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Culture Documents
DOI 10.1007/s00383-014-3535-5
ORIGINAL ARTICLE
I. de Blaauw
J. M. Th. Draaisma
Department of Pediatrics, Radboud University Medical Center,
Introduction
Nijmegen, The Netherlands
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esophageal, renal, limb anomalies) or other genital and techniques’’, ‘‘Quality of life’’ and the text words ‘‘Fertil-
sacral malformations, but may also occur isolated [1–3]. ity’’, ‘‘Infertility’’, ‘‘Subfertility’’, ‘‘Time-to-pregnancy’’,
The incidence of ARM is approximately 2–6 births per ‘‘Pregnancy rate’’, ‘‘Pregnancy’’, ‘‘Fecundity’’, ‘‘Fecunda-
10,000 births worldwide [5]. bility’’, ‘‘Reproductive techniques’’, ‘‘Quality of life’’ and
The initial therapy to obtain the function of the rectum is ‘‘QoL’’.
by surgery, which most often takes place in the first 2 years The Cochrane search used the same MeSH terms and
of life. Improvement in medical care has led to decreased text words.
morbidity and mortality, but complete functionality may The EMBASE search used the EMTREE terms ‘‘Ano-
still not be obtained, often leading to some degree of rectal malformation’’, ‘‘Anus’’, ‘‘Rectum’’, ‘‘Anal canal’’,
physical and social morbidity. The vast majority of patients ‘‘Anus fistula’’, ‘‘Rectum fistula’’, ‘‘Rectovaginal fistula’’,
with an ARM reaches adulthood nowadays. In this phase of ‘‘Perineum’’, ‘‘Fistula’’, ‘‘Cloaca’’ and the text words
life the influence of ARM on fertility plays a role. It is ‘‘Anorectal malformation*’’, ‘‘Abnormalities’’, ‘‘Malfor-
known that persons with all kinds of congenital malfor- mation*’’, ‘‘Rectum’’, ‘‘Rectal’’, ‘‘Anus’’, ‘‘Anal’’, ‘‘Anal
mations have lower childbirth rates than those without [6, canal’’, ‘‘Fistula’’, ‘‘Perine*’’, ‘‘Vestibu*’’, ‘‘Rectoperi-
7]. The term fertility is defined as the capacity to conceive neal’’, ‘‘Rectovestibular’’, ‘‘Rectourethral’’, ‘‘Rectovesi-
or to induce conception and to produce offspring. Fertility cal’’, ‘‘Rectobladderneck’’ and ‘‘Cloaca’’, combined with
is influenced by many factors, including different topics the EMTREE terms ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Reproduc-
ranging from the quality of the sperm cells and oocyts to tion’’, ‘‘Childbirth’’, ‘‘Conception’’ ‘‘Fertilization’’, ‘‘Par-
the maintenance of a pregnancy. Fecundability or time-to- ity’’, ‘‘Pregnancy’’, ‘‘Pregnancy outcome’’, ‘‘Pregnancy
pregnancy is the best term to describe fertility. rate’’, ‘‘Infertility therapy’’, ‘‘Quality of life’’, ‘‘Birth rate’’
The reasons for impaired fertility are complex and and the text words ‘‘Fertility’’, ‘‘Infertility’’, ‘‘Subfertility’’,
multifactorial in ARM patients. These reasons may be ‘‘Pregnancy outcome’’, ‘‘Pregnancy rate’’, ‘‘Birth rate’’,
related to the associated congenital malformations of the ‘‘Pregnancy’’, ‘‘Fecundity’’, ‘‘Fecundability’’, ‘‘Child-
genital organ, spine and spinal cord, the surgery performed birth’’, ‘‘Infertility therapy’’, ‘‘Quality of life’’ and ‘‘Time-
in the small pelvis, as well as the psychosocial problems to-pregnancy’’.
caused by fecal incontinence, constipation, urinary incon- Limits were set to articles on humans.
tinence and impaired sexual function. We conformed to the PRISMA statement to achieve the
Although fertility is a very important issue in life, as has highest standard in reporting items for a systematic review
been indicated by parents’ societies [8], literature on this [9, 10].
topic is not abundant. Therefore, it is relevant to juxtapose
evidence and draw (preliminary) conclusions, which can be Eligibility criteria
used to inform patients, parents and health care workers.
