Article 1: - Pregnancy possible after uterine artery embolization for leiomyomata (Fibroids)

Article 2: - UFE with PVA particles ultimately did not affect fertility in the women who underwent the procedure.

Article 3: - Pregnancy Following Uterine Artery Embolization with PVA Particles for Patients with Uterine Fibroid or Adenomyosis.

Article 4: - Pregnancy after fibroid treatment.

Article 5: - Pregnancy after uterine artery embolization for leiomyomata: A series of 56 completed pegnancies.

Article 1

http://www.oncolink.org/resources/article.cfm?c=3&s=8&ss=23&id=11411&month=12&year=2004

Pregnancy possible after uterine artery embolization for leiomyomata (Fibroids)
Megan Rauscher
Last Updated: 2004-12-29 9:47:19 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Women can conceive and carry a child to term following uterine artery embolization (UAE) for treatment of symptomatic uterine fibroids, new findings suggest. However, women who become pregnant after UAE should be closely monitored for abnormal placental development, investigators say.

Obstet Gynecol 2005;105:67-76.

Article 2

UFE with PVA particles ultimately did not affect fertility in the women who underwent the procedure.

http://www.springerlink.com/content/l610167407872702/

Man Deuk Kim1 , Nahk Keun Kim2, Hee Jin Kim1 and Mee Hwa Lee2

Published online: 12 August 2005
Abstract
Purpose:  To determine whether uterine fibroid embolization (UFE) with polyvinyl alcohol (PVA) particles affects fertility in women desiring future pregnancy.

Methods:  Of 288 patients managed with UFE with PVA particles for uterine myoma or adenomyosis between 1998 and 2001, 94 patients were enrolled in this study. The age range of participants was 20–40 years. The data were collected through review of medical records and telephone interviews. Mean duration of follow-up duration was 35 months (range 22–60 months). Patients using contraception and single women were excluded, and the chance of infertility caused by possible spousal infertility or other factors was disregarded. Contrast-enhanced magnetic resonance imaging was performed in all patients before and after UFE, and the size of PVA particles used was 255–700 μm.
Results:  Among 94 patients who underwent UFE with PVA, 74 were on contraceptives, 6 had been single until the point of interview, and 8 were lost to follow-up. Of the remaining 6 patients who desired future pregnancy, 5 (83%) succeeded in becoming pregnant (1 patient became pregnant twice). Of a total of 8 pregnancies, 6 were planned pregnancies and 2 occurred after contraception failed. Five deliveries were vaginal, and 2 were by elective cesarean. Artificial abortion was performed in 1 case of unplanned pregnancy. There was 1 case of premature rupture of membrane (PROM) followed by preterm labor and delivery of an infant who was small-for-gestational-age. After UFE, mean volume reduction rates of the uterus and fibroid were 36.6% (range 0 to 62.6%) and 69.3% (range 36.3% to 93.3%), respectively.

Conclusion:  Although the absolute number of cases was small, UFE with PVA particles ultimately did not affect fertility in the women who underwent the procedure.

 Article 3

Pregnancy Following Uterine Artery Embolization with Polyvinyl Alcohol Particles for Patients with
Uterine Fibroid or Adenomyosis

Man Deuk Kim,1 Nahk Keun Kim,2 Hee Jin Kim,1 Mee Hwa Lee
Departments of Diagnostic Radiology, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, 351 Yatap-dong, Bundang-gu, Sungnam-si, Kyonggi-do 463-712, Republic of Korea

Departments of Obstetric & Gynecology, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, 351 Yatap-dong, Bundang-gu, Sungnam-si, Kyonggi-do 463-712, Republic of Korea

Abstract

Purpose: To determine whether uterine fibroid embolization (UFE) with polyvinyl alcohol (PVA) particles affects fertility in women desiring future pregnancy.

