Pregnancy After Fibroids

Fibroids and Pregnancy


The trial at the Royal Surrey County Hospital and London Clinic represents the largest world series of pregnancies following Uterine Artery Embolization (UAE) (1,3,7). It is important to remember the population group in our trial is atypical i.e. older and with other additional risk factors compared with the general obstetric population. Most of our patients had been rejected for surgery, many had very large fibroid masses and they were an older age group, 37.2 years average (Walker Bratby 2007(1)). 14 patients with successful pregnancies had only been offered hysterectomy. In the series of 2,000 patients we have had 105 pregnancies and the results of these pregnancies are summarised in Table 1. As of February 2010

Table 1

Pregnancies post fibroid embolization 105
Successful deliveries 65
Ongoing pregnancies 2
Miscarriages 27 - Rate 25%
Ectopic pregnancy 1
Abortion (unwanted pregnancy) 8
Baby died through knot in cord 1
Still birth 37 weeks 1

However, further to the above the total is now 76 successful completed pregnancies after UAE. Data under current analysis. Miscarriage and complication rates: The spontaneous miscarriage rate and other complications outlined in Table 1 are no higher than would be expected allowing for age and fibroid status. Subsequently we updated our results(1) analysing 67 pregnancies (our miscarriage rate was 22%).

Debate over UAE vs myomectomy in patients desiring pregnancy

Some concerns have been expressed with regard to pregnancy and miscarriage rates following fibroid embolization. The problem is that early reviews of pregnancy outcomes were based on old data when the technique was evolving. There has only been one randomised control trial with myomectomy versus embolization (Mara et al) from the Czech Republic but the numbers were very small and in addition it is obvious from the results that radiologists inexperienced in the technique of embolization were performing the embolizations. This is evidenced by the fact that there is an unacceptably high rate of failure to infarct the dominant fibroid at 30% i.e. nearly one third of patients. You would expect this percentage to be ½-1% at most.

In addition there were a very high number of unilateral embolizations which usually do not work. They changed the particle size during the series (obviously believing that they were using the wrong sized particles and, in addition, they used a type of particle which we would not recommend). The FEMME Study which looked at this trial reported 'borderline significant and the study was not powered for any outcomes' but even that study did not take into account the obvious lack of experience of the radiologists performing the procedure and the poor technical embolization results.

There has been one other article by Homer and Saridogan which also suggested higher rates. However the article is again flawed; for example they quote our miscarriage rate as as being 34% whereas in reality if they had read the article from 2007 they would see that we were reporting a miscarriage rate of 22%. In other words the results are misquoted. In addition, our early series were performing embolizations on patients with very difficult fibroids referred when gynaecologists did not wish to perform myomectomy because the cases were too difficult; for example 14 of our patients who has successful pregnancies had only been offered hysterectomy. We had an average age which was high i.e. 37.5(1) years and we know that miscarriage rates and obstetric problems increase with age.

We were treating often very large fibroids. Despite this our results were acceptable and not above matched groups. We have now had 76 successful completed pregnancies and we are currently analysing our pregnancy data and, in particular, our more recent results when our patients have been less extreme in terms of their fibroid disease and in a situation where there has been an increase in experience, expertise and an improvement in technique. If we look at recent publications on pregnancy rates (McLucas; Firovznia at al; Pisco et al) the results have been good (see as an example table below). Pisco et al: Fertility and Sterility 2010.

Results for 74 women:

  • 44 pregnancies (59.5%) - 5 ongoing (11.3%), 39 finished pregnancies (88.7%)
  • 33 live births (84.6%)
  • Miscarriage rate 10.3%
  • Caesarian section rate 66%
  • Average age 36
  • All types of fibroid treated

Pregnancy rates and miscarriage rates are hugely influenced by age and severity of fibroid disease. There is no doubt that patients with more difficult disease tend to get referred for fibroid embolization. Thus our research shows that it is scientifically invalid as is often stated by various bodies and in areas of the literature to claim that no patient wishing to become pregnant should have fibroid embolization. It should be noted that a number of our patients who had had failed myomectomies had successful pregnancies following UFE and some patients who had UFE required myomectomy.

References

  • 1. Walker WJ, Bratby . Magnetic Resonance Imaging (MRI) Analysis of Fibroid Location in Women Achieving Pregnancy After Uterine Artery embolization. Cardiovascular interventional Radiology - August 2007
  • 3. Walker WJ, McDowell SJ. Pregnancy after uterine artery embolization for leiomyomata: at series of 56 completed pregnancies. American Journal of Gynecology & Obstetrics November 2006 195(5) 1266-71
  • 7. TT Carpenter, WJ Walker. Pregnancy following uterine artery embolization for symptomatic fibroids: a series of 26 completed pregnancies. British Journal of Obstetrics and Gynaecology, 112, pp321-325 March 2005.

Our results in 56 pregnancies published July 2006 in the American Journal of Obstetrics and Gynecology can be downloaded here: 'Pregnancy-Paper' Our subsequently updated series Walker & Bratby(1) can be accessed on the internet.

