTITUTIONAL REVIEW BOARD OF BOTH INSTITUTIONS. INFORMED CONSENTS FOR UAE WERE OBTAINED FROM ALL PATIENTS. THE APPROVAL NUMBER WAS (B)(4). SUBJECTS INCLUDED IN THIS STUDY WERE 75 WOMEN FROM 79 CONSECUTIVE SESSIONS FROM TWO TERTIARY REFERRAL CENTERS FROM THE (B)(4). THESE WOMEN UNDERWENT UAE FOR POSTPARTUM OR POSTABORTION HEMORRHAGE BETWEEN 2008 AND 2017. CASES OF HEMORRHAGE DUE TO MALIGNANCY WAS EXCLUDED AND THE CASES WITHOUT DETAILED ANGIOGRAM IMAGES OR CLINICAL INFORMATION WERE ALSO EXCLUDED. FINALLY, 59 PATIENTS WHO UNDERWENT 62 SESSIONS OF UAE IN TOTAL WERE ELIGIBLE, WHICH INCLUDING PRIMARY POSTPARTUM HEMORRHAGE IN 19 SESSIONS, SECONDARY POSTPARTUM HEMORRHAGE IN 5 SESSIONS, POSTABORTION HEMORRHAGE IN 27 SESSIONS, CERVICAL PREGNANCY IN 11 SESSIONS. DATA ON PATIENT CHARACTERISTICS SUCH AS AGE, PREGNANCY HISTORIES, PAST ILLNESS INCLUDING UTERINE SURGERY SUCH AS CAESAREAN SECTION (C/S), D&C AND HYSTEROSCOPIC RESECTION, HISTORY OF INFERTILITY TREATMENT AND DESIRE OF CHILDBEARING, BACKGROUND DISEASES THAT RESULTED IN RECEIVING UAE, HISTORY OF MASSIVE HEMORRHAGE, AND PREOPERATIVE HEMOGLOBIN LEVEL WERE EXTRACTED FROM THE MEDICAL RECORDS OF THE TWO MEDICAL CENTERS. WE DEFINED MASSIVE HEMORRHAGE AS A STATE WITH A SHOCK INDEX OF MORE THAN 1.0, OR WITH EXTRAVASATION DEMONSTRATED BY CONTRAST-ENHANCED COMPUTED TOMOGRAPHY OR DEMONSTRATED ANGIOGRAPHICALLY DURING UAE. EMBOLIC MATERIALS, DEGREE OF EMBOLIZATION OF THE UTERINE ARTERY, AND VISUALIZATION OF UOA ON THE UTERINE ANGIOGRAPHY BEFORE EMBOLIZATION WERE EVALUATED AS ANGIOGRAPHIC ITEMS. COMBINATION TREATMENT, INCLUDING THE CASES PERFORMED D&C OR TRANSCERVICAL RESECTION AFTER UAE, WAS ALSO RECORDED. AS PRIMARY OUTCOMES, SUBSEQUENT PREGNANCY AND PREGNANCY COMPLICATIONS SUCH AS PLACENTA ACCRETA WERE CONSIDERED PRIMARY OUTCOMES. WITH REGARDS TO CASES OF PREGNANCY AND MISCARRIAGE, CUMULATIVE NUMBER OF CASES WAS ALSO DESCRIBED. AS SECONDARY OUTCOMES, ACUTE COMPLICATIONS OF UTERINE INFECTIONS AND OVARIAN DYSFUNCTION WERE EVALUATED. WE DEFINED UTERINE INFECTION AS A CONDITION WITH PROLONGED FEVER ACCOMPANIED BY LOWER ABDOMINAL PAIN, CHILLS, AND SHIVERING CURED BY ADMINISTRATION OF INTRAVENOUS ANTIBIOTICS. CASES THAT COULD BE RETROSPECTIVELY REGARDED AS POST-EMBOLIZATION SYNDROME, NON-INFECTION CONDITIONS PRESENTING AS TRANSIENT FEVER AND LOWER ABDOMINAL PAIN, WERE CAREFULLY EXCLUDED. OVARIAN DYSFUNCTION WAS BASED ON SERUM FOLLICULAR STIMULATING HORMONE (FSH) ELEVATION OF MORE THAN 40 