Pediatr Surg Int (2014) 30:773–781 DOI 10.1007/s00383-014-3535-5
ORIGINAL ARTICLE
The influence of anorectal malformations on fertility: a systematic review E. C. P. Huibregtse • J. M. Th. Draaisma • M. J. Hofmeester • K. Kluivers • I. A. L. M. van Rooij I. de Blaauw
•
Accepted: 18 June 2014 / Published online: 27 June 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose This systematic review aims to give an overview of available evidence concerning the influence of anorectal malformations (ARM) on fertility. Methods We conducted a search in PubMed, EMBASE and Cochrane Library conformed to the PRISMA standards. All studies reporting on fertility and ARM were included. Results 2,905 studies were identified. Based on title, abstract and full text, nine articles on 429 patients remained to answer the research question. Childbirth rate was the only reported outcome parameter to describe fertility. An overall childbirth rate of 27 % (range 0–57 %) was found. Mean age at time of study ranged from 23 to 35 years. There was no statistical significant difference in childbirth rate between female and male patients, based on seven
E. C. P. Huibregtse M. J. Hofmeester I. de Blaauw (&) Department of Pediatric Surgery, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands e-mail: [email protected] J. M. Th. Draaisma Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands K. Kluivers Department of Gynecology and Obstetrics, Radboud University Medical Center, Nijmegen, The Netherlands I. A. L. M. van Rooij Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands I. de Blaauw Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
studies (p = 0.45). Patients with a more complex type of ARM (imperforated anus without fistula, rectourethral bulbar and prostatic fistulas, rectobladderneck fistulas and cloacal malformations) had a lower childbirth rate compared to healthy controls, whereas in patients with a less complex ARM (rectoperineal or rectovestibular fistula) the childbirth rate was similar to healthy controls. Patients with a more complex type of ARM had a significant lower childbirth rate than patients with a less complex type of ARM (18 vs 47 %, respectively) (p = 0.0001). When further dividing these patients by gender, this difference was only seen in female patients (p = 0.04). Conclusion In patients with a more complex type of ARM a lower childbirth rate was found compared to healthy controls and patients with a less complex type of ARM. The latter was only seen in female patients. However, conclusions concerning fertility in ARM patients have to be taken with caution due to limited quality of the studies. Further investigation is recommended. Keywords Childbirth
Anorectal malformations Fertility
Introduction Anorectal malformations (ARM) comprise a wide spectrum of congenital conditions, characterized by an atresia or narrowing of the anorectal canal, with or without a fistula to neighboring organs. The malformations vary between minor defects with an excellent functional prognosis and complex defects with poor functional prognosis. ARM are associated in 40–70 % with other congenital malformations [1–4], such as those present in the VACTERL association (vertebral, anal, cardiac, trachea-
123
774
esophageal, renal, limb anomalies) or other genital and sacral malformations, but may also occur isolated [1–3]. The incidence of ARM is approximately 2–6 births per 10,000 births worldwide [5]. The initial therapy to obtain the function of the rectum is by surgery, which most often takes place in the first 2 years of life. Improvement in medical care has led to decreased morbidity and mortality, but complete functionality may still not be obtained, often leading to some degree of physical and social morbidity. The vast majority of patients with an ARM reaches adulthood nowadays. In this phase of life the influence of ARM on fertility plays a role. It is known that persons with all kinds of congenital malformations have lower childbirth rates than those without [6, 7]. The term fertility is defined as the capacity to conceive or to induce conception and to produce offspring. Fertility is influenced by many factors, including different topics ranging from the quality of the sperm cells and oocyts to the maintenance of a pregnancy. Fecundability or time-topregnancy is the best term to describe fertility. The reasons for impaired fertility are complex and multifactorial in ARM patients. These reasons may be related to the associated congenital malformations of the genital organ, spine and spinal cord, the surgery performed in the small pelvis, as well as the psychosocial problems caused by fecal incontinence, constipation, urinary incontinence and impaired sexual function. Although fertility is a very important issue in life, as has been indicated by parents’ societies [8], literature on this topic is not abundant. Therefore, it is relevant to juxtapose evidence and draw (preliminary) conclusions, which can be used to inform patients, parents and health care workers. The aim of our study was therefore to conduct a systematic review on the influence of ARM on fertility.
Methods Search strategy A literature search was performed in September 2013 in PubMed, the Cochrane Library and EMBASE to obtain all publications on studies that reported on ARM and fertility. The PubMed search used the Medical Subject Headings (MeSH) terms ‘‘Congenital abnormalities’’, ‘‘Anal Canal’’, ‘‘Anal’’, ‘‘Rectum’’, ‘‘Fistula’’, ‘‘Perineum’’, ‘‘Cloaca’’ and the text words ‘‘Anorectal malformation*’’, ‘‘Abnormalities’’, ‘‘Malformations’’, ‘‘Anus’’, ‘‘Anal’’, ‘‘Rectum’’, ‘‘Rectal’’, ‘‘Anorectal’’, ‘‘Fistula’’, ‘‘Perine*’’, ‘‘Vestibu*’’, ‘‘Rectoperineal’’, ‘‘Rectovestibular’’, ‘‘Rectourethral’’, ‘‘Rectovesical’’, ‘‘Rectobladderneck’’ and ‘‘Cloaca’’ combined with the MeSH terms ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Pregnancy rate’’, ‘‘Pregnancy’’, ‘‘Reproductive
123
Pediatr Surg Int (2014) 30:773–781