Pregnancy after uterine artery embolization for leiomyomata: a series of 56 completed pregnancies

American Journal of Obstetrics and Gynaecology (2006) Pregnancy after uterine artery embolization for leiomyomata: A series of 56 completed pregnancies Woodruff 3. Walker, FRCR,a,* Simon 3. McDowell, MBCHBb 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 Uterine artery embolization. Uterine fibroid embolization.

Leiomyomata Pregnancy 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: 56 completed pregnancies were identified in approximately 1200 women after UAE. 108 patients were attempting to become pregnant and 33 of these became pregnant. 33 (58.9%) of the 56 pregnancies had successful outcomes. 6 (18.2%) of these were premature. 17 (30.4%) pregnancies miscarried.

There were 3 terminations, 2 stillbirths, and 1 ectopic pregnancy. Of the 33 deliveries, 24 (72.7%) were delivered by caesarean section. There were 13 elective sections and the indication for nine was fibroids. There were 6 cases of postpartum haemorrhage (18.2%).

Conclusion: Compared with the general obstetric population, there is a significant increase in delivery by caesarean section and an increase in pre-term delivery, postpartum haemorrhage, 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. © 2006 Mosby, Inc. All rights reserved.

Uterine artery embolization (UAE) is a recognized treatment for symptomatic uterine fibroids, as described in numerous reports since 1995.1-5 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 fibroids embolization has been described in the literature in the form of case reports, and a review article.6 Some retrospective series7-9, and one retrospective cohort study comparing UAE with laparoscopic myomectomy.10 In December 1996, a prospective observational study was established to evaluate UAE in the management of symptomatic uterine fibroids.4 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 (Woodruff J. Walker).

Pregnancy after embolization has been reported previously from this ongoing study, with a smaller population.11 To our knowledge 60 women have successfully achieved pregnancy after UAE. This article describes the outcomes of those pregnancies.

Material and methods

During the period December 1996 to May 2005 approximately 1200 women underwent bilateral UAE as described in our previous publication.4 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 wasmade to the patients' medical records after their consent.

Table I Pregnancy complications

Complication No. (% Rate) Rate from literature
(General obstetric population)
Miscarriage 17 (30.4%) 10% - 15% 21
Morning Sickness 20 (60.6%) 50% - 70% 22
First-trimester bleeding 8 (24.2%) 25% 23
Second-trimester bleeding 5 (15.2%) NA
Third-trimester bleeding 4 (12.1%) 17.6% 24
Placenta previa 1 (3.0%) 0.4% 25
Proteinuric hypertension 2 (6.1%) 8% - 18% 26
Premature rupture of
membranes
3 (9.1%) 2% - 3.5%
IUGR 1 (3.0%) 5%
Preterm delivery 6 (18.2%) 5% - 10% 28
Postpartum haemorrhage 6 (18.2%) 5.4% - 13% 19,29

Results

From the approximately 1,200 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. 35 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 ( greater than or equal to R37 weeks’ gestation), and 6 18.2%) premature (less than 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. Preembolization, 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 diffcult to remove surgically. Post embolization, 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 weeks but was not seen by an obsterician until 37 weeks. At emergency cesarean she was found to have a ruptured uterus through her previous cesarian scar. 20 (60.6%) of the successful pregnancies had morning sickness. 8 (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.

Table II Preterm deliveries

Gestation
(weeks)
Wtkg) Indication
for delivery
Complications/
treatment
Mode of Delivery
34 1.86 SROM, activated protein
C resistance
Jaundice, antibodies Cesarian
27 0.99 HELLP Ventilation, PDA, No
ongoing problems
Cesarian
32 2.18 Parvovirus/SROM/
Chorioamnioitis
Hepatosplenomegaly,
infection, antibiotics
Cesarian
31 1.51 SROM Oxygen, no ongoing
problems
Vaginal
33 1.65 PET Oxygen, feeding tubes Cesarian
36 1.96 Abruption Reuscitation, oxygen Cesarian

SROM, Spontaneous rupture of membrane; PET, pre-eclamptic toxaemia. 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).

Table III Caesarean sections

Em, Emergency; LSCS, Lower segment caesarean section; El, elective; CTG, cardiotocography; 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 caesarean, therefore of those deliveries at term (~37 weeks), 19 (70.4%) of 27 were by cesarean section. Thirteen (54.2%) of the caesarean sections were elective, and 11(45.8%) were as an emergency. Fibroids were the indication for 9 of the 13 elective caesareans. The emergency caesareans had a variety of indications. Of the emergency caesarean sections, 5 attempted vaginal deliveries. One of the vaginal deliveries required ventouse for poor maternal effort. Indications for all caesarean sections are shown in Table III. There were 5 cases of postpartum haemorrhage, 2 requiring blood transfusion. There were no cases of abnormal placentation other than the previa described previously. The mean length of lochia was 4.63 weeks. Two women did not provide details and for 5 women lochia was not yet completed. There were 2 cases of presumed endometritis and 1 of postnatal depression.

