Objective
We sought to examine the reproductive outcomes of 52 women with classical bladder exstrophy.
Study Design
This was an observational study with cross-sectional and retrospective arms.
Results
The average age of the sample was 33 years (range, 17–63). Of those who had tried, 19/38 (66%) had conceived. A total of 57 pregnancies (3 sets of twins) were reported for the 19 patients and resulted in 34/57 live births (56%), 21/57 miscarriages (35%), 1/57 (2%) termination, and 4/57 (7%) stillbirths or neonatal deaths. Four deliveries resulted in major complications including 1 transection of the ureter (4%), 1 fistula formation (4%), and 2 postpartum hemorrhages (8%). There were 2 admissions to intensive care, one for urinary sepsis and another for massive obstetric hemorrhage.
Conclusion
Fertility is impaired in women with bladder exstrophy. Pregnancy is high risk both for the mother and baby. Delivery should be at a tertiary referral obstetric unit with urology cover. In the majority of cases planned cesarean section is the most appropriate mode of delivery.
Classical bladder exstrophy (BE) is a rare and complex malformation of the genitourinary tract affecting females and males. Prevalence is estimated to be in the region of 1 in 50,000 live births. Advances in reconstructive surgery have led to higher survival rates. Furthermore, with the advent of the Mitrofanoff procedure, which is a conduit between the urinary bladder and skin that allows clean self-catheterization, patients are increasingly able to remain continent. Thus far clinical care has focused upon urinary function and preservation of the renal tract.
There is very little information on the social and psychological developmental trajectories of young adults diagnosed with BE. It can be surmised that they have aspirations to relationships, sexual intimacy, parenthood, and quality of life that are similar to those of their peers. For women with BE, pregnancy and childbirth is potentially realistic. However, little is known about fertility, pregnancy, and delivery outcomes associated with BE.
The most extensive review on the topic was published by Clemetson more than half a century ago. The paper was a literature review of obstetric outcomes in 64 pregnancies in 45 women. The maternal mortality rate was found to be 4%, stillbirth rate 14%, and infant survival rate 77%. Data of Clemetson spanned some 200 years (1724 through 1958) and so the adverse maternal and neonatal outcomes were thought to be historic and not applicable to modern clinical management. Subsequent to Clemetson, approximately 100 further pregnancies can be identified in the literature in 74 women. According to these reports, fertility rates were encouraging. Cesarean delivery was performed in two thirds of the cases. Pelvic organ prolapse was found to be a common complication. Difficult surgical delivery was reported in only 1 case. Severe preeclampsia and placental abruption was also reported for 1 case. The majority of these papers were case reports and small series with short-term follow-up and have been uniformly positive and reassuring about fertility and obstetric outcomes in women with BE. A recent larger series of 22 pregnancies in 14 women found good outcomes although reported high rates of genital prolapse after delivery.
But does the literature justify the embedded optimism? The aim of the current study is to evaluate the fertility and obstetric outcomes in the so far largest cohort of female patients with classical BE.
Materials and Methods
This was an observational study in 2 parts: (1) participants completed a postal questionnaire on urinary continence, sexual function, and fertility and pregnancy outcomes; and (2) a retrospective review of the medical notes was carried out to collect information on demographics, medical and surgical history, and fertility and pregnancy outcomes.
The study was undertaken at a specialist center for congenital anomalies of the urogenital tract in the United Kingdom. Ethics approval was obtained (Joint Royal National Orthopoedic Hospital/The Institute of Orthopaedics & Musculoskeletal Science Research Ethics Committee no. 08/H0724/39). Patients were identified from the hospital urology and gynecology database. Permission was sought from the patients to obtain hospital records from both the specialist center and other treating hospitals.
Participants
A total of 52 female patients aged >16 years with BE were identified from departmental databases over a 35-year period. The average age of the 52 women was 33 years (range, 17–63). Women with epispadias and cloacal exstrophy were excluded from the study. Of the 52 women identified, 8 could not be contacted due to death (1), moving abroad (2), and lost to follow-up (5). Therefore 44 women were eligible for the questionnaire part of the study.
Results
Medical notes were available for review in all 52 patients. In addition, 28/44 returned completed questionnaires (64%). Data are taken from a combination of medical records and questionnaires. Where possible, information from questionnaires was confirmed by reviewing the hospital notes.
Surgical history
The 52 women had an average of 8 major surgical reconstructive episodes (range, 3–15 operations). All of them had undergone a primary surgical repair in childhood. In addition, 42/52 (81%) also required bladder augmentation, and 11/52 (21%) required concurrent pelvic osteotomies. A Mitrofanoff procedure was used in 27/52 (54%) either primarily or subsequently.