The aim of our study was therefore to conduct a systematic All studies that reported on any outcome measure regard-
review on the influence of ARM on fertility. ing 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
Methods bladder. Furthermore, case reports, studies without access
to the full text and studies not written in English were
Search strategy excluded. The references of included studies were
reviewed to include useful studies that might have been
A literature search was performed in September 2013 in missed with the initial search (cross check).
PubMed, the Cochrane Library and EMBASE to obtain all
publications on studies that reported on ARM and fertility. Study selection
The PubMed search used the Medical Subject Headings
(MeSH) terms ‘‘Congenital abnormalities’’, ‘‘Anal Canal’’, The study selection was dependent on four different steps;
‘‘Anal’’, ‘‘Rectum’’, ‘‘Fistula’’, ‘‘Perineum’’, ‘‘Cloaca’’ and search strategy, study screening, study eligibility and study
the text words ‘‘Anorectal malformation*’’, ‘‘Abnormali- inclusion. They were all performed by one researcher (EH),
ties’’, ‘‘Malformations’’, ‘‘Anus’’, ‘‘Anal’’, ‘‘Rectum’’, under supervision of two medical experts (IdB, JD).
‘‘Rectal’’, ‘‘Anorectal’’, ‘‘Fistula’’, ‘‘Perine*’’, ‘‘Vestibu*’’,
‘‘Rectoperineal’’, ‘‘Rectovestibular’’, ‘‘Rectourethral’’, Data extraction
‘‘Rectovesical’’, ‘‘Rectobladderneck’’ and ‘‘Cloaca’’ com-
bined with the MeSH terms ‘‘Fertility’’, ‘‘Infertility’’, A predefined checklist was used. Data on study design,
‘‘Pregnancy rate’’, ‘‘Pregnancy’’, ‘‘Reproductive number and type of population, definition used to describe
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study characteristics and Table 3 provides an overview of (p = 1.00). However, female patients with a more complex
the results. ARM did have a lower childbirth rate than female patients
Hundred and fifteen of the 429 patients with ARM had with a less complex ARM (14 vs 39 %, respectively). This
children of their own. This makes the overall childbirth rate difference was statistical significant (p = 0.04).
27 % [8, 13–20]. The two studies comparing patients with Cloacal malformation was the only subtypes of ARM
healthy controls showed that in patients with a less com- that could be studied as a separate group [8, 15, 17–20]. Of
plex ARM, childbirth rate was similar, whereas in patients the 79 included patients with a cloaca, 12 had offspring of
with a more complex ARM, childbirth rate was lower their own (15 %). Mean age of the patients studied ranged
compared to controls [13, 14]. No differentiation was made from 23 to 26 years.
between female and male patients.