Methods: Of 288 patients managed with UFE with PVA particles for uterine myoma or adenomyosis between 1998 and 2001, 94 patients were enrolled in this study. The age range of participants was 20–40 years. The data were collected through review of medical records and telephone interviews. Mean duration of follow-up duration was 35 months (range 22–60 months). Patients using contraception and single women were excluded, and the chance of infertility caused by possible spousal infertility or other factors was disregarded. Contrast-enhanced magnetic resonance imaging was performed in all patients before and after UFE, and the size of PVA particles used was 255–700 lm.

Results: Among 94 patients who underwent UFE with PVA, 74 were on contraceptives, 6 had been single until the point of interview, and 8 were lost to follow-up. Of the remaining 6 patients who desired future pregnancy, 5 (83%) succeeded in becoming pregnant (1 patient became pregnant twice). Of a total of 8 pregnancies, 6 were planned pregnancies and 2 occurred after contraception failed. Five deliveries were vaginal, and 2 were by elective cesarean. Artificial abortion was performed in 1 case of unplanned pregnancy. There was 1 case of premature rupture of membrane (PROM) followed by preterm labor and delivery of an infant who was small for-gestational-age. After UFE, mean volume reduction rates of the uterus and fibroid were 36.6% (range 0 to 62.6%) and 69.3% (range 36.3% to 93.3%), respectively.

Conclusions: Although the absolute number of cases was small, UFE with PVA particles ultimately did not affect fertility in the women who underwent the procedure.

Polyvinyl alcohol (PVA) particles are commonly used for UFE because of their high embolization effect. However, the effects of UFE with PVA particles on fertility and a woman's ability to maintain an intrauterine gestation are still uncertain. Only a few reports exist that concern pregnancy and UFE with PVA particles. Moreover, many gynecologists and interventionalists are reluctant to perform UFE in patients desiring future pregnancy. Some experts have tried gelatin sponge particles instead of PVA particles in women of childbearing age, but this technique has not yet been generally accepted. The aim of this study was to determine whether UFE with PVA particles affects fertility in patients desiring future pregnancy.

Materials and Methods
Of 288 patients at CHA General Hospital in Korea managed with UFE using PVA particles for uterine myoma or adenomyosis between 1998 and 2001, 94 were enrolled in this study. ranged in age from 20 to 40 years. We excluded women >40 years.

CardioVascular Published Online: 4 August 2005 and Interventional Radiology Cardiovasc Intervent Radiol (2005) 28:611–615

Article 4

Pregnancy after fibroid treatment

Women can conceive and carry a child after uterine artery embolisation (UAE), a treatment for uterine fibroids.

Uterine artery embolisation (UAE) that cuts off blood to the benign tumours, is usually considered suitable only for women who have finished having babies. But pregnancy may be possible after the treatment.

Nonetheless, women who become pregnant after UAE should be closely monitored for abnormal development of the placenta.

UAE is recognised as an alternative to hysterectomy for women with symptomatic fibroids, but little is known about the effect of UAE on fertility and pregnancy.

Researchers from the University of Toronto, USA reported pregnancies and deliveries among 555 women who underwent UAE as an alternative to hysterectomy as part of a clinical trial. The average age of the participants was 43 years, but 31 per cent were younger than 40.

The investigators report that 21 of the women conceived after the procedure, and three of the women became pregnant twice.

The findings suggest that women can definitely get pregnant after UAE. It would not be true if they were told that they couldn’t. It could cause a lot of problems if they are not using any contraception.

Twenty-three of the 24 pregnancies were conceived spontaneously. There were four spontaneous abortions, a rate of about 17 per cent, which is similar to that of the general population. There were a total of 18 live births. Fourteen of these were term births and four were pre-term births. There were nine vaginal births and nine caesarean deliveries. There were 3 cases of abnormal placental development.

Hence women who become pregnant after UAE should be followed closely.

Obstetrics and Gynecology, December 2004

Article 5

Pregnancy after uterine artery embolization for

leiomyomata: A series of 56 completed pregnancies

Woodruff J. Walker, FRCR, Simon J. McDowell, MBCHB
Departments of Radiology and Obstetrics and Gynaecology, The Royal Surrey County Hospital, Guildford, UK Received for publication November 4, 2005; revised April 5, 2006; accepted April 17, 2006

Objective: This study was undertaken to evaluate the incidence and outcome of pregnancies after uterine artery embolization (UAE) for symptomatic uterine fibroids.