MIU/ML ACCORDING TO THE DEFINITION GIVEN IN A PREVIOUS RANDOMIZED CONTROLLED TRIAL ABOUT OVARIAN RESERVE AFTER UAE FOR PATIENTS WITH LEIOMYOMAS. IN ADDITION, RESUMPTION OF REGULAR MENSES WAS REGARDED AS NORMAL OVARIAN FUNCTION. THE DEGREE OF EMBOLIZATION OF THE UA WAS CLASSIFIED BY A SCORE FROM 0 TO 2 DEPENDING ON THE STASIS OF THE INTRAUTERINE BRANCH OF THE UA . SCORE 0 WAS DEFINED AS THE STATE IN WHICH EVEN A SMALL AMOUNT OF FLOW FROM THE INTRAUTERINE BRANCH OF THE BILATERAL UA REMAINED. SCORE 1 WAS DEFINED AS STASIS OF FLOW FROM THE INTRAUTERINE BRANCH ON UNILATERAL SIDE. SCORE 2 WAS DEFINED AS STASIS ON BOTH SIDES OF THE INTRAUTERINE BRANCHES, AND FLOW MAINTAINED FROM A HORIZONTAL OR ASCENDING SEGMENT OF THE UAS. IN ADDITION, VISUALIZATION OF THE UOA BEFORE EMBOLIZATION WAS ALSO EVALUATED. IVR PROCEDURE IN ALMOST CASES, A 5-F SHEATH (MEDIKIT, TOKYO, JAPAN) WAS GENERALLY INSERTED FROM THE UNILATERAL FEMORAL ARTERY THROUGH WHICH A 5-F PIG TAIL CATHETER (FANSAC IV, TERUMO-CLINICAL SUPPLY, GIFU, JAPAN) WAS ADVANCED TO ABDOMINAL AORTA PRIOR TO SELECT UA. PELVIC AORTOGRAPHY WAS PERFORMED TO ENSURE ARTERIAL ANATOMY, ESPECIALLY THE INVOLVEMENT OF NON-UA WAS CAREFULLY EVALUATED. AFTER SELECTIVE CATHETERIZATION OF EACH UA USING A 5FR COBRA SHAPED CATHETER WITH A GUIDE WIRE (0.035, ANGLE TYPE; RADIFOCUS, TERUMO, TOKYO, JAPAN) AND A STANDARD COAXIAL 2.8F-MICROCATHETER SYSTEM (RENEGADE, BOSTON SCIENTIFIC CORP.), EMBOLIZATION WAS PERFORMED WITH GELATIN SPONGE BY PUMPING METHOD. AFTER BILATERAL UA EMBOLIZATION, OBSTETRICIAN EXAMINED AND CONFIRMED HEMOSTASIS CLINICALLY. IF ACTIVE BLEEDING PERSISTS, THE OTHER FEEDING ARTERY WAS DETECTED AND EMBOLIZED. STATISTICAL ANALYSIS: WE DIVIDED THE 62 CASES INTO TWO GROUPS BASED ON THE PRESENCE OF MASSIVE HEMORRHAGE AND 23 PATIENTS WHO HAD A DESIRE FOR CHILDBEARING WERE ALSO DIVIDED ACCORDING TO WHETHER THEY WERE UNDERGOING INFERTILITY TREATMENT OR NOT. R SOFTWARE (VERSION 3.4.1; R FOUNDATION FOR STATISTICAL COMPUTING, VIENNA, AUSTRIA) WAS USED FOR ALL STATISTICAL ANALYSES. CONTINUOUS VARIABLES ARE EXPRESSED AS THE MEAN +/- SD, AND CATEGORICAL VALUES ARE EXPRESSED AS NUMBERS AND FREQUENCIES. COMPARISON OF QUALITATIVE VARIABLES IN THE TWO GROUPS WAS PERFORMED USING FISHER'S EXACT TEST OR THE CHISQUARE TEST FOR INDEPENDENCE. COMPARISONS OF QUANTITATIVE VARIABLES IN THE TWO GROUPS WERE PERFORMED USING STUDENT'S T TEST. THE UA SCORES WERE COMPARED BETWEEN THE TWO GROUPS USING THE MANN-WHITNEY U