techniques’’, ‘‘Quality of life’’ and the text words ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Subfertility’’, ‘‘Time-to-pregnancy’’, ‘‘Pregnancy rate’’, ‘‘Pregnancy’’, ‘‘Fecundity’’, ‘‘Fecundability’’, ‘‘Reproductive techniques’’, ‘‘Quality of life’’ and ‘‘QoL’’. The Cochrane search used the same MeSH terms and text words. The EMBASE search used the EMTREE terms ‘‘Anorectal malformation’’, ‘‘Anus’’, ‘‘Rectum’’, ‘‘Anal canal’’, ‘‘Anus fistula’’, ‘‘Rectum fistula’’, ‘‘Rectovaginal fistula’’, ‘‘Perineum’’, ‘‘Fistula’’, ‘‘Cloaca’’ and the text words ‘‘Anorectal malformation*’’, ‘‘Abnormalities’’, ‘‘Malformation*’’, ‘‘Rectum’’, ‘‘Rectal’’, ‘‘Anus’’, ‘‘Anal’’, ‘‘Anal canal’’, ‘‘Fistula’’, ‘‘Perine*’’, ‘‘Vestibu*’’, ‘‘Rectoperineal’’, ‘‘Rectovestibular’’, ‘‘Rectourethral’’, ‘‘Rectovesical’’, ‘‘Rectobladderneck’’ and ‘‘Cloaca’’, combined with the EMTREE terms ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Reproduction’’, ‘‘Childbirth’’, ‘‘Conception’’ ‘‘Fertilization’’, ‘‘Parity’’, ‘‘Pregnancy’’, ‘‘Pregnancy outcome’’, ‘‘Pregnancy rate’’, ‘‘Infertility therapy’’, ‘‘Quality of life’’, ‘‘Birth rate’’ and the text words ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Subfertility’’, ‘‘Pregnancy outcome’’, ‘‘Pregnancy rate’’, ‘‘Birth rate’’, ‘‘Pregnancy’’, ‘‘Fecundity’’, ‘‘Fecundability’’, ‘‘Childbirth’’, ‘‘Infertility therapy’’, ‘‘Quality of life’’ and ‘‘Timeto-pregnancy’’. Limits were set to articles on humans. We conformed to the PRISMA statement to achieve the highest standard in reporting items for a systematic review [9, 10]. Eligibility criteria All studies that reported on any outcome measure regarding fertility in patients with an ARM were included. Studies on cloacal exstrophy were excluded, because of the complexity of the malformation with involvement of the bladder. Furthermore, case reports, studies without access to the full text and studies not written in English were excluded. The references of included studies were reviewed to include useful studies that might have been missed with the initial search (cross check). Study selection The study selection was dependent on four different steps; search strategy, study screening, study eligibility and study inclusion. They were all performed by one researcher (EH), under supervision of two medical experts (IdB, JD). Data extraction A predefined checklist was used. Data on study design, number and type of population, definition used to describe
Pediatr Surg Int (2014) 30:773–781
fertility, percentage of childbirth and described subtypes of ARM were collected. The Krickenbeck classification was used to define the subgroups of ARM patients, based on fistula type and the clinical use [11]. It was designed to make comparison of follow-up studies possible. However, the Wingspread classification was the most frequently used classification of ARM in literature. It classified different types of ARM in high, low and intermediate and contained a separate group for cloacal and rare malformations [12]. We therefore reclassified patients from the Wingspread classification, into the Krickenbeck classification as described in Table 1. ‘The more complex ARM group’ consisted of imperforated anus without fistula, rectourethral bulbar and prostatic fistulas, rectobladderneck fistulas and cloacal malformations, whereas ‘the less complex ARM group’ consisted of rectoperineal and rectovestibular fistulas.
Statistical analysis Descriptive analyses were performed. Childbirth rate was calculated by cumulating the number of patients with children of their own divided by the total patients included in the studies, when possible. 95 % confidence intervals were calculated around the mean. Using the Fisher’s exact test, we statistically tested differences in childbirth rate between males and females and between the less complex ARM group and the more complex ARM group.
775
Results The search resulted in 1,213 abstracts in PubMed, 23 abstracts in the Cochrane library and 1,669 abstracts in EMBASE. After exclusion of duplicates, 2,291 abstracts remained. Based on title, 2,145 abstracts were excluded. Based on abstract, another 111 abstracts were excluded. Reasons for exclusion were that articles were not reporting on ARM (n = 27), not reporting on fertility (n = 71), reporting on cloacal exstrophy (n = 5), concerning case reports (n = 18) or not written in English or no full text was available (n = 17). One study was included by cross checking references. Eventually, nine articles were left to answer our research question (Fig. 1). These nine studies were published between 1992 and 2013 in developed countries. Two out of the nine studies made a comparison with healthy controls [13, 14], the others studies were case series from a certain hospital or country. The total number of patients included ranged from 21 to 83 per study, in total 163 females and 120 males with ARM. The mean age at time of the study ranged from 23 to 35 years. All studies presented a differentiation in subtypes of ARM, but there was variation in reported classifications. Only one study used the Krickenbeck classification [8]. Childbirth rate was used to describe fertility in all studies and was defined as the percentage of persons who have children of their own. One study also mentioned the fertility rate (number of children per woman) [15]. Information on the number of patients who intended to conceive was available in two studies [16, 17]. Table 2 shows the
Table 1 Translation of the Wingspread classification to the Krickenbeck classification Type of classification
Krickenbeck classification
Wingspread classification High
Males
Intermediate
Rectoperineal fistula
Low
Cloaca
X
Rectourethral bulbar fistula
X
Rectourethral prostatic fistula
X
Rectobladderneck fistula
X
Imperforated anus without fistula
X
Complex and unusual defects Female
Rectoperineal fistula Rectovestibular fistula
X X
Cloaca with short common channel (\3 cm)
X (intermediate)
Cloaca with long common channel ([3 cm)
X (high)
Imperforated anus without fistula Complex and unusual defects
X
Cloacal exstrophy, covered cloacal exstrophy
X
Posterior cloaca
X
Associated to presacral mass Rectal atresia
X
123
776
Pediatr Surg Int (2014) 30:773–781
Fig. 1 Flow chart of study selection
study characteristics and Table 3 provides an overview of the results. Hundred and fifteen of the 429 patients with ARM had children of their own. This makes the overall childbirth rate 27 % [8, 13–20]. The two studies comparing patients with healthy controls showed that in patients with a less complex ARM, childbirth rate was similar, whereas in patients with a more complex ARM, childbirth rate was lower compared to controls [13, 14]. No differentiation was made between female and male patients. In seven out of nine studies, childbirth rate could be distracted by gender. There was no statistical significant difference in childbirth rate between female (19 %) and male patients (15 %) (p = 0.45). Childbirth in the more complex ARM group could be separated from the less complex ARM group, also in seven out of nine studies. This resulted in more childbirth in patients with a less complex ARM [57 of the 122 patients had children (47 %)] [13, 15, 19] than in patients with a more complex ARM [31 of the 176 patients had children (18 %)] (p = 0.0001) [14, 15, 17–20]. When dividing these patients by gender, a difference in childbirth rate in male patients with a less (10 %) and more (11 %) complex ARM was not found
123
(p = 1.00). However, female patients with a more complex ARM did have a lower childbirth rate than female patients with a less complex ARM (14 vs 39 %, respectively). This difference was statistical significant (p = 0.04). Cloacal malformation was the only subtypes of ARM that could be studied as a separate group [8, 15, 17–20]. Of the 79 included patients with a cloaca, 12 had offspring of their own (15 %). Mean age of the patients studied ranged from 23 to 26 years.