Study design: A retrospective analysis of all pregnancies after UAE by a single interventional radiologist.

Results: Fifty-six completed pregnancies were identified in approximately 1200 women after UAE. One hundred eight patients were attempting to become pregnant and 33 of these became pregnant. Thirty - three (58.9%) of the 56 pregnancies had successful outcomes. Six (18.2%) of these were premature. Seventeen (30.4%) pregnancies miscarried. There were 3 terminations, 2 stillbirths, and 1 ectopic pregnancy. Of the 33 deliveries, 24 (72.7%) were delivered by cesarean section. There were 13 elective sections and the indication for 9 was fibroids. There were 6 cases of postpartum hemorrhage (18.2%). Conclusion: Compared with the general obstetric population, there is a significant increase in delivery by cesarean section and an increase in preterm delivery, postpartum hemorrhage, miscarriage, and lower pregnancy rates. When taking into account the demographics of the study population, these results can be partly explained. There were no other obstetric risk identified.

Uterine artery embolization (UAE) is a recognized treatment for symptomatic uterine fibroids, as described in numerous reports since 1995.Information on its effects on fertility and infertility, however, is limited. Advice often given to women with uterine fibroids who desire to retain fertility is to avoid UAE. Pregnancy after UAE has been described in the literature in the form of case reports, and a review article, some  retrospective series 7-9 and one retrospective cohort study comparing UAE with laparoscopic myomectomy. In December 1996, a prospective observational study was established to evaluate UAE in the management of symptomatic uterine fibroids. Most of the cases have been carried out at the Royal Surrey County Hospital with a minority performed privately at The London Clinic. All procedures were performed by a single interventional radiologist (W.W.). Pregnancy after UAE has been reported previously from this ongoing study, with a smaller population. To our knowledge, 60 women have conceived after UAE. This article describes the outcomes of those pregnancies.

Study was performed at The Royal Surrey County Hospital, Guildford, UK. * Reprint requests: Woodruff J. Walker, The Royal Surrey County Hospital, Egerton Road, Guildford, Surrey .UK.
American Journal of Obstetrics and Gynecology (2006) www.ajog.org
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Material and methods

During the period December 1996 to May 2005 approximately 1200 women underwent bilateral UAE as described in our previous publication. Ethical committee approval was obtained before December 1996. All
patients after embolization were sent a screening questionnaire. Information requested included: actively or previously attempted conception, not attempting conception, use of contraceptives, fertility problems before or after embolization, and other treatments offered by their primary gynecologist. If no reply was forthcoming, an additional questionnaire was sent out at 2 months, and if still no response, the patients were telephoned and the form filled out by a research assistant. All these initial forms were either returned or discussed over the telephone if incomplete or unreturned. An additional questionnaire was sent to these women seeking information on pregnancy outcome, age at delivery, complications of antenatal, intrapartum and postpartum periods, mode of delivery, reason for assisted delivery, other surgical procedures, birth weight, and length of lochia. Of these, 3 forms remained incomplete from the miscarriage group. Sixty pregnancies were identified in 48 women. Four of these pregnancies were ongoing, therefore excluded from further evaluation. Several women had been pregnant twice, one 3 times, and one 4 times. The women were from multiple locations throughout the United Kingdom. In complicated cases, reference was made to the patients’ medical records after their consent.

