Fertility and pregnancy outcome following pelvic arterial embolization for severe post-partum haemorrhage. A cohort study

L.J. Salomon1, R. de Tayrac1, V. Castaigne-Meary1, F. Audibert1, D. Musset2, R. Ciorascu2, R. Frydman1 and H. Fernandez1,3

Service de 1 Gynécologie-Obstétrique and 2 Radiologie, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, 157 rue de la Porte-de-Trivaux, 92141 Clamart cedex, France

3 To whom correspondence should be addressed. e-mail: herve.fernandez{at}abc.ap-hop-paris.fr


    Abstract
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
BACKGROUND: Pelvic arterial embolization is a safe, effective life-saving procedure in post-partum haemorrhage, but little information is yet available about its impact on menstruation and fertility. METHODS: A cohort of 28 women who underwent pelvic embolization for post-partum haemorrhage in our tertiary centre was studied. Patients were contacted by telephone to obtain long-term outcome for menstruation, clinical signs of estrogen insufficiency, desire for fertility and subsequent pregnancies. RESULTS: We found no menstrual abnormalities or signs of early menopause among the 17 patients we were able to reach. Six women expressed a clear desire for subsequent pregnancies. Five patients reported a total of six pregnancies (one biochemical pregnancy, one early miscarriage and four deliveries). The four patients with complete gestations gave birth to healthy babies, but post-partum haemorrhage recurred for all and led to two hysterectomies. No undesired pregnancies occurred. CONCLUSIONS: Embolization in post-partum haemorrhage appears to be a safe procedure that does not impair subsequent menstruation and fertility. Recurrence of severe post-partum haemorrhage may occur at subsequent deliveries.

Key words: embolization/fertility/menstruation/post-partum haemorrhage/pregnancy


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Post partum obstetrical haemorrhage is a major cause of maternal morbidity and mortality (Gilbert et al., 1987Go). Many disorders can cause it, including uterine atony or rupture, retained products of conception, placental abnormalities or lower genital tract lacerations. In all cases, primary management involves manual exploration of the uterus, suturing lacerations and the use of uterotonic agents such as oxytocin and/or prostaglandin analogues. In a few cases, these local measures do not control bleeding and other treatment is needed to stop the haemorrhage. Conservative surgical treatment such as selective ligation of uterine or internal iliac arteries (Evans and McShane, 1985Go; O’Leary 1995Go; Ledée et al., 2001Go) can be attempted but the results are controversial (Chattopadhyay et al., 1990Go). Patients for whom conservative treatment is ineffective may end up requiring a lifesaving hysterectomy, with its accompanying loss of fertility and its psychological effects.

Recent developments in percutaneous angiographic embolization techniques offer a safe and effective means of controlling pregnancy-related haemorrhages (Pelage et al., 1998Go; Hansch et al., 1999Go). This method appears to avoid the risks inherent in emergency anaesthesia and surgical exploration, although Pirard et al. (2002Go) have recently published a report of uterine necrosis and sepsis after vascular embolization for post-partum haemorrhage due to placenta accreta. This procedure may also preserve reproductive ability (Stancato-Pasik et al., 1997Go). Adequate documentation of the reappearance of normal menstruation and fertility is not yet available, however, and comprehensive reports are needed before we can conclude that fertility after angiographic embolization for post-partum haemorrhage is not a problem. The recent report for fibroid embolization by Chrisman et al. (2000Go) is cause for concern, even though it discusses a somewhat different technique. They found an incidence of post procedure ovarian failure considerably higher than that previously reported and observed clinical or laboratory signs of menopause in almost 15% of patients who underwent this procedure.

This cohort study was therefore undertaken to evaluate the effect on menstruation and fertility of angiographic embolization performed in severe post-partum haemorrhage.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
From July, 1995 to December, 2000, the staff at our tertiary centre performed angiographic embolization of the pelvic arteries for severe post-partum haemorrhage in 28 patients. During the same period, we performed 48 surgical ligations of pelvic arteries and eight hysterectomies for this indication. Seven of these 28 patients were referred for management of the post-partum haemorrhage, and 21 were delivered in our department.

In all cases, primary management included manual exploration of the uterus, suturing lacerations and use of oxytocin and prostaglandin analogues, or both. Blood transfusions were performed when there was clinical evidence of inadequate oxygen-carrying capacity or of an haemoglobin concentration <70 g/l, and fresh frozen plasma was transfused in the presence of consumption coagulopathy and persistent bleeding.

Once the treating obstetrician decided that local measures were unlikely to control the haemorrhage and that embolization was the best choice, a qualified well-trained radiologist performed the angiographic embolizations with the patient sedated but conscious. Our general rule was that embolization was considered the first-line treatment for uterine atony occurring after vaginal delivery or after those Caesarean sections in which local conditions were unfavourable for artery ligation or occurring >24 h after the first episode of haemorrhage.