Discussion There is a lower childbirth rate in female patients with more complex ARM, compared to female patients with less complex ARM. This result may be explained by the fact that the incidence of genital malformations is significantly increasing with an increased complexity of the ARM [21– 23]. In patients with a rectoperineal fistula, genital malformations are rare (0–3 %) [21, 23], whereas genital malformations are by definition associated with patients with cloacal malformations, the most complex malformations in females. In these patients, 30 % present with a
Definition used for fertility
Childbirth rate
Childbirth rate
Childbirth rate
Childbirth rate
Childbirth rate
References, country
Rintala [13], Finland
Rintala [14], Finland
Schmidt [8], Germany
Hassink [18], The Netherlands
Davies [16], United Kingdom
Table 2 Study characteristics
Case series using questionnaires
Case series using questionnaires
Case series using personal interviews
Case-control study using questionnaires
Case-control study using questionnaires
Study design and method of data collection
7 (16 %)
11 (37 %)
30 M
5 (13 %) 44 F
3 (16 %)
19 F
3 (9 %)
32 M
39 M
5 (22 %)
Cases: 13 (39 %) Controls: 21 (60 %)
Controls: 45 (57 %)
Cases: 48 (57 %)
Patients with children of their own, no. (%)
23 F
25 M
8F
30 M
53 F
Number of patients
25.6 (SD 0.6)
26.0 (range 18.1–56.9)
23 (range 18-56)
35.3 (SD 4.8)
35.2 (SD 4.1)
Mean age at time of study (years)
8 Unknow
16 Low
6 High
3 Unknown
17 Low
15 Cloaca
9 High
High
4 Others 2 Unknown
0 Anal stenosis
3 Imperforated anus
6 Cloaca (1/6 got children)
10 Vestibular
5 Rectovesical
19 Rectouretral
6 Perineal
1 Rectobulbar fistula
1 Atresia Recti
2 Anal agenesis
2 Rectovesical fistula
19 Rectourethral fistula
1 Cloacal extrophy
4 Rectovaginal fisula 3 Cloaca
14 Anocutaneous fistula
16 Anal stenosis
4 N-type rectovestibular fistula
38 Anovestibular/vulvar fistula
3 Anocutaneous fistula
8 Anal stenosis
Type of ARM included
Pediatr Surg Int (2014) 30:773–781 777
123
123
Fertility rate (children/ woman). Childbirth rate
Childbirth rate
Childbirth rate
Childbirth rate (pregnancies)
Mantoo [15], France
Iwai [19], Japan
Hendren [20], Massachusetts, US
Warne [17], United Kingdom
Case series using hospital charts
Case series using hospital charts
Case series using questionnaires or personal interviews
Case series using questionnaires
Study design and method of data collection
F female, M male, X not reported, SD standard deviation
Definition used for fertility
References, country
Table 2 continued
21 F
0 (0 %)
6 (25 %)
0 (0 %)
18 M
24 F
4 (36 %)
4 (13 %)
31 M
11 F
6 (29 %)
Patients with children of their own, no. (%)
21 F
Number of patients
24
X
25.8
29.3
28 (SD 9)
Mean age at time of study (years)
Cloaca
Cloaca
3 Low (0/3 got children)
5 Intermediate (0/5 got children)
10 High (0/10 got children)
4 Low (2/4 got children)
4 Intermediate (0/4 got children)
3 High (2/3 got children)
1 Unknown (0/1 got children)
18 Low (2/18 got children)
12 High (2/12 got children)
1 Unknown (1/1 got children)
14 Low (5/14 got children)
6 High (0/6 got children)
Type of ARM included
778 Pediatr Surg Int (2014) 30:773–781
Pediatr Surg Int (2014) 30:773–781
779
Table 3 Childbirth rate in female and male patients with an ARM, divided by type of ARM % of childbirth
Type of ARM
Female patients
39 % (95 % CI: 16–61 %) [15, 19]
Male patients
10 % (95 % CI: 0–22 %) [15, 19]
Female and male patients
47 % (95 % CI: 38–56 %) [13, 15, 19]
Rectoperineal fistula
Rectovestibular fistula
Rectourethral bulbar fistula
Imperforated anus without fistula
Rectourethral prostatic fistula
Rectobladderneck fistula
11 % (95 % CI: 3–19 %) [15, 18, 19] 18 % (95 % CI: 12–23 %) [14, 15, 17–20]
hydrocolpos in the newborn period, which can lead to infection and vaginal scarring and reduce fertility [24]. Furthermore, 40 % of the cloaca patients will have a double Mu¨llerian system [24]. In another study, Warne et al. found a normal uterine anatomy in only 12 of the 41 patients with a cloaca (29 %), the other patients had a unicornuate, bicornuate, double or absent uterus. All Mu¨llerian abnormalities are associated with increased rates of pregnancy loss and preterm delivery [25]. 29 % of patients with a cloaca presented themselves for gynecological examination with an obstructed uterus due to stenosis of persistent urogenital sinus or cervical stenosis [26]. The inadequate outflow of menstrual blood can result in secondary damage, e.g., endometriosis, leading to further infertility [25, 26]. In male ARM patients, cryptorchidism and hypospadias are the most common genital malformations. In patients with hypospadia, no convincing evidence has been described for impaired fertility [27]. Cryptorchidism is described in 19 % of the boys with an ARM [28]. The higher the level of ARM, the higher the incidence [28]. Paternity rates have been found reduced in one-third of the patients with bilateral cryptorchidism [29]. If the incidence of bilateral cryptorchidism increases with an increased complexity of ARM, a decreased childbirth rate is expected in patients with more complex ARM. Apparently, genital malformations in male patients have less influence on childbirth rate than in female patients, because difference in childbirth rate between less and more complex ARM in male patients was not seen in our study. In spite of the evolution in surgical management of ARM [30], a second possible reason for a decreased childbirth rate is the possibility of iatrogenic damage. Since the mid-1980s, most patients are operated by the posterior
Cloaca
Overall
15 % (95 % CI: 7–23 %) [15, 17–20]
19 % (95 % CI: 13–25 %) [8, 15–20] 15 % (95 % CI: 9–21 %) [8, 15, 16, 18, 19] 28 % (95 % CI: 24–33 %) [8, 13–20]
sagittal anorectoplasty (PSARP). This technique allows a direct visualization of the anatomy of the muscle complex and nerves of the pelvic floor are spared as much as possible [31]. In female patients with less complex ARM, complications such as scarring of the perineum or vagina may occur, but are seldom described. Further damage to the reproductive tract is even less likely. Female patients with more complex ARM, such as cloacas, require a more challenging operation, with the risk of complications such as ischemic vaginal atresia, stenosis, recurrent fistulas or injury to the Mu¨llerian structures. In 30 % an additional abdominal approach will be necessary [32]. Long-term outcome data on the effect of these complications are, however, limited. In male patients, surgery of the most frequent rectoperineal fistula, does normally not involve the exposure of the reproductive tract and will therefore not affect fertility rates. Surgical exposure during PSARP performed in the other types of ARM is closer to the ejaculatory ducts, seminal vesicals, prostate, vas deference and nerves, responsible for sexual function. Iatrogenic complication rate of the reproductive tract was however only 1.7 % (10 out of 572 patients) in a study by Hong et al. [33]. Longterm outcomes regarding fertility in these patients are not available. Another reason for a decreased childbirth rate in more complex ARM may be related to psychosocial aspects of functional disorders such as fecal incontinence, constipation, urinary incontinence and impaired sexual function. These disorders are more often present in patients with more complex ARM. Psychosocial consequences may influence sexual activity and therefore indirectly have an impact on childbirth, but high quality studies are lacking on this subject.