Results

From the approximately 1200 responses, 108 women had been seeking at some time to become pregnant, and 33 of these 108 women became pregnant at least once regardless of outcome. Eighteen women had unintentionally become pregnant; 30.5% of women wishing to become pregnant were successful regardless of outcome, and at least once after embolization. Of the 60 pregnancies, 19 had prior subfertility or infertility investigation, ranging from 18 months to 8 years. Twelve of these went on to have successful pregnancies. There was 1 successful in vitro fertilization (IVF) pregnancy. One other woman postembolization failed to become pregnant with IVF, but was successful later without IVF. Thirty-five pregnancies were first conceptions. There were 33 (58.9%) successful live births in 27 women. Twenty-seven (81.8%) of the 56 pregnancies delivered at term (R37 weeks’ gestation), and 6 (18.2%) premature (!37 weeks). There were 17 (30.4%) miscarriages, 3 (5.4%) terminations, 2 (3.6%) stillbirths, and 1 (1.8%) tubal ectopic.

Many of the patients had treatment for fibroids before and/or after embolization. Pre-embolization, 2 had previous open myomectomy, 2 had hysteroscopic resections, and 3 had laser ablation. Two had undergone ‘‘combined’’ procedures. This consisted of UAE before myomectomy in the same day and which aimed to virtually eliminate blood loss and kill any fibroids that would be difficult to remove surgically. Postembolization, 5 required hysteroscopic resection and 1 required a laparoscopic myomectomy. Of the 27 women with successful pregnancies, 14 had been previously offered hysterectomy as the only treatment option. The mean age at cessation of all pregnancies was 37.44 (SD 3.90). The mean for the miscarriage group was 38.75 (SD 4.43), and for the successful pregnancies 36.30 (SD 3.34). Of the miscarriages, 13 were early, or first trimester. One was second trimester (19 weeks), and for 3 cases the gestation at miscarriage was unavailable. In the first trimester miscarriages, 5 had a spontaneous miscarriage and 7 underwent evacuation for retained products of conception (ERPC). One required a second ERPC after developing infection for retained products of conception and a second required syntocinon for abnormal blood loss. The second trimester miscarriage was a 19-week missed miscarriage, which was revealed on ultrasound scan after a cessation in fetal movements. No cause was found for the miscarriage and post mortem examination was normal. This patient required a curettage for excessive vaginal bleeding after delivery. There were 3 terminations, 2 for social reasons, and 1 at 25 weeks’ gestation for trisomy 21. The 1 case of ectopic pregnancy was managed by salpingectomy at 6 weeks. There were 2 stillbirths. The first was at 33 weeks’ gestation, and was found to have a true knot in the cord. The second was at 37 weeks’ gestation in a woman who had had a previous successful pregnancy after embolization, delivered by a cesarean. During this subsequent pregnancy she had severe abdominal pain develop at 35

Twenty (60.6%) of the successful pregnancies had morning sickness. Eight (24.2%) of the 33 successful pregnancies had first-trimester bleeding, and 5 (15.2%) had second-trimester bleeding. There were 4 cases of third-trimester bleeding. Of these, 2 had major bleeds; one required admission from 29 weeks, and the other had an emergency cesarean for placental abruption. One woman was found to have a placenta previa. Another 5 had low-lying placentas. These migrated upward before 20 weeks’ gestation. There were 2 cases of proteinuric hypertension. The first was at 26 weeks’ gestation. Treatment was commenced for the HELLP syndrome and the patient had an emergency cesarean section at 27 weeks. The second was at 29 weeks’ gestation and required cesarean section at 33 weeks. There were 4 cases of pregnancy-induced hypertension, none of which required admission to hospital. There were 3 cases of premature rupture of membranes. The first was at 32 weeks’ gestation in a patient who had undergone 2 intrauterine fetal blood transfusions, and was subsequently found to have chorioamnioitis. The second was at 33 weeks’ gestation in a patient who had a septate uterus and activated protein C resistance caused by factor V leiden coagulopathy. She had been treated with low molecular weight heparin. The third occurred at 31 weeks’ gestation in a first conception. No cause was found and there were no associated factors identified. There was 1 case of intrauterine growth retardation (IUGR) requiring a cesarean section at 33 weeks’ gestation for impaired uterine artery blood flow.