TEST. THE COMPARISON OF UA SCORES WITH THE OCCURRENCE OF UTERINE INFECTION WAS ALSO ANALYZED USING THE MANN-WHITNEY U TEST. A P VALUE OF < 0.05 (TWO-TAILED) WAS CONSIDERED STATISTICALLY SIGNIFICANT. RESULTS THE MEAN AGE WAS 34.1 +/- 6.5 YEARS. MOST OF CASES (49 CASES, 79.0%) HAD HISTORIES OF PREVIOUS UTERINE SURGERY SUCH AS C/S AND D&C. THE CAUSES OF BLEEDING INCLUDED PRIMARY POSTPARTUM HEMORRHAGE IN 19 CASES (25.8%), SECONDARY POSTPARTUM HEMORRHAGE IN 5 CASES (8.1%), POSTABORTION HEMORRHAGE IN 27 CASES (43.5%), CERVICAL PREGNANCY IN 11 CASES (17.7%). TEN OF THE 23 PATIENTS (43.5%) WITH A DESIRE OF CHILDBEARING UNDERWENT INFERTILITY TREATMENT. THERE WERE 27 CASES (43.5%) OF MASSIVE HEMORRHAGE. GELATIN SPONGE BY PUMPING METHOD WAS MAINLY USED AS THE EMBOLIC MATERIAL. IN ONE CASE WITH MASSIVE HEMORRHAGE, 20% NBCA WAS USED FOR RIGHT UA TO PREVENT EARLY RE-CANALIZATION, FOLLOWING BY GELATIN SPONGE INJECTION. IN ONE CASE OF RETAINED PRODUCTS OF PLACENTA (RPOC) COMBINED WITH ARTERIOVENOUS MALFORMATION, AN ABSOLUTE ETHANOL WAS USED TO ERADICATE NIDUS AND VENOUS SAC. BILATERAL UA WAS EMBOLIZED BY 0.5 ML ABSOLUTE ETHANOL FOR EACH INJECTION IN TOTAL 9 ML, FOLLOWED BY PUSHABLE METALLIC COIL EMBOLIZATION. IN TWO CASES OF VAGINAL LACERATIONS, MIDDLE COLIC ARTERY OR INTERNAL PUDENDAL ARTERY WAS ALSO EMBOLIZED IN EACH CASE, RESPECTIVELY. THE CLINICAL SUCCESS RATE OF UAE COMBINED WITH HYSTEROSCOPIC RESECTION OR D&C WAS 95.2% (59/62 CASES). THREE PATIENTS OF THEM RECEIVED TWO UAES; TWO PATIENTS FOR RELAPSED HEMORRHAGE BY CERVICAL PREGNANCY AND RPOC, THE OTHER ONE FOR A PLACENTAL ACCRETA AFTER EIGHT YEARS FROM PREVIOUS UAE. REGARDING THE UA SCORE, 43 CASES HAD SCORE 0, 13 CASES HAD SCORE 1, AND 6 CASES HAD SCORE 2. UOA WAS VISUALIZED IN 15 CASES (24.2%). UA SCORE WAS 0 IN ALL TWO CASES OF RELAPSED HEMORRHAGE. AFTER UAE, 10 CASES OF UTERINE INFECTIONS (16.2%) AND 2 CASES OF OVARIAN DYSFUNCTIONS (4.9%) OCCURRED. TWO OF THE PATIENTS WITH UTERINE INFECTION RESULTED IN SUBSEQUENT HYSTERECTOMY AND ONE PATIENT RESULTED IN ASHERMAN'S SYNDROME. IN 10 CASE WITH UTERINE INFECTION, GELATIN SPONGE WAS USED IN ALL CASES AND METALLIC COIL IN 1 CASE. THE UA SCORES WERE AS FOLLOWS: SCORE 0 FOR 5 CASES, SCORE 1 FOR 4 CASES, SCORE 2 FOR 1 CASE. THERE WAS NO DIFFERENCE OF UA SCORE WHETHER AN OCCURRENCE OF UTERINE INFECTION OR NOT (P = 0.297). PREGNANCY OUTCOMES INCLUDED 20 CUMULATIVE PREGNANCIES IN 14 PATIENTS, 12 LIVE BIRTHS IN 10 PATIENTS, AND 8 CUMULATIVE