Embolization involved selective catheterization, preferably of the uterine or internal iliac arteries (depending on the pelvic angiogram). Absorbable gelatine sponges and 5 French visceral selective catheters were used. Angiography confirmed the complete embolization of the bleeding vessel. Subsequently, uterotonic agents were administered; further treatments were performed when necessary. Details on the procedures and measures performed to stop post-partum haemorrhage were collected from the medical records.

During February, 2002, one of the authors attempted to contact all the patients from this cohort to determine the long-term outcome of this procedure. Patients were asked about resumption of menses, menstrual histories, pelvic pain and dyspareunia, modification of sexual function and clinical symptoms of estrogen insufficiency such as hot flushes and/or vaginal dryness. Finally, patients were also asked about their desire for subsequent pregnancies, attempts to conceive and results. Data about the progress and outcome of these subsequent pregnancies were obtained from the medical records.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
During the study period, 28 patients underwent pelvic artery embolization for severe post-partum haemorrhage. In one case, post-partum haemorrhage followed early second trimester termination of pregnancy after in-utero death at 13 weeks. For all other cases, the mothers’ median age was 32 years (range 18–43) and the baby’s median gestational age 38 weeks (range 27–42). Median birth weight was 3400 g (range 770–4000). Five of these patients had twin pregnancies (all dichorionic). Altogether, 24 pregnancies were spontaneous, while four involved assisted reproductive technologies (three ICSI, one intrauterine insemination). All but seven gave birth in our centre. Delivery was performed by Caesarean section in 10 cases. The mean time between delivery and effective pelvic embolization was 7.3 h (range 1–26). The cause of the haemorrhage was uterine atony in 20, placenta accreta in five and genital lacerations in three cases. The embolization involved uterine arteries in 18 and internal iliac arteries in seven cases. In three cases the internal iliac artery was embolized on one side and the uterine artery on the other. Absorbable gelatine sponges were used in all cases.

One patient, referred to us after delivery, died in our centre soon after her arrival and embolization. A computer tomodensitometric scan showed evidence of ischaemic cerebral injuries due to heart failure before her arrival. Blood units were needed in 20 cases, with a mean of 6 blood units transfused. Fresh frozen plasma was needed in 11 cases. No patients required additional surgical treatment to stop the haemorrhage (no artery ligation, no hysterectomy).

We were able to contact 17 of the 27 remaining patients at follow-up periods ranging from 12 to 80 months (Table I). In these 17 cases, all resumed menstruation after 4–16 weeks (mean time 9 weeks) and considered these menses comparable, in duration and quantity, to those before pregnancy (in the absence of oral contraception). None reported pelvic pain or dyspareunia, change in sexual function, nor did any describe clinical symptoms of menopause, such as hot flushes or vaginal dryness.


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Table I. Patients follow-up.
 
One patient (number 15) required femoral artery dilatation and stent placement one year after internal iliac artery embolization because of clinical symptoms of femoral artery subtotal occlusion. One patient (number 8) still suffers from buttock pain and paresthaesia after uterine artery embolization.

Six of these patients wanted another child. In this group, five patients have had six pregnancies (Table I): one early miscarriage (number 14), four deliveries (numbers 1, 10, 14 and 15) and one biochemical pregnancy in a patient (number 12) needing assisted reproductive technology, as she had done for the pregnancy that occasioned the embolization; the post-embolization reproductive assessment did not indicate ovarian failure. The mean period until pregnancy (measured from decision to attempted conception) ranged from 3–15 months (Table I).

In the four complete gestations, pregnancy was uneventful until delivery. In all cases, fetal growth and well-being were assessed by routine ultrasonography and were normal. The uteroplacental Doppler ultrasound examinations routinely performed at the second trimester sonographic examination were normal in all cases. These four patients gave birth to healthy babies of normal weight for gestational age. In two cases (numbers 10 and 15), adherent placenta caused a recurrence of post-partum haemorrhage and required local measures (manual removal of placenta, exploration of genital tract, uterine massage) and prostaglandins to stop the haemorrhage. No blood transfusions were needed. The initial cause of haemorrhage for these two cases which indicated index embolization were uterine atony. In the other two cases (numbers 1 and 14), however, placenta accreta caused the recurrence of post-partum haemorrhaging and neither local measures nor medical treatment, including blood transfusions (6 and 9 blood units respectively), could stop the haemorrhaging: hysterectomies were performed in both cases. The initial cause of haemorrhage for these two cases which indicated index embolization were uterine atony and placenta accreta.


    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Transcatheter arterial embolization has emerged as a highly effective percutaneous technique for controlling acute obstetric haemorrhage (Mitty et al., 1993Go; Pelage et al., 1999Go; Ledée et al., 2001Go). It avoids surgical exploration and the consequent prolonged hospitalizations and complications. Moreover, it can preserve fertility. Stancato-Pasik et al. (1997Go) followed up 12 patients after embolization therapy for post-partum haemorrhage and reported three pregnancies. More recently, McLucas et al. (2001Go) reported 17 pregnancies in 14 women among the 139 patients who underwent fibroid embolization and stated that they wanted to conceive. Embolization for fibroids and post-partum haemorrhage cannot be directly compared, but both techniques aimed to preserve fertility for young women. Furthermore, the particles used for fibroid embolization are not absorbable, are smaller and are preferentially injected in the vessel that feeds the fibroid, in many centres.