Data for all pregnancy complications are shown in Table I. Six infants were born prematurely, 2 before 30 weeks’ gestation. The average premature gestation was 32.17 (SD 3.06) weeks. These cases are described in Table II. The mean birth weight for term infants was 3.53 kg (SD 0.63). The mean maternal age at delivery for premature deliveries was 36.83 (SD 4.07). Nine (27.3%) of women with successful outcomes delivered vaginally and 24 (72.7%) by cesarean section. Five of the 6 premature deliveries were by cesarean, therefore of those deliveries at term (R37 weeks), 19 (70.4%) of 27 were by cesarean section. Thirteen (54.2%)

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Comment
Pregnancy after UAE is well documented. There are valid concerns regarding the effect of embolization on those women wishing to retain fertility, and on the pregnant uterus. The numbers of patients who have become pregnant remains relatively small, meaning information for medical staff to convey to prospective UAE candidates is limited or incomplete.

A review in 2004 advised that until further data are available, laparoscopic myomectomy, open myomectomy, or hysteroscopic resection constitutes the standard of care in patients desiring future fertility. However, such cases may be difficult, particularly where there are numerous interstitial and/or submucous fibroids, and recurrence rates may be higher than 60%.

Fibroid embolization has the advantage over myomectomy in that it kills all the fibroids in 1 procedure, which then shrink or, in some cases, are passed vaginally. Our current series is the largest series to date of pregnancies after embolization for uterine fibroids. In this article we do not attempt to compare UAE with myomectomy, its object is to present the incidence of pregnancy, outcomes, and complication rates.

The population in this series is approximately double of that in the previous series. The demographics of the population have remained similar, but with higher numbers of normal, uncomplicated pregnancies. It is important to emphasise that the population involved is not a cohort typical of the general obstetric population. The mean age for all pregnancies at cessation was extremely high at 37.44 years. There are known associations between fibroids, subfertility, pregnancy loss, and pregnancy complications. Advanced maternal age adversely affects ovarian function, causing a decline in the number of good quality oocytes, resulting in chromosomally abnormal conceptions that rarely develop further. Of the women who became pregnant, 39.5% had some form of investigation for infertility before embolization.

Of 108 patients attempting to become pregnant, 33 were successful. Also, 58% of all pregnancies (including ongoing) were first conceptions, and these patients generally have higher rates of pregnancy- related complications. The information for this study was primarily obtained from patient questionnaire(s). Patients had pregnancy care from all over the United Kingdom, making it difficult to obtain medical records in all cases. Only in complicated cases were the medical records sought out. Optimally, all records should be perused. If there was confusion in the questionnaire, patients were telephoned by an obstetrically trained medical practitioner. Also, in the initial questionnaire, women were not asked if they had a history of subfertility, only if they had been attempting pregnancy or intending to attempt pregnancy. The reason for this was that most patients were advised other treatment regimens if desiring to keep their fertility. Only those who achieved pregnancy after embolization were sent a second questionnaire detailing any history of subfertility. From our study other comments relating to previous infertility, treatment and cause, cannot be made. Overall, most pregnancy complications were within normal ranges for the general obstetric population. The rate of miscarriage was high at 30.4%. The Royal College of Obstetrics and Gynaecology gives a 10% to 15% risk of spontaneous miscarriage. Rates of miscarriage increase 2- to 3-fold over the age of 40 years. The mean age in the miscarriage group was 38.75 years, and the ages ranged from 30 to 50 years. Of our patients who miscarried, 7 were older than 40 years, and all but 2 were older than 35 years. The rates of miscarriage in our study are higher; however, this may be explained, or partly explained, by the increased maternal age. The rates of first-trimester vaginal bleeding for successful pregnancies was also at the upper limit for the normal obstetric population; however, this has reduced since our previous series11 from 40% to 24.2%. The continued moderately higher rate may again be due to the older age group in our study population with corresponding higher risk factors. It could also be due to differences in embolization technique, as in the initial 400 patients who were embolized with polyvinyl alcohol particles to the branch vessels of the uterine arteries and coils blocking or restricting flow in the main uterine arteries. Subsequent patients were embolized with particles only and without occlusion of the main uterine arteries. Thus, there may have been a possibility of ischemia to the normal uterus and this may have contributed to the slightly increased complication rate in the earlier cases. Also, increasing technical experience led to progressive improvement in the reliability and efficiency. There were 6 (10.7%) cases of low-lying placenta; however, only 1 failed to migrate. Fibroids and abnormal uterine shape can be associated with placenta previa, therefore theoretically one might expect the rates of 4 Walker and McDowell
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The overall rate of cesarean sections for England and Wales was 21.9% in 2001 and 2002. This demonstrates that this conservatism is not without reason. The Goldberg study10 found rates of cesarean high in both the UAE group (63%) and the laparoscopic myomectomy group (59%). The Ontario multicenter trial9 found cesarean rates of 50%. The Goldberg study10 also found high rates of malpresentation in 4 of 35 cases (11%). Fibroids are linked with both malpresenation17 and preterm labor,18 probably by distorting the uterine cavity. Our study identified 2 of 33 (6.1%) malpresentations, and 1 face presentation, a rate that is not increased. Postpartum hemorrhage was increased at 18.2%. Current evidence linking fibroids with postpartum hemorrhage is inconsistent. One large multicenter study has concluded fibroids are an independent risk factor for increased postpartum blood loss. There was 1 case of abnormal placentation, a placenta previa. The Ontario trial identified 3 cases of abnormal placentation, all of which had postpartum hemorrhage and the Goldberg study found a low rate of postpartum hemorrhage at 6%. We have not been able to find evidence that adequately corrects for age and the presence of fibroids. Our study found an increased risk of postpartum hemorrhage that has not been replicated in other studies, but this may be explained by age and the presence of fibroids.