123
780
Comparing results of fertility in patients with ARM remains difficult, because of the several limitations of the studies included. Fertility in ARM patients should be properly assessed and compared with a sex-, age- and social-matched control group. This adequate comparison was performed in only two studies. Small patient groups were used that could have caused the wide variation in childbirth rate. The mean age of patients in the cohorts of our review was relatively young, whereas the mean age to become a parent is usually higher. This obviously leads to a lower childbirth rate, independent from ARM. Another limitation of most studies is the use of childbirth rate as measurements for fertility. Questionnaires, personal interviews and hospital charts were used to count childbirth in patients with ARM, but only two studies reported the number of patients who had actively been trying to conceive [16, 17]. In a study by Davies et al. [16], 7 out of 44 women had children; the other women had not yet tried to conceive. In a study by Warne et al. [17], no children were born, but only four patients had tried to conceive. When childbirth was measured only in patients who tried to have children, the childbirth rate would probably have been much higher. At last, the type of ARM and additional anomalies should be well documented in all patients to relate this with the outcome of fertility. We recommend further research and studies with a preferable prospective design, with larger (multicenter) patient groups, higher mean age, well documented type of ARM and additional anomalies, time-to-pregnancy or fecundability as outcome measurement and healthy controls, matched for age, gender, and social status as comparison group.
Conclusion The aim of our study was to investigate the influence of ARM on fertility. The more complex ARM types seem to have a lower childbirth rate than healthy controls and patients with less complex ARM. The latter was only seen in female patients. Possible explanations for these findings could be found in the additional genital malformations often seen in female patients, iatrogenic damage of surgery and psychosocial consequences of ARM related to sexual activity. Overall, caution should be taken with interpreting these results. Due to limited quality of the studies, it remains difficult to make an unequivocal statement on fertility in patients with ARM and the underlying causes. Further investigation is recommended.
123
Pediatr Surg Int (2014) 30:773–781
References 1. Wijers CH et al (2013) Anorectal malformations and pregnancyrelated disorders: a registry-based case-control study in 17 European regions. BJOG 120(9):1066–1074 2. Stoll C et al (2007) Associated malformations in patients with anorectal anomalies. Eur J Med Genet 50(4):281–290 3. Cuschieri A, E.W. Group (2002) Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 110(2): 122–130 4. Hassink EA et al (1996) Additional congenital defects in anorectal malformations. Eur J Pediatr 155(6):477–482 5. International clearing house for birth defects surveillance and research (2011). In: Annual report: with data for 2009. http://www. icbdsr.org/filebank/documents/ar2005/Report2011.pdf. Accessed 24 August 2012 6. Skjaerven R, Wilcox AJ, Lie RT (1999) A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children. N Engl J Med 340(14):1057–1062 7. Lie RT, Wilcox AJ, Skjaerven R (2001) Survival and reproduction among males with birth defects and risk of recurrence in their children. JAMA 285(6):755–760 8. Schmidt D et al (2012) Sexual function in adults with anorectal malformation: psychosocial adaptation. German Network for Congenital Uro-REctal Malformations (CURE-Net). Pediatr Surg Int 28(8):789–792 9. Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–e34 10. Moher D et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341 11. Holschneider A et al (2005) Preliminary report on the International Conference for the Development of Standards for the treatment of anorectal malformations. J Pediatr Surg 40(10): 1521–1526 12. Anorectal malformations in children: update 1988 (1988) Birth Defects Orig Artic Ser 24(4):1–604 13. Rintala R, Mildh L, Lindahl H (1992) Fecal continence and quality of life in adult patients with an operated low anorectal malformation. J Pediatr Surg 27(7):902–905 14. Rintala R, Mildh L, Lindahl H (1994) Fecal continence and quality of life for adult patients with an operated high or intermediate anorectal malformation. J Pediatr Surg 29(6):777–780 15. Mantoo S et al (2013) The impact of anorectal malformations on anorectal function and social integration in adulthood: report from a national database. Colorectal Dis 15(6):e330–e335 16. Davies MC et al (2010) Anorectal malformations: what happens in adulthood? BJU Int 106(3):398–404 17. Warne SA et al (2003) Long-term gynecological outcome of patients with persistent cloaca. J Urol 170(4 Pt 2):1493–1496 18. Hassink EA et al (1994) Quality of life after operatively corrected high anorectal malformation: a long-term follow-up study of patients aged 18 years and older. J Pediatr Surg 29(6):773–776 19. Iwai N et al (2007) Social quality of life for adult patients with anorectal malformations. J Pediatr Surg 42(2):313–317 20. Hendren WH (1998) Cloaca, the most severe degree of imperforate anus: experience with 195 cases. Ann Surg 228(3):331–346 21. Metts JC 3rd et al (1997) Genital malformations and coexistent urinary tract or spinal anomalies in patients with imperforate anus. J Urol 158(3 Pt 2):1298–1300
Pediatr Surg Int (2014) 30:773–781 22. Nah SA et al (2012) Anomalies associated with anorectal malformations according to the Krickenbeck anatomic classification. J Pediatr Surg 47(12):2273–2278 23. Rich MA, Brock WA, Pena A (1988) Spectrum of genitourinary malformations in patients with imperforate anus. Pediatr Surg Int 3:110–113 24. Levitt MA, Pena A (2010) Cloacal malformations: lessons learned from 490 cases. Semin Pediatr Surg 19(2):128–138 25. Rackow BW, Arici A (2007) Reproductive performance of women with mullerian anomalies. Curr Opin Obstet Gynecol 19(3):229–237 26. Levitt MA, Stein DM, Pena A (1998) Gynecologic concerns in the treatment of teenagers with cloaca. J Pediatr Surg 33(2):188–193 27. Singh JC, Jayanthi VR, Gopalakrishnan G (2008) Effect of hypospadias on sexual function and reproduction. Indian J Urol 24(2):249–252
781 28. Cortes D et al (1995) Cryptorchidism in boys with imperforate anus. J Pediatr Surg 30(4):631–635 29. Lee PA (2005) Fertility after cryptorchidism: epidemiology and other outcome studies. Urology 66(2):427–431 30. Rangel SJ, de Blaauw I (2010) Advances in pediatric colorectal surgical techniques. Semin Pediatr Surg 19(2):86–95 31. Pena A, Devries PA (1982) Posterior sagittal anorectoplasty: important technical considerations and new applications. J Pediatr Surg 17(6):796–811 32. Pena A et al (2003) Reoperative surgery for anorectal anomalies. Semin Pediatr Surg 12(2):118–123 33. Hong AR et al (2002) Urologic injuries associated with repair of anorectal malformations in male patients. J Pediatr Surg 37(3):339–344