In seven out of nine studies, childbirth rate could be
distracted by gender. There was no statistical significant Discussion
difference in childbirth rate between female (19 %) and
male patients (15 %) (p = 0.45). Childbirth in the more There is a lower childbirth rate in female patients with
complex ARM group could be separated from the less more complex ARM, compared to female patients with less
complex ARM group, also in seven out of nine studies. complex ARM. This result may be explained by the fact
This resulted in more childbirth in patients with a less that the incidence of genital malformations is significantly
complex ARM [57 of the 122 patients had children (47 %)] increasing with an increased complexity of the ARM [21–
[13, 15, 19] than in patients with a more complex ARM [31 23]. In patients with a rectoperineal fistula, genital mal-
of the 176 patients had children (18 %)] (p = 0.0001) [14, formations are rare (0–3 %) [21, 23], whereas genital
15, 17–20]. When dividing these patients by gender, a malformations are by definition associated with patients
difference in childbirth rate in male patients with a less with cloacal malformations, the most complex malforma-
(10 %) and more (11 %) complex ARM was not found tions in females. In these patients, 30 % present with a
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Table 2 Study characteristics
References, country Definition used for fertility Study design and method of data Number of Patients with children of Mean age at time of Type of ARM included
collection patients their own, no. (%) study (years)
Rintala [13], Childbirth rate Case-control study using 53 F Cases: 48 (57 %) 35.2 (SD 4.1) 8 Anal stenosis
Finland questionnaires Controls: 45 (57 %) 3 Anocutaneous fistula
38 Anovestibular/vulvar fistula
4 N-type rectovestibular fistula
30 M 16 Anal stenosis
14 Anocutaneous fistula
Pediatr Surg Int (2014) 30:773–781
Rintala [14], Childbirth rate Case-control study using 8F Cases: 13 (39 %) 35.3 (SD 4.8) 4 Rectovaginal fisula
Finland questionnaires Controls: 21 (60 %) 3 Cloaca
1 Cloacal extrophy
25 M 19 Rectourethral fistula
2 Rectovesical fistula
2 Anal agenesis
1 Atresia Recti
1 Rectobulbar fistula
Schmidt [8], Childbirth rate Case series using personal 23 F 5 (22 %) 23 (range 18-56) 6 Perineal
Germany interviews 32 M 3 (9 %) 19 Rectouretral
5 Rectovesical
10 Vestibular
6 Cloaca (1/6 got children)
3 Imperforated anus
0 Anal stenosis
4 Others
2 Unknown
Hassink [18], The Childbirth rate Case series using questionnaires 19 F 3 (16 %) 26.0 (range High
Netherlands 39 M 5 (13 %) 18.1–56.9)
Davies [16], United Childbirth rate Case series using questionnaires 44 F 7 (16 %) 25.6 (SD 0.6) 9 High
Kingdom 15 Cloaca
17 Low
3 Unknown
30 M 11 (37 %) 6 High
16 Low
8 Unknow
777
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Table 2 continued
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References, country Definition used for fertility Study design and method of data Number of Patients with children of Mean age at time of Type of ARM included
collection patients their own, no. (%) study (years)
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Mantoo [15], Fertility rate (children/ Case series using questionnaires 21 F 6 (29 %) 28 (SD 9) 6 High (0/6 got children)
France woman). Childbirth rate 14 Low (5/14 got children)
1 Unknown (1/1 got children)
31 M 4 (13 %) 12 High (2/12 got children)
18 Low (2/18 got children)
1 Unknown (0/1 got children)
Iwai [19], Japan Childbirth rate Case series using questionnaires 11 F 4 (36 %) 29.3 3 High (2/3 got children)
or personal interviews 4 Intermediate (0/4 got children)
4 Low (2/4 got children)
18 M 0 (0 %) 25.8 10 High (0/10 got children)
5 Intermediate (0/5 got children)
3 Low (0/3 got children)
Hendren [20], Childbirth rate Case series using hospital charts 24 F 6 (25 %) X Cloaca
Massachusetts,
US
Warne [17], United Childbirth rate (pregnan- Case series using hospital charts 21 F 0 (0 %) 24 Cloaca
Kingdom cies)
F female, M male, X not reported, SD standard deviation
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 Type of ARM
childbirth
Rectoperineal Recto- Rectourethral Imperforated Rectourethral Rectobladder- Cloaca Overall
fistula vestibular bulbar fistula anus without prostatic neck fistula
fistula fistula fistula
hydrocolpos in the newborn period, which can lead to sagittal anorectoplasty (PSARP). This technique allows a
infection and vaginal scarring and reduce fertility [24]. direct visualization of the anatomy of the muscle complex
Furthermore, 40 % of the cloaca patients will have a and nerves of the pelvic floor are spared as much as pos-
double Müllerian system [24]. In another study, Warne sible [31]. In female patients with less complex ARM,
et al. found a normal uterine anatomy in only 12 of the 41 complications such as scarring of the perineum or vagina
patients with a cloaca (29 %), the other patients had a may occur, but are seldom described. Further damage to
unicornuate, bicornuate, double or absent uterus. All the reproductive tract is even less likely. Female patients
Müllerian abnormalities are associated with increased rates with more complex ARM, such as cloacas, require a more
of pregnancy loss and preterm delivery [25]. 29 % of challenging operation, with the risk of complications such
patients with a cloaca presented themselves for gyneco- as ischemic vaginal atresia, stenosis, recurrent fistulas or
logical examination with an obstructed uterus due to ste- injury to the Müllerian structures. In 30 % an additional
nosis of persistent urogenital sinus or cervical stenosis [26]. abdominal approach will be necessary [32]. Long-term
The inadequate outflow of menstrual blood can result in outcome data on the effect of these complications are,
secondary damage, e.g., endometriosis, leading to further however, limited.