The overall pregnancy rate for women wishing to become pregnant is 30.5% (33/108). This is much lower than that reported for pregnancy rate after laparoscopic myomectomy. A review by Poncelet et al20 in 2002 of myoma and infertility showed that within 24 months of surgery almost 60% of patients spontaneously conceived. It should be noted, however, that many of our patients would have been unsuitable for laparoscopic myomectomy, (ie, with 1 or 2 suitably positioned fibroids !8 cm), and most of our patients were only offered UAE if they had fibroids that were considered not amenable to laparoscopic or hysteroscopic resection. Many of our patients had difficult multiple complex fibroids and had been rejected by referring gynecologists for other procedures. Fourteen, in fact, had been offered hysterectomy. The object of this study was not to compare myomectomy with the efficacy of myomectomy versus fibroid embolization. The latter would require a randomized controlled trial, in which patients were very accurately matched particularly with regard to the magnetic resonance imaging evaluation of the number and types and size of fibroids involved. The main purpose of this article is to present the outcome of pregnancies after embolization and their complication rates. The cases in which other fibroid treatment procedures were performed are therefore included, as these patients were still exposed to the ‘‘risk’’ of embolization of the uterine arteries.

From our results, it is evident women can conceive after UAE, and a successful pregnancy outcome is possible. Successful pregnancy outcome was finally achieved in some patients having previous failed myomectomies and in 14 patients only offered hysterectomy. Two patients with virtually untreatable fibroid disease achieved pregnancy after combined procedure. Rates of miscarriage, preterm delivery, and postpartum hemorrhage were higher than the general obstetric population; however, this population of patients is not typical and has additional risk factors. From our data, it appears that there is an increase in miscarriage, preterm deliveries, and postpartum hemorrhage, which may be explained by the increased age of the study population and the history of a fibroid uterus. There is a significantly increased rate of cesarean section compared with the national average.
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We believe that our results have influenced the way in which patients with fibroids wanting to become pregnant should be counseled. For those patients with large and/or multiple submucous or interstitial fibroids where resection would be difficult and likely to recur and in those with failed previous fibroid surgery, UAE should be considered as an option for treatment with advice that a successful pregnancy outcome is possible after UAE. A randomized controlled trial of myomectomy versus UAE is required to optimally evaluate pregnancy rates but such a trial would be an enormously complex undertaking to accurately match patients in the 2 groups.