123
ORIGINAL ARTICLE
The influence of anorectal malformations on fertility: a systematic review E. C. P. Huibregtse • J. M. Th. Draaisma • M. J. Hofmeester • K. Kluivers • I. A. L. M. van Rooij I. de Blaauw
•
Accepted: 18 June 2014 / Published online: 27 June 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose This systematic review aims to give an overview of available evidence concerning the influence of anorectal malformations (ARM) on fertility. Methods We conducted a search in PubMed, EMBASE and Cochrane Library conformed to the PRISMA standards. All studies reporting on fertility and ARM were included. Results 2,905 studies were identified. Based on title, abstract and full text, nine articles on 429 patients remained to answer the research question. Childbirth rate was the only reported outcome parameter to describe fertility. An overall childbirth rate of 27 % (range 0–57 %) was found. Mean age at time of study ranged from 23 to 35 years. There was no statistical significant difference in childbirth rate between female and male patients, based on seven
E. C. P. Huibregtse M. J. Hofmeester I. de Blaauw (&) Department of Pediatric Surgery, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands e-mail: [email protected] J. M. Th. Draaisma Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands K. Kluivers Department of Gynecology and Obstetrics, Radboud University Medical Center, Nijmegen, The Netherlands I. A. L. M. van Rooij Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands I. de Blaauw Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
studies (p = 0.45). Patients with a more complex type of ARM (imperforated anus without fistula, rectourethral bulbar and prostatic fistulas, rectobladderneck fistulas and cloacal malformations) had a lower childbirth rate compared to healthy controls, whereas in patients with a less complex ARM (rectoperineal or rectovestibular fistula) the childbirth rate was similar to healthy controls. Patients with a more complex type of ARM had a significant lower childbirth rate than patients with a less complex type of ARM (18 vs 47 %, respectively) (p = 0.0001). When further dividing these patients by gender, this difference was only seen in female patients (p = 0.04). Conclusion In patients with a more complex type of ARM a lower childbirth rate was found compared to healthy controls and patients with a less complex type of ARM. The latter was only seen in female patients. However, conclusions concerning fertility in ARM patients have to be taken with caution due to limited quality of the studies. Further investigation is recommended. Keywords Childbirth
Anorectal malformations Fertility
Introduction Anorectal malformations (ARM) comprise a wide spectrum of congenital conditions, characterized by an atresia or narrowing of the anorectal canal, with or without a fistula to neighboring organs. The malformations vary between minor defects with an excellent functional prognosis and complex defects with poor functional prognosis. ARM are associated in 40–70 % with other congenital malformations [1–4], such as those present in the VACTERL association (vertebral, anal, cardiac, trachea-
123
774
esophageal, renal, limb anomalies) or other genital and sacral malformations, but may also occur isolated [1–3]. The incidence of ARM is approximately 2–6 births per 10,000 births worldwide [5]. The initial therapy to obtain the function of the rectum is by surgery, which most often takes place in the first 2 years of life. Improvement in medical care has led to decreased morbidity and mortality, but complete functionality may still not be obtained, often leading to some degree of physical and social morbidity. The vast majority of patients with an ARM reaches adulthood nowadays. In this phase of life the influence of ARM on fertility plays a role. It is known that persons with all kinds of congenital malformations have lower childbirth rates than those without [6, 7]. The term fertility is defined as the capacity to conceive or to induce conception and to produce offspring. Fertility is influenced by many factors, including different topics ranging from the quality of the sperm cells and oocyts to the maintenance of a pregnancy. Fecundability or time-topregnancy is the best term to describe fertility. The reasons for impaired fertility are complex and multifactorial in ARM patients. These reasons may be related to the associated congenital malformations of the genital organ, spine and spinal cord, the surgery performed in the small pelvis, as well as the psychosocial problems caused by fecal incontinence, constipation, urinary incontinence and impaired sexual function. Although fertility is a very important issue in life, as has been indicated by parents’ societies [8], literature on this topic is not abundant. Therefore, it is relevant to juxtapose evidence and draw (preliminary) conclusions, which can be used to inform patients, parents and health care workers. The aim of our study was therefore to conduct a systematic review on the influence of ARM on fertility.
Methods Search strategy A literature search was performed in September 2013 in PubMed, the Cochrane Library and EMBASE to obtain all publications on studies that reported on ARM and fertility. The PubMed search used the Medical Subject Headings (MeSH) terms ‘‘Congenital abnormalities’’, ‘‘Anal Canal’’, ‘‘Anal’’, ‘‘Rectum’’, ‘‘Fistula’’, ‘‘Perineum’’, ‘‘Cloaca’’ and the text words ‘‘Anorectal malformation*’’, ‘‘Abnormalities’’, ‘‘Malformations’’, ‘‘Anus’’, ‘‘Anal’’, ‘‘Rectum’’, ‘‘Rectal’’, ‘‘Anorectal’’, ‘‘Fistula’’, ‘‘Perine*’’, ‘‘Vestibu*’’, ‘‘Rectoperineal’’, ‘‘Rectovestibular’’, ‘‘Rectourethral’’, ‘‘Rectovesical’’, ‘‘Rectobladderneck’’ and ‘‘Cloaca’’ combined with the MeSH terms ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Pregnancy rate’’, ‘‘Pregnancy’’, ‘‘Reproductive
123
Pediatr Surg Int (2014) 30:773–781