MISCARRIAGES. PREGNANCY RATE AND LIVE BIRTH RATE WERE 60.9% (14 OF 23 PATIENTS) AND 43.5% (10 OF 23 PATIENTS) RESPECTIVELY. THE DELIVERY ROUTE OF THE 12 LIVE BIRTHS WAS NORMAL SPONTANEOUS VAGINAL DELIVERY IN 7 PATIENTS AND ELECTIVE C/S IN 5 PATIENTS. REGARDING COMPLICATIONS AT BIRTH, FOUR PATIENTS HAD PLACENTA ACCRETA, ONE OF WHOM HAD SEVERE PERITONEAL ADHESION DURING ELECTIVE C/S AND ANOTHER HAD ATONIC BLEEDING. THE OCCURRENCE OF UTERINE INFECTION WAS SIGNIFICANTLY HIGHER IN THE GROUP WITH MASSIVE HEMORRHAGE THAN THAT IN THE GROUP WITHOUT (P = 0.014) (TABLE 2). COMPARING THE ANGIOGRAPHIC ENDPOINTS BETWEEN THE TWO GROUPS, NEITHER THE DIFFERENCE IN THE UA SCORE (P = 0.109), NOR THE DIFFERENCE IN THE VISUALIZATION OF THE UOA (P = 0.111) WAS SIGNIFICANT. IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT, PATIENTS UNDERGOING INFERTILITY TREATMENT WERE OLDER (MEAN AGE 36.3 VS. 30.1 P = 0.012). FOUR OF THE NINE NULLIPAROUS PATIENTS UNDERGOING INFERTILITY TREATMENT ACHIEVED LIVE BIRTHS. HOWEVER, THREE OF THESE FOUR PATIENTS HAD DELIVERY COMPLICATIONS SUCH AS ABNORMAL PLACENTATION AND SEVERE ABDOMINAL ADHESION. THERE WERE 5 CASES OF MISCARRIAGES IN 9 PREGNANT PATIENTS UNDERGOING INFERTILITY TREATMENT, AND 3 CASES IN 11 PREGNANT PATIENTS NOT UNDERGOING INFERTILITY TREATMENT. THE DIFFERENCE OF HISTORY OF PREVIOUS UTERINE SURGERY WAS NOT SIGNIFICANT (P = 0.161). MEDIAN TIME TO CONCEPTION WAS 184 DAYS (RANGE 101-948 DAYS) AND 330 DAYS (RANGE 95-925 DAYS) FOR THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT, RESPECTIVELY. DISCUSSION: THESE STUDIES ALSO DEMONSTRATED THE RELATIVELY HIGHER LIVE BIRTH RATE THAN THE CURRENT STUDY, ALTHOUGH, WE INCLUDED TEN PATIENTS UNDERGOING INFERTILITY TREATMENT, WHO UNDERWENT MULTIPLE ABORTIONS IN THE COURSE OF THEIR INFERTILITY TREATMENT. IN FACT, THERE IS LITTLE INFORMATION NOT ONLY ABOUT FUTURE PREGNANCY BUT ALSO ABOUT DELIVERY COMPLICATIONS IN PATIENTS UNDERGOING INFERTILITY TREATMENT. WE DEMONSTRATED A 20% OVARIAN DYSFUNCTION RATE, A 60% PREGNANCY RATE AND A 40% LIVE BIRTH RATE IN PATIENTS UNDERGOING INFERTILITY TREATMENT, A 55.6% MISCARRIAGE RATE, AND A 75% DELIVERY COMPLICATION RATE, WHICH COULD BE SIGNIFICANT INFORMATION FOR PATIENTS UNDERGOING INFERTILITY TREATMENT. INOUE ET AL. REPORTED THE RATES OF MISCARRIAGE AND DELIVERY COMPLICATIONS INCLUDING PLACENTA ACCRETA AND POSTPARTUM HEMORRHAGE TO BE 21.4% AND 40.0%, RESPECTIVELY. THESE WERE LOWER THAN IN THE CURRENT STUDY. THE