Of the 19 women who became pregnant, 13 had a Mitrofanoff and 3 had an ileal conduit. The remaining 3 women passed urine urethrally either spontaneously or by self-catheterization.
Six of the 52 patients (12%) had a müllerian duplication of whom 2 had partial hysterectomies in childhood, ie, removal of 1 uterus of a double müllerian system. Four other patients out of the sample of 52 had also undergone hysterectomy at the average age of 34 years; 3 of them had never been pregnant and 2 had hysterectomy for chronic pelvic pain and endometriosis refractory to medical management. Of the total sample of 52, 34 patients (65%) had undergone a vaginoplasty. In all cases this was a typical midline posterior introitoplasty to widen the posterior fourchette as previously described.
General health
In all, 17/52 (33%) had impaired renal function on creatinine and glomerular filtration rate screening. Of the 52 women, 39 (75%) were identified as continent of urine, 10 (19%) were not, and in 3 (6%) it was unknown. Recurrent urinary tract infections (UTI) requiring prophylactic antibiotics were reported by 34 (65%) patients. Eight (15%) patients were noted to have hypertension requiring treatment.
Fertility and conception
A total of 42/52 (81%) patients had been sexually active, 2/52 (4%) had not, and in 8/52 (15%) this information could not be ascertained. A total of 28/52 patients reported attempting conception and 19/28 (68%) were successful, although only 4/19 conceived naturally within 1 year and the remainder were delayed or required fertility treatment ( Table 1 ). In 4 patients assisted conception was offered and declined and 1 patient elected to adopt a child. Of the 2 patients with duplication of the uterus who had undergone partial hysterectomy in childhood, 1 of these had 4 pregnancies in the remaining horn. The other also had 1 uterine horn removed in childhood but was subsequently infertile due to adhesions to the contralateral tube and never achieved pregnancy despite fertility treatment. In the 19 patients who conceived, 57 pregnancies were reported and 3/57 were twin pregnancies. The miscarriage rate (35%) may be an overestimate as the standard “blue-line” pregnancy test gives about a 50% false-positive rate when used on urine stored in any form of intestinal reservoir. Some women may, therefore, have believed they were pregnant and interpreted a subsequent late period as a miscarriage.
| Outcome | Within 1 y | Delayed | Fertility treatment |
|---|---|---|---|
| Conception | 4 (21%) | 15 (79%) | 5 (26%) |
| Investigated for infertility | Endometriosis – 4 | IVF – 4 (successful in only 1 case) | |
| Tubal obstruction – 3 | Ovulation induction – 1 | ||
| Unilateral oophorectomy – 3 | |||
| PCOS – 2 | |||
| Unknown – 3 |
Obstetric outcomes
There were 57 pregnancies (3 sets of twins) in 19 patients, resulting in 34 live births (56%), 21 miscarriages (35%), 1 termination (2%), and 4 stillbirths or neonatal deaths (7%).
Antenatal complications
In the antenatal period pregnancies were complicated by pelvic floor prolapse in 8/19 women (42%); this was managed by bed rest and ring pessary. Uterine prolapse occurs in up to 50% of women with exstrophy and, as this may occur even without a pregnancy, the pregnancy may have unmasked a problem that would have occurred anyway. Six women (32%) had hypertension or preeclampsia during pregnancy and 1 postpartum eclamptic fit was reported. Of the 6 women who developed hypertension or preeclampsia, all but 1 woman had impaired renal function prior to pregnancy.
Two pregnancies were complicated with placental previa or accreta. The placenta previa was in a first pregnancy and resulted in an uncomplicated cesarean delivery. The placenta accreta was in a third pregnancy following 2 cesarean sections, with delivery resulting in massive postpartum hemorrhage requiring admission to the intensive care unit postdelivery.
Urological antenatal complications
Of the 19 women, 12 (63%) had significant urological complications in pregnancy 9 with singleton pregnancies and all 3 with twin pregnancies. All of these 12 presented with intractable urinary infection due to obstruction either of the ureter or bladder outflow.
Seven women (37%) had urinary retention requiring catheterization during their pregnancy. Four of the 7 (24%) were singleton pregnancies and had upper tract obstruction requiring nephrostomy tubes or stenting of the ureters. All 3 twin pregnancies required ureteric stenting or a nephrostomy tube due to urinary tract obstruction secondary to pressure effects. All twin gestations suffered from recurrent UTI and in 1 patient this led to admission to the intensive care unit for urinary sepsis.