techniques’’, ‘‘Quality of life’’ and the text words ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Subfertility’’, ‘‘Time-to-pregnancy’’, ‘‘Pregnancy rate’’, ‘‘Pregnancy’’, ‘‘Fecundity’’, ‘‘Fecundability’’, ‘‘Reproductive techniques’’, ‘‘Quality of life’’ and ‘‘QoL’’. The Cochrane search used the same MeSH terms and text words. The EMBASE search used the EMTREE terms ‘‘Anorectal malformation’’, ‘‘Anus’’, ‘‘Rectum’’, ‘‘Anal canal’’, ‘‘Anus fistula’’, ‘‘Rectum fistula’’, ‘‘Rectovaginal fistula’’, ‘‘Perineum’’, ‘‘Fistula’’, ‘‘Cloaca’’ and the text words ‘‘Anorectal malformation*’’, ‘‘Abnormalities’’, ‘‘Malformation*’’, ‘‘Rectum’’, ‘‘Rectal’’, ‘‘Anus’’, ‘‘Anal’’, ‘‘Anal canal’’, ‘‘Fistula’’, ‘‘Perine*’’, ‘‘Vestibu*’’, ‘‘Rectoperineal’’, ‘‘Rectovestibular’’, ‘‘Rectourethral’’, ‘‘Rectovesical’’, ‘‘Rectobladderneck’’ and ‘‘Cloaca’’, combined with the EMTREE terms ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Reproduction’’, ‘‘Childbirth’’, ‘‘Conception’’ ‘‘Fertilization’’, ‘‘Parity’’, ‘‘Pregnancy’’, ‘‘Pregnancy outcome’’, ‘‘Pregnancy rate’’, ‘‘Infertility therapy’’, ‘‘Quality of life’’, ‘‘Birth rate’’ and the text words ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Subfertility’’, ‘‘Pregnancy outcome’’, ‘‘Pregnancy rate’’, ‘‘Birth rate’’, ‘‘Pregnancy’’, ‘‘Fecundity’’, ‘‘Fecundability’’, ‘‘Childbirth’’, ‘‘Infertility therapy’’, ‘‘Quality of life’’ and ‘‘Timeto-pregnancy’’. Limits were set to articles on humans. We conformed to the PRISMA statement to achieve the highest standard in reporting items for a systematic review [9, 10]. Eligibility criteria All studies that reported on any outcome measure regarding fertility in patients with an ARM were included. Studies on cloacal exstrophy were excluded, because of the complexity of the malformation with involvement of the bladder. Furthermore, case reports, studies without access to the full text and studies not written in English were excluded. The references of included studies were reviewed to include useful studies that might have been missed with the initial search (cross check). Study selection The study selection was dependent on four different steps; search strategy, study screening, study eligibility and study inclusion. They were all performed by one researcher (EH), under supervision of two medical experts (IdB, JD). Data extraction A predefined checklist was used. Data on study design, number and type of population, definition used to describe
Pediatr Surg Int (2014) 30:773–781
fertility, percentage of childbirth and described subtypes of ARM were collected. The Krickenbeck classification was used to define the subgroups of ARM patients, based on fistula type and the clinical use [11]. It was designed to make comparison of follow-up studies possible. However, the Wingspread classification was the most frequently used classification of ARM in literature. It classified different types of ARM in high, low and intermediate and contained a separate group for cloacal and rare malformations [12]. We therefore reclassified patients from the Wingspread classification, into the Krickenbeck classification as described in Table 1. ‘The more complex ARM group’ consisted of imperforated anus without fistula, rectourethral bulbar and prostatic fistulas, rectobladderneck fistulas and cloacal malformations, whereas ‘the less complex ARM group’ consisted of rectoperineal and rectovestibular fistulas.
Statistical analysis Descriptive analyses were performed. Childbirth rate was calculated by cumulating the number of patients with children of their own divided by the total patients included in the studies, when possible. 95 % confidence intervals were calculated around the mean. Using the Fisher’s exact test, we statistically tested differences in childbirth rate between males and females and between the less complex ARM group and the more complex ARM group.
775
Results The search resulted in 1,213 abstracts in PubMed, 23 abstracts in the Cochrane library and 1,669 abstracts in EMBASE. After exclusion of duplicates, 2,291 abstracts remained. Based on title, 2,145 abstracts were excluded. Based on abstract, another 111 abstracts were excluded. Reasons for exclusion were that articles were not reporting on ARM (n = 27), not reporting on fertility (n = 71), reporting on cloacal exstrophy (n = 5), concerning case reports (n = 18) or not written in English or no full text was available (n = 17). One study was included by cross checking references. Eventually, nine articles were left to answer our research question (Fig. 1). These nine studies were published between 1992 and 2013 in developed countries. Two out of the nine studies made a comparison with healthy controls [13, 14], the others studies were case series from a certain hospital or country. The total number of patients included ranged from 21 to 83 per study, in total 163 females and 120 males with ARM. The mean age at time of the study ranged from 23 to 35 years. All studies presented a differentiation in subtypes of ARM, but there was variation in reported classifications. Only one study used the Krickenbeck classification [8]. Childbirth rate was used to describe fertility in all studies and was defined as the percentage of persons who have children of their own. One study also mentioned the fertility rate (number of children per woman) [15]. Information on the number of patients who intended to conceive was available in two studies [16, 17]. Table 2 shows the
Table 1 Translation of the Wingspread classification to the Krickenbeck classification Type of classification
Krickenbeck classification
Wingspread classification High
Males
Intermediate
Rectoperineal fistula
Low
Cloaca
X
Rectourethral bulbar fistula
X
Rectourethral prostatic fistula
X
Rectobladderneck fistula
X
Imperforated anus without fistula
X
Complex and unusual defects Female
Rectoperineal fistula Rectovestibular fistula
X X
Cloaca with short common channel (\3 cm)
X (intermediate)
Cloaca with long common channel ([3 cm)
X (high)
Imperforated anus without fistula Complex and unusual defects
X
Cloacal exstrophy, covered cloacal exstrophy
X
Posterior cloaca
X
Associated to presacral mass Rectal atresia
X
123
776
Pediatr Surg Int (2014) 30:773–781
Fig. 1 Flow chart of study selection
study characteristics and Table 3 provides an overview of the results. Hundred and fifteen of the 429 patients with ARM had children of their own. This makes the overall childbirth rate 27 % [8, 13–20]. The two studies comparing patients with healthy controls showed that in patients with a less complex ARM, childbirth rate was similar, whereas in patients with a more complex ARM, childbirth rate was lower compared to controls [13, 14]. No differentiation was made between female and male patients. In seven out of nine studies, childbirth rate could be distracted by gender. There was no statistical significant difference in childbirth rate between female (19 %) and male patients (15 %) (p = 0.45). Childbirth in the more complex ARM group could be separated from the less complex ARM group, also in seven out of nine studies. This resulted in more childbirth in patients with a less complex ARM [57 of the 122 patients had children (47 %)] [13, 15, 19] than in patients with a more complex ARM [31 of the 176 patients had children (18 %)] (p = 0.0001) [14, 15, 17–20]. When dividing these patients by gender, a difference in childbirth rate in male patients with a less (10 %) and more (11 %) complex ARM was not found
123
(p = 1.00). However, female patients with a more complex ARM did have a lower childbirth rate than female patients with a less complex ARM (14 vs 39 %, respectively). This difference was statistical significant (p = 0.04). Cloacal malformation was the only subtypes of ARM that could be studied as a separate group [8, 15, 17–20]. Of the 79 included patients with a cloaca, 12 had offspring of their own (15 %). Mean age of the patients studied ranged from 23 to 26 years.