CURRENT STUDY INCLUDES LOW NUMBER OF PATIENTS, HOWEVER, PATIENTS UNDERGOING INFERTILITY TREATMENT COULD BE AT A HIGHER RISK OF DELIVERY COMPLICATIONS. MOREOVER, IT WAS INDICATED THAT UAE ITSELF COULD BE THE FACTOR OF A DELIVERY COMPLICATION BECAUSE OF NO SIGNIFICANT DEFERENCE IN HISTORY OF PREVIOUS SURGERY, MASSIVE HEMORRHAGE AND ANGIOGRAPHIC ENDPOINT IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT OR NOT. THEREFORE, THE RESULTS OF THE PREGNANCY RATE OF 60.9% AND LIVE BIRTH RATE OF 43.5%, INCLUDING PATIENTS UNDERGOING INFERTILITY TREATMENT, WERE ACCEPTABLE, CONSIDERING 62-100% OF PREGNANCY RATE AND 20% OF MISCARRIAGE RATE BY THE PAST RESEARCHES. THERE WAS A SIGNIFICANT DIFFERENCE IN THE OCCURRENCE OF UTERINE INFECTION AFTER UAE FOR MASSIVE HEMORRHAGE (P = 0.014). MULTIPLE FACTORS WERE CONSIDERED AS THE CAUSE OF THE RESULTS. REQUIRING MORE EMBOLIC MATERIALS SUCH AS A GELATIN SPONGE TO ACHIEVE EQUIVALENT ANGIOGRAPHIC ENDPOINTS AND CHANGES IN THE ENDOMETRIAL ENVIRONMENT UNDER MASSIVE HEMORRHAGE DUE TO A VASOSPASM, OFTEN EXPERIENCED DURING AN EMERGENT UAE FOR HEMODYNAMICALLY UNSTABLE PATIENTS, RESULTED IN ENDOMETRIAL ISCHEMIA. THE INCREASED USE OF A GELATIN SPONGE, CONVENTIONALLY USED FOR UAE IN POSTPARTUM OR POSTABORTION HEMORRHAGE, MAY CAUSE INFLAMMATORY REACTIONS, WHICH IN TURN CAUSE INFLAMMATION AROUND THE OCCLUDED ARTERIES, AND COULD BE RESPONSIBLE FOR UTERINE INFECTION AND SYNECHIA RESULTING IN FUTURE MISCARRIAGES OR ABNORMAL PLACENTATION. IN GENERAL, GELATIN SPONGE WAS MAINLY USED, HOWEVER, OTHER EMBOLIC MATERIALS SHOULD BE SELECTED DEPENDING ON HEMODYNAMICAL CONDITION OR TARGET ARTERY. REGARDING ANGIOGRAPHIC ENDPOINTS, WE COULD NOT DEMONSTRATE A REDUCTION IN COMPLICATIONS BY ADJUSTING ANGIOGRAPHIC ENDPOINTS. HOWEVER, IT SUGGESTS THE VALIDITY TO FIRMLY EMBOLIZE INTRAUTERINE BRANCHES OF UAS, EVEN IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT, CONSIDERING THAT THERE WAS NO SIGNIFICANT DIFFERENCE IN INCREASE OF UA SCORE AND OCCURRENCE OF UTERINE INFECTION AND ALL UA SCORES IN UAE FAILURE CASES WERE SCORE 0. THE LIMITATIONS OF THE CURRENT STUDY ARE THAT THIS STUDY IS RETROSPECTIVE AND INCLUDED A SMALL NUMBER OF CASES BECAUSE OF MISSING DETAILED ANGIOGRAPHIC DATA. MOREOVER, THE DIFFERENCES IN THE PATIENTS BACKGROUND DISEASES AND THOSE BETWEEN THE OPERATORS OF THE UAE WERE NOT CONSIDERED, AND FOLLOW-UP OF ONLY POSTOPERATIVE COMPLICATIONS AND PREGNANCY OUTCOMES COULD BE INSUFFICIENT. IN CONCLUSION, IT