Obstetric outcomes
All but one of the singleton pregnancies had a good outcome ( Table 2 ). The exception was with a baby born at 30 weeks by an emergency cesarean section. There was difficulty in delivering the fetus because of the adhesions from the bladder reconstruction. Despite the procedure being performed by a consultant obstetrician with urology support available, the baby died. This illustrates the danger of emergency cesareans in patients who have undergone complex urinary tract reconstructions.
| Outcome | Singleton pregnancies n = 54 | Twin pregnancies n = 3 | Total, n (%) |
|---|---|---|---|
| Live birth | 31 | 3 a | 34 (56) |
| Miscarriage | 21 | 21 (35) | |
| Termination | 1 | 1 (2) | |
| Stillbirth | 1 | 3 b | 4 (7) |
| Total | 54 | 6 | 60 (100) |
a Three live babies from 2 pregnancies;
The twin pregnancies were delivered at 26, 33, and 37 weeks and accounted for 3 of the neonatal deaths. Both twins born at 26 weeks died of complications resulting from extreme prematurity. The twins born at 33 weeks were the product of intracytoplasmic sperm injection and both babies were well at delivery and needed no neonatal support. Of the twins born at 37 weeks, 1 died shortly after birth due to a congenital anomaly (gastroschisis), which was not associated with the mother having BE. The other twin of this pregnancy was normal and survived without any long-term sequelae.
The median gestational age of all the live births was 37 weeks (mean 36 weeks, range, 29–39 +4 weeks). Nine (26%) were delivered premature (<37 weeks), and 4 of these at ≤30 weeks. All patients delivered by cesarean section of which 3 were emergencies, and all but 2 were planned. Two of the emergency cesarean deliveries resulted in 2 neonatal deaths due to delivery delay where labor preceded the date of elective delivery.
Three classical cesarean sections were performed due to adhesions in the lower segment; one of these was an emergency cesarean. A general surgeon or urologist was present in all but 4 planned cesarean deliveries, and surgical backup was present for 2 of the 3 emergencies despite them being performed overnight. Four elective cesareans resulted in major complications including 1 transection of the ureter, 2 postpartum hemorrhages (8%), and 1 uterocutaneous fistula formation, which was only recognized later.
Results
Medical notes were available for review in all 52 patients. In addition, 28/44 returned completed questionnaires (64%). Data are taken from a combination of medical records and questionnaires. Where possible, information from questionnaires was confirmed by reviewing the hospital notes.
Surgical history
The 52 women had an average of 8 major surgical reconstructive episodes (range, 3–15 operations). All of them had undergone a primary surgical repair in childhood. In addition, 42/52 (81%) also required bladder augmentation, and 11/52 (21%) required concurrent pelvic osteotomies. A Mitrofanoff procedure was used in 27/52 (54%) either primarily or subsequently.
Of the 19 women who became pregnant, 13 had a Mitrofanoff and 3 had an ileal conduit. The remaining 3 women passed urine urethrally either spontaneously or by self-catheterization.
Six of the 52 patients (12%) had a müllerian duplication of whom 2 had partial hysterectomies in childhood, ie, removal of 1 uterus of a double müllerian system. Four other patients out of the sample of 52 had also undergone hysterectomy at the average age of 34 years; 3 of them had never been pregnant and 2 had hysterectomy for chronic pelvic pain and endometriosis refractory to medical management. Of the total sample of 52, 34 patients (65%) had undergone a vaginoplasty. In all cases this was a typical midline posterior introitoplasty to widen the posterior fourchette as previously described.
General health
In all, 17/52 (33%) had impaired renal function on creatinine and glomerular filtration rate screening. Of the 52 women, 39 (75%) were identified as continent of urine, 10 (19%) were not, and in 3 (6%) it was unknown. Recurrent urinary tract infections (UTI) requiring prophylactic antibiotics were reported by 34 (65%) patients. Eight (15%) patients were noted to have hypertension requiring treatment.
Fertility and conception
A total of 42/52 (81%) patients had been sexually active, 2/52 (4%) had not, and in 8/52 (15%) this information could not be ascertained. A total of 28/52 patients reported attempting conception and 19/28 (68%) were successful, although only 4/19 conceived naturally within 1 year and the remainder were delayed or required fertility treatment ( Table 1 ). In 4 patients assisted conception was offered and declined and 1 patient elected to adopt a child. Of the 2 patients with duplication of the uterus who had undergone partial hysterectomy in childhood, 1 of these had 4 pregnancies in the remaining horn. The other also had 1 uterine horn removed in childhood but was subsequently infertile due to adhesions to the contralateral tube and never achieved pregnancy despite fertility treatment. In the 19 patients who conceived, 57 pregnancies were reported and 3/57 were twin pregnancies. The miscarriage rate (35%) may be an overestimate as the standard “blue-line” pregnancy test gives about a 50% false-positive rate when used on urine stored in any form of intestinal reservoir. Some women may, therefore, have believed they were pregnant and interpreted a subsequent late period as a miscarriage.