Discussion There is a lower childbirth rate in female patients with more complex ARM, compared to female patients with less complex ARM. This result may be explained by the fact that the incidence of genital malformations is significantly increasing with an increased complexity of the ARM [21– 23]. In patients with a rectoperineal fistula, genital malformations are rare (0–3 %) [21, 23], whereas genital malformations are by definition associated with patients with cloacal malformations, the most complex malformations in females. In these patients, 30 % present with a
Definition used for fertility
Childbirth rate
Childbirth rate
Childbirth rate
Childbirth rate
Childbirth rate
References, country
Rintala [13], Finland
Rintala [14], Finland
Schmidt [8], Germany
Hassink [18], The Netherlands
Davies [16], United Kingdom
Table 2 Study characteristics
Case series using questionnaires
Case series using questionnaires
Case series using personal interviews
Case-control study using questionnaires
Case-control study using questionnaires
Study design and method of data collection
7 (16 %)
11 (37 %)
30 M
5 (13 %) 44 F
3 (16 %)
19 F
3 (9 %)
32 M
39 M
5 (22 %)
Cases: 13 (39 %) Controls: 21 (60 %)
Controls: 45 (57 %)
Cases: 48 (57 %)
Patients with children of their own, no. (%)
23 F
25 M
8F
30 M
53 F
Number of patients
25.6 (SD 0.6)
26.0 (range 18.1–56.9)
23 (range 18-56)
35.3 (SD 4.8)
35.2 (SD 4.1)
Mean age at time of study (years)
8 Unknow
16 Low
6 High
3 Unknown
17 Low
15 Cloaca
9 High
High
4 Others 2 Unknown
0 Anal stenosis
3 Imperforated anus
6 Cloaca (1/6 got children)
10 Vestibular
5 Rectovesical
19 Rectouretral
6 Perineal
1 Rectobulbar fistula
1 Atresia Recti
2 Anal agenesis
2 Rectovesical fistula
19 Rectourethral fistula
1 Cloacal extrophy
4 Rectovaginal fisula 3 Cloaca
14 Anocutaneous fistula
16 Anal stenosis
4 N-type rectovestibular fistula
38 Anovestibular/vulvar fistula
3 Anocutaneous fistula
8 Anal stenosis
Type of ARM included
Pediatr Surg Int (2014) 30:773–781 777
123
123
Fertility rate (children/ woman). Childbirth rate
Childbirth rate
Childbirth rate
Childbirth rate (pregnancies)
Mantoo [15], France
Iwai [19], Japan
Hendren [20], Massachusetts, US
Warne [17], United Kingdom
Case series using hospital charts
Case series using hospital charts
Case series using questionnaires or personal interviews
Case series using questionnaires
Study design and method of data collection
F female, M male, X not reported, SD standard deviation
Definition used for fertility
References, country
Table 2 continued
21 F
0 (0 %)
6 (25 %)
0 (0 %)
18 M
24 F
4 (36 %)
4 (13 %)
31 M
11 F
6 (29 %)
Patients with children of their own, no. (%)
21 F
Number of patients
24
X
25.8
29.3
28 (SD 9)
Mean age at time of study (years)
Cloaca
Cloaca
3 Low (0/3 got children)
5 Intermediate (0/5 got children)
10 High (0/10 got children)
4 Low (2/4 got children)
4 Intermediate (0/4 got children)
3 High (2/3 got children)
1 Unknown (0/1 got children)
18 Low (2/18 got children)
12 High (2/12 got children)
1 Unknown (1/1 got children)
14 Low (5/14 got children)
6 High (0/6 got children)
Type of ARM included
778 Pediatr Surg Int (2014) 30:773–781
Pediatr Surg Int (2014) 30:773–781
779
Table 3 Childbirth rate in female and male patients with an ARM, divided by type of ARM % of childbirth
Type of ARM
Female patients
39 % (95 % CI: 16–61 %) [15, 19]
Male patients
10 % (95 % CI: 0–22 %) [15, 19]
Female and male patients
47 % (95 % CI: 38–56 %) [13, 15, 19]
Rectoperineal fistula
Rectovestibular fistula
Rectourethral bulbar fistula
Imperforated anus without fistula
Rectourethral prostatic fistula
Rectobladderneck fistula
11 % (95 % CI: 3–19 %) [15, 18, 19] 18 % (95 % CI: 12–23 %) [14, 15, 17–20]
hydrocolpos in the newborn period, which can lead to infection and vaginal scarring and reduce fertility [24]. Furthermore, 40 % of the cloaca patients will have a double Mu¨llerian system [24]. In another study, Warne et al. found a normal uterine anatomy in only 12 of the 41 patients with a cloaca (29 %), the other patients had a unicornuate, bicornuate, double or absent uterus. All Mu¨llerian abnormalities are associated with increased rates of pregnancy loss and preterm delivery [25]. 29 % of patients with a cloaca presented themselves for gynecological examination with an obstructed uterus due to stenosis of persistent urogenital sinus or cervical stenosis [26]. The inadequate outflow of menstrual blood can result in secondary damage, e.g., endometriosis, leading to further infertility [25, 26]. In male ARM patients, cryptorchidism and hypospadias are the most common genital malformations. In patients with hypospadia, no convincing evidence has been described for impaired fertility [27]. Cryptorchidism is described in 19 % of the boys with an ARM [28]. The higher the level of ARM, the higher the incidence [28]. Paternity rates have been found reduced in one-third of the patients with bilateral cryptorchidism [29]. If the incidence of bilateral cryptorchidism increases with an increased complexity of ARM, a decreased childbirth rate is expected in patients with more complex ARM. Apparently, genital malformations in male patients have less influence on childbirth rate than in female patients, because difference in childbirth rate between less and more complex ARM in male patients was not seen in our study. In spite of the evolution in surgical management of ARM [30], a second possible reason for a decreased childbirth rate is the possibility of iatrogenic damage. Since the mid-1980s, most patients are operated by the posterior
Cloaca
Overall
15 % (95 % CI: 7–23 %) [15, 17–20]
19 % (95 % CI: 13–25 %) [8, 15–20] 15 % (95 % CI: 9–21 %) [8, 15, 16, 18, 19] 28 % (95 % CI: 24–33 %) [8, 13–20]
sagittal anorectoplasty (PSARP). This technique allows a direct visualization of the anatomy of the muscle complex and nerves of the pelvic floor are spared as much as possible [31]. In female patients with less complex ARM, complications such as scarring of the perineum or vagina may occur, but are seldom described. Further damage to the reproductive tract is even less likely. Female patients with more complex ARM, such as cloacas, require a more challenging operation, with the risk of complications such as ischemic vaginal atresia, stenosis, recurrent fistulas or injury to the Mu¨llerian structures. In 30 % an additional abdominal approach will be necessary [32]. Long-term outcome data on the effect of these complications are, however, limited. In male patients, surgery of the most frequent rectoperineal fistula, does normally not involve the exposure of the reproductive tract and will therefore not affect fertility rates. Surgical exposure during PSARP performed in the other types of ARM is closer to the ejaculatory ducts, seminal vesicals, prostate, vas deference and nerves, responsible for sexual function. Iatrogenic complication rate of the reproductive tract was however only 1.7 % (10 out of 572 patients) in a study by Hong et al. [33]. Longterm outcomes regarding fertility in these patients are not available. Another reason for a decreased childbirth rate in more complex ARM may be related to psychosocial aspects of functional disorders such as fecal incontinence, constipation, urinary incontinence and impaired sexual function. These disorders are more often present in patients with more complex ARM. Psychosocial consequences may influence sexual activity and therefore indirectly have an impact on childbirth, but high quality studies are lacking on this subject.