We were able to follow up, over a relatively long term, 17 women who underwent post-partum embolization. In all cases, menses resumed soon after procedure. No women reported any differences in menses or pain compared with before the pregnancy, or any clinical symptoms of early menopause. These results are consistent with the absence of effects of post-partum embolotherapy on ovarian function and activity. Six of the 17 patients we followed up wanted another child. Up to now, five have become pregnant. One patient who wants more children has not yet conceived, but she has currently been trying for only 4 months. Four pregnancies have gone to term; all were strictly uneventful until delivery. In particular, uteroplacental and umbilical Doppler examinations as well as fetal growth were normal. These findings suggest that the embolization did not harm either uterine or ovarian function.

Strikingly, post-partum haemorrhage recurred in all four deliveries. We are aware that the risk of recurrence of post-partum haemorrhage is high but it is worthwhile to look at the cause of these recurrences. The placenta was involved in all cases: in two cases it adhered to the uterus, thus causing haemorrhaging, despite active management of the third stage of labour. Manual removal was necessary to separate the placenta from the uterus. In the two other cases, placenta accreta prevented any possibility of manual removal and thus required a life-saving hysterectomy.

To our knowledge, this is the largest cohort study assessing long-term outcome and ability to conceive after embolotherapy in post-partum haemorrhage. The newness of the procedure and its possible effect on menstruation and ovarian function make it particularly important to examine its long-term outcome. Indeed, accidental embolization of ovarian vessels via uterine–ovarian anastomoses can result in the loss of ovarian function, as Chrisman et al. (2000Go) have reported in connection with fibroid embolizations, but, in the case of post-partum haemorrhage, no similar accident has been described. Such accidental embolization may also be more frequent with unusual ovarian vasculature, as when ovarian arteries branch off from the internal iliac arteries (Kozik, 2000Go). No such abnormalities were found in our cohort. Moreover, the patients after post-partum embolization are always much younger that the patients treated for fibroids, and this may be one reason for the difference in ovarian failure rates.

The radiation exposure involved in the procedure can also be deleterious for ovarian function. The gonads are among the organs most sensitive to radiation and are in the direct path of the beam during embolization. Nonetheless, several studies suggest that the radiation exposure is comparable with that in routine diagnostic imaging procedures (Andrews et al., 2000Go; Nikolic et al., 2000Go).

While subsequent pregnancies clearly appear to be possible, they also appear to carry a high risk of recurrence for post-partum haemorrhage. The mechanism by which haemorrhage recurs has not yet been elucidated. We hypothesize however that the previous embolization might in some way modify implantation and the trophoblast invasion in subsequent pregnancies, therefore explaining the involvement of the placenta in all the recurrences. Although the uterus can be damaged by either radiation or persistent vascular occlusion, this is a less likely cause, since it is not as radio-sensitive as the ovaries, and embolization is performed with absorbable particles. We might speculate, however, that a uterus damaged by an unknown mechanism might allow excessive cytotrophoblast invasion, leading in turn to defective decidual development and abnormally strong placental attachment. Histological examination of the uterus in the two cases with hysterectomies confirmed the placenta accreta diagnosis but could not help in understanding its possible link with the previous embolization. Obviously, the small number of patients in our studies renders the determination of causality still speculative, all the more, as the incidence of recurrent post-partum bleeding is high. However, in our experience of 21 pregnancies after hypogastric artery ligation (Nizard et al., 2003Go), we did not observe severe recurrence of post-partum haemorrhage.

We also note that many patients did not want more children. This might be related to one weakness of our study—the high rate of patients lost to follow-up (10 of 27), due to the length of the study period. While we may have missed some subsequent pregnancies, we do not think that the patients who moved should have induced bias in our results. Of the 10 patients with only one child, nine did not desire another pregnancy. The patients who had successful deliveries before this serious complication seemed more likely to want another child.

In conclusion, our study confirms previous reports (Vedantham et al., 1997Go; Pelage et al., 1999Go; Hansch et al., 1999Go) that embolization is a safe, effective life-saving procedure in post-partum haemorrhages. Moreover it does not appear to affect menstruation or fertility. Pregnancies occur spontaneously in patients who so desire but recurrence of severe post-partum haemorrhage may occur. Further studies are needed to assess the risk of recurrent post-partum haemorrhage. A larger cohort study to compare outcome for subsequent pregnancy after artery ligation and angiographic embolization might help in improving conservative management of post-partum haemorrhage.


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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
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Submitted on October 8, 2002; accepted on January 3, 2003.