Comment

Pregnancy after uterine artery embolization is well documented. There are valid concerns regarding the effect of fibroids embolization on those women wishing to retain fertility, and on the pregnant uterus. The numbers of patients who have become pregnant after uterine embolization remains relatively small, meaning information for medical staff to convey to prospective uterine artery embolization 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.6 However, such cases may be difficult, particularly where there are numerous interstitial and/or sub mucous fibroids, and recurrence rates may be higher than 60%.12 Fibroid embolization has the advantage over myomectomy pre pregancy after embolization in that it kills all the fibroids in one procedure, which then shrink or, in some cases, are passed vaginally. Our current series is the largest series to date of pregnancies after fibroid embolization for uterine fibroids. In this article we do not attempt to compare uterine artery embolization with myomectomy, its object is to present the incidence of pregnancy after embolization, outcomes, and complication rates. The population in this series is approximately double of that in the previous series. 11 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, sub fertility, pregnancy loss, and pregnancy complications. The information for this study was primarily obtained from patient questionnaires. 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 sub fertility, 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 fibroids embolization were sent a second questionnaire detailing any history of sub fertility. 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.14 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 series 11 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 placenta previa to be higher than the general obstetric population. The Ontario multicenter trial 9 had 3 cases of placenta previa (14.3%), 2 of which had antepartum haemorrhage that required delivery. The relevance or our increased rate of placenta previa is debatable with only a single case identified. Abnormal placentation can be a contributory factor to proteinuric hypertension and IUGR. The rate of proteinuric hypertension and IUGR in our series are below the general obstetric population. Of the 3 cases of premature rupture of membranes, 2 are likely to be associated with other factors (an intrauterine septum and intrauterine blood transfusions). Therefore, the adjusted rate is 3.0%. This is within the normal range. The rate of premature delivery (18.2%) is higher than the rates for the general obstetric population (5%- 10%). 15,16 It has been documented that women older than 35 years have approximately double the risk of premature delivery.16 The mean maternal age for the pre-term group was 36.8 years. The pre-term delivery rate is similar to the Ontario trial 9 4 of 18 (22.2%) and the Goldberg study 10 5 of 32 (16%). The laparoscopic myomectomy group in the Goldberg study had a much lower rate of pre-term delivery at 3%. Although the numbers are still small, it appears that rates of pre-term delivery are higher than the general obstetric population. This may well be explained by increased maternal age. The rate of caesarean section was extremely high at 72.7%. The rate of elective caesarean is also high at 39.4%. The indication in 9 of the elective sections was either partly or solely caused by fibroids, whereas in the emergency group, only 1 had fibroids as the indication. This may demonstrate that of those who elect to attempt a normal vaginal delivery following pregnancy after embolization will not necessarily then need an emergency section with fibroids as the indication. Understandably, obstetricians take a conservative approach to managing labour in these patients because of limited information on pregnancy after uterine fibroids embolization. However, the rate of caesarean sections in those going to term and planning a normal vaginal delivery remains well above normal rates at 42.9% (6/14). The overall rate of caesarean 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 caesarean high in both the UAE group (63%) and the laparoscopic myomectomy group (59%). The Ontario multicenter trial9 found cesarean rates of 50%. The Goldberg study 10 also found high rates of mal-presentation 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%) mal presentations, and 1 face presentation, a rate that is not increased. Postpartum haemorrhage was increased at 18.2%. Current evidence linking fibroids with postpartum haemorrhage is inconsistent.17 One large multicenter study has concluded fibroids are an independent risk factor for increased postpartum blood loss.19 There was 1 case of abnormal placentation, a placenta previa. The Ontario trial9 identified 3 cases of abnormal placentation, all of which had postpartum haemorrhage and the Goldberg study found a low rate of postpartum haemorrhage 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 haemorrhage 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 less than 8 cm), and most of our patients were only offered embolization 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 gynaecologists 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 randomised 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 pregnancy after embolization and the 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 become pregnant after fibroid embolization, 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 fibroids achieved pregnancy after combined procedure(s). Rates of miscarriage, preterm delivery, and postpartum haemorrhage 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 haemorrhage, 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 caesarean section compared with the national average. Taking the demographics of the study population into account, we did not identify any other major obstetric risks. We believe that our results have influenced the way in which patients with fibroids wanting to become pregnant should be counselled. For those patients with large and/or multiple sub mucous or interstitial fibroids where resection would be difficult and likely to recur and in those with failed previous fibroid surgery, embolization 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 after fibroid embolization but such a trial would be an enormously complex undertaking to accurately match patients in the two groups.

Acknowledgments and References

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Condensation:
Pregnancy after uterine artery embolization for symptomatic fibroids has higher rates of caesarean section, miscarriage, preterm delivery, and postpartum haemorrhage but without other major obstetric risks.