123
780
Comparing results of fertility in patients with ARM remains difficult, because of the several limitations of the studies included. Fertility in ARM patients should be properly assessed and compared with a sex-, age- and social-matched control group. This adequate comparison was performed in only two studies. Small patient groups were used that could have caused the wide variation in childbirth rate. The mean age of patients in the cohorts of our review was relatively young, whereas the mean age to become a parent is usually higher. This obviously leads to a lower childbirth rate, independent from ARM. Another limitation of most studies is the use of childbirth rate as measurements for fertility. Questionnaires, personal interviews and hospital charts were used to count childbirth in patients with ARM, but only two studies reported the number of patients who had actively been trying to conceive [16, 17]. In a study by Davies et al. [16], 7 out of 44 women had children; the other women had not yet tried to conceive. In a study by Warne et al. [17], no children were born, but only four patients had tried to conceive. When childbirth was measured only in patients who tried to have children, the childbirth rate would probably have been much higher. At last, the type of ARM and additional anomalies should be well documented in all patients to relate this with the outcome of fertility. We recommend further research and studies with a preferable prospective design, with larger (multicenter) patient groups, higher mean age, well documented type of ARM and additional anomalies, time-to-pregnancy or fecundability as outcome measurement and healthy controls, matched for age, gender, and social status as comparison group.
Conclusion The aim of our study was to investigate the influence of ARM on fertility. The more complex ARM types seem to have a lower childbirth rate than healthy controls and patients with less complex ARM. The latter was only seen in female patients. Possible explanations for these findings could be found in the additional genital malformations often seen in female patients, iatrogenic damage of surgery and psychosocial consequences of ARM related to sexual activity. Overall, caution should be taken with interpreting these results. Due to limited quality of the studies, it remains difficult to make an unequivocal statement on fertility in patients with ARM and the underlying causes. Further investigation is recommended.
123
Pediatr Surg Int (2014) 30:773–781
References 1. Wijers CH et al (2013) Anorectal malformations and pregnancyrelated disorders: a registry-based case-control study in 17 European regions. BJOG 120(9):1066–1074 2. Stoll C et al (2007) Associated malformations in patients with anorectal anomalies. Eur J Med Genet 50(4):281–290 3. Cuschieri A, E.W. Group (2002) Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 110(2): 122–130 4. Hassink EA et al (1996) Additional congenital defects in anorectal malformations. Eur J Pediatr 155(6):477–482 5. International clearing house for birth defects surveillance and research (2011). In: Annual report: with data for 2009. http://www. icbdsr.org/filebank/documents/ar2005/Report2011.pdf. Accessed 24 August 2012 6. Skjaerven R, Wilcox AJ, Lie RT (1999) A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children. N Engl J Med 340(14):1057–1062 7. Lie RT, Wilcox AJ, Skjaerven R (2001) Survival and reproduction among males with birth defects and risk of recurrence in their children. JAMA 285(6):755–760 8. Schmidt D et al (2012) Sexual function in adults with anorectal malformation: psychosocial adaptation. German Network for Congenital Uro-REctal Malformations (CURE-Net). Pediatr Surg Int 28(8):789–792 9. Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–e34 10. Moher D et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341 11. Holschneider A et al (2005) Preliminary report on the International Conference for the Development of Standards for the treatment of anorectal malformations. J Pediatr Surg 40(10): 1521–1526 12. Anorectal malformations in children: update 1988 (1988) Birth Defects Orig Artic Ser 24(4):1–604 13. Rintala R, Mildh L, Lindahl H (1992) Fecal continence and quality of life in adult patients with an operated low anorectal malformation. J Pediatr Surg 27(7):902–905 14. Rintala R, Mildh L, Lindahl H (1994) Fecal continence and quality of life for adult patients with an operated high or intermediate anorectal malformation. J Pediatr Surg 29(6):777–780 15. Mantoo S et al (2013) The impact of anorectal malformations on anorectal function and social integration in adulthood: report from a national database. Colorectal Dis 15(6):e330–e335 16. Davies MC et al (2010) Anorectal malformations: what happens in adulthood? BJU Int 106(3):398–404 17. Warne SA et al (2003) Long-term gynecological outcome of patients with persistent cloaca. J Urol 170(4 Pt 2):1493–1496 18. Hassink EA et al (1994) Quality of life after operatively corrected high anorectal malformation: a long-term follow-up study of patients aged 18 years and older. J Pediatr Surg 29(6):773–776 19. Iwai N et al (2007) Social quality of life for adult patients with anorectal malformations. J Pediatr Surg 42(2):313–317 20. Hendren WH (1998) Cloaca, the most severe degree of imperforate anus: experience with 195 cases. Ann Surg 228(3):331–346 21. Metts JC 3rd et al (1997) Genital malformations and coexistent urinary tract or spinal anomalies in patients with imperforate anus. J Urol 158(3 Pt 2):1298–1300
Pediatr Surg Int (2014) 30:773–781 22. Nah SA et al (2012) Anomalies associated with anorectal malformations according to the Krickenbeck anatomic classification. J Pediatr Surg 47(12):2273–2278 23. Rich MA, Brock WA, Pena A (1988) Spectrum of genitourinary malformations in patients with imperforate anus. Pediatr Surg Int 3:110–113 24. Levitt MA, Pena A (2010) Cloacal malformations: lessons learned from 490 cases. Semin Pediatr Surg 19(2):128–138 25. Rackow BW, Arici A (2007) Reproductive performance of women with mullerian anomalies. Curr Opin Obstet Gynecol 19(3):229–237 26. Levitt MA, Stein DM, Pena A (1998) Gynecologic concerns in the treatment of teenagers with cloaca. J Pediatr Surg 33(2):188–193 27. Singh JC, Jayanthi VR, Gopalakrishnan G (2008) Effect of hypospadias on sexual function and reproduction. Indian J Urol 24(2):249–252
781 28. Cortes D et al (1995) Cryptorchidism in boys with imperforate anus. J Pediatr Surg 30(4):631–635 29. Lee PA (2005) Fertility after cryptorchidism: epidemiology and other outcome studies. Urology 66(2):427–431 30. Rangel SJ, de Blaauw I (2010) Advances in pediatric colorectal surgical techniques. Semin Pediatr Surg 19(2):86–95 31. Pena A, Devries PA (1982) Posterior sagittal anorectoplasty: important technical considerations and new applications. J Pediatr Surg 17(6):796–811 32. Pena A et al (2003) Reoperative surgery for anorectal anomalies. Semin Pediatr Surg 12(2):118–123 33. Hong AR et al (2002) Urologic injuries associated with repair of anorectal malformations in male patients. J Pediatr Surg 37(3):339–344
123