WAS UNNECESSARY TO MODIFY ANGIOGRAPHIC ENDPOINT FOR EACH PATIENT ACCORDING TO THE SERIOUSNESS OF THE HEMORRHAGE AND SUGGESTING THE VALIDITY TO FIRMLY EMBOLIZE AN INTRAUTERINE BRANCH OF UA, EVEN IN THE PATIENTS UNDERGOING INFERTILITY TREATMENT. THE PREGNANCY RATE AND LIVE BIRTH RATE WERE ACCEPTABLE. HOWEVER, THERE COULD BE A HIGHER RATE OF MISCARRIAGES AND DELIVERY COMPLICATIONS IN THESE PATIENTS. ADDITIONAL INFORMATION HAS BEEN REQUESTED AND WILL BE PROVIDED AS IT BECOMES AVAILABLE. PFIZER IS A MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN IN THE COUNTRY OF INCIDENCE OR THE COUNTRY WHERE THE PRODUCT WAS PURCHASED (IF DIFFERENT). THIS MAY BE A DUPLICATE REPORT IF ANOTHER MARKETING AUTHORIZATION HOLDER OF ABSORBABLE GELATIN HAS SUBMITTED THE SAME REPORT TO THE REGULATORY AUTHORITIES. COMPANY CLINICAL EVALUATION COMMENT: THE USE OF ABSORBABLE GELATIN (GELFOAM) FOR UTERINE ARTERY EMBOLIZATION (UAE) FOR POSTPARTUM AND POSTABORTION HEMORRHAGE WAS CONSIDERED AS OFF LABEL USE, AND THE REPORTED EVENT OVARIAN DYSFUNCTION WAS ASSOCIATED WITH THE OFF LABEL USE OF GELFOAM. THE OVARIAN DYSFUNCTION RATE WAS 4.5% PER THIS LITERATURE STUDY REPORT. THERE WERE MULTIPLE FACTORS THAT MAY INFLUENCE UAE COMPLICATIONS, SUCH AS THE DEPTH OF UA AND THE DEGREE OF EMBOLIZATION FOR SECURING HEMOSTASIS. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE., COMMENT: THE USE OF ABSORBABLE GELATIN (GELFOAM) FOR UTERINE ARTERY EMBOLIZATION (UAE) FOR POSTPARTUM AND POSTABORTION HEMORRHAGE WAS CONSIDERED AS OFF LABEL USE, AND THE REPORTED EVENT OVARIAN DYSFUNCTION WAS ASSOCIATED WITH THE OFF LABEL USE OF GELFOAM. THE OVARIAN DYSFUNCTION RATE WAS 4.5% PER THIS LITERATURE STUDY REPORT. THERE WERE MULTIPLE FACTORS THAT MAY INFLUENCE UAE COMPLICATIONS, SUCH AS THE DEPTH OF UA AND THE DEGREE OF EMBOLIZATION FOR SECURING HEMOSTASIS. THE IMPACT OF THIS REPORT ON THE BENEFIT/RISK PROFILE OF THE PFIZER PRODUCT IS EVALUATED AS PART OF PFIZER PROCEDURES FOR SAFETY EVALUATION, INCLUDING THE REVIEW AND ANALYSIS OF AGGREGATE DATA FOR ADVERSE EVENTS. ANY SAFETY CONCERN IDENTIFIED AS PART OF THIS REVIEW, AS WELL AS ANY APPROPRIATE ACTION IN RESPONSE, WILL BE PROMPTLY NOTIFIED TO REGULATORY AUTHORITIES, ETHICS COMMITTEES AND INVESTIGATORS, AS APPROPRIATE.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 411535 | ABSORBABLE GELATIN | SPONGE, STERILE; CLASS III | LMF | PFIZER, INC. (DEVICE) |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | Other| R |