infertility [25, 26]. In male patients, surgery of the most frequent recto-
In male ARM patients, cryptorchidism and hypospadias perineal fistula, does normally not involve the exposure of
are the most common genital malformations. In patients the reproductive tract and will therefore not affect fertility
with hypospadia, no convincing evidence has been rates. Surgical exposure during PSARP performed in the
described for impaired fertility [27]. Cryptorchidism is other types of ARM is closer to the ejaculatory ducts,
described in 19 % of the boys with an ARM [28]. The seminal vesicals, prostate, vas deference and nerves,
higher the level of ARM, the higher the incidence [28]. responsible for sexual function. Iatrogenic complication
Paternity rates have been found reduced in one-third of the rate of the reproductive tract was however only 1.7 % (10
patients with bilateral cryptorchidism [29]. If the incidence out of 572 patients) in a study by Hong et al. [33]. Long-
of bilateral cryptorchidism increases with an increased term outcomes regarding fertility in these patients are not
complexity of ARM, a decreased childbirth rate is expected available.
in patients with more complex ARM. Apparently, genital Another reason for a decreased childbirth rate in more
malformations in male patients have less influence on complex ARM may be related to psychosocial aspects of
childbirth rate than in female patients, because difference functional disorders such as fecal incontinence, constipa-
in childbirth rate between less and more complex ARM in tion, urinary incontinence and impaired sexual function.
male patients was not seen in our study. These disorders are more often present in patients with
In spite of the evolution in surgical management of more complex ARM. Psychosocial consequences may
ARM [30], a second possible reason for a decreased influence sexual activity and therefore indirectly have an
childbirth rate is the possibility of iatrogenic damage. Since impact on childbirth, but high quality studies are lacking on
the mid-1980s, most patients are operated by the posterior this subject.
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22. Nah SA et al (2012) Anomalies associated with anorectal mal- 28. Cortes D et al (1995) Cryptorchidism in boys with imperforate
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J Pediatr Surg 47(12):2273–2278 29. Lee PA (2005) Fertility after cryptorchidism: epidemiology and
23. Rich MA, Brock WA, Pena A (1988) Spectrum of genitourinary other outcome studies. Urology 66(2):427–431
malformations in patients with imperforate anus. Pediatr Surg Int 30. Rangel SJ, de Blaauw I (2010) Advances in pediatric colorectal
3:110–113 surgical techniques. Semin Pediatr Surg 19(2):86–95
24. Levitt MA, Pena A (2010) Cloacal malformations: lessons 31. Pena A, Devries PA (1982) Posterior sagittal anorectoplasty:
learned from 490 cases. Semin Pediatr Surg 19(2):128–138 important technical considerations and new applications. J Pedi-
25. Rackow BW, Arici A (2007) Reproductive performance of atr Surg 17(6):796–811
women with mullerian anomalies. Curr Opin Obstet Gynecol 32. Pena A et al (2003) Reoperative surgery for anorectal anomalies.
19(3):229–237 Semin Pediatr Surg 12(2):118–123
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treatment of teenagers with cloaca. J Pediatr Surg 33(2):188–193 anorectal malformations in male patients. J Pediatr Surg
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