Introduction

Congenital anorectal malformations present with a spectrum of severity and complexity and are associated with various other congenital malformations [1,2,3]. Female patients born with anorectal malformations (ARM) have a higher incidence of Mullerian anomalies. Uterine and vaginal duplication is reported in up to 60% of patients with cloacal anomalies and may require surgical intervention early in life, e.g. drainage of hydrocolpos [4].

Prior studies report spontaneous conception and pregnancy in patients with ARM, however most delivered by cesarean section [5]. Huibregtse et al. performed a systematic literature review of the influence of ARM on fertility which included nine articles and a total of 429 patients. This review concluded that female patients with a more complex type of ARM had a lower childbirth rate when compared to healthy references or patients with a less complex type of ARM [6]. This data is supported by a recent study by Reppucci et al. In this cohort, there were no pregnancies reported in patients with ARM and partial vaginal replacement with bowel [7]. Fertility is impacted by many factors; Mullerian anomalies for example has been found in up to 25% of females with a history of miscarriage and infertility [8]. In patients with ARM, fertility may be impaired by the complexity of the anomaly, extensive surgical history, other medical comorbidities, as well as associated Mullerian anomalies. Assisted reproduction and/or alternative family building may be needed in complex malformations, especially in those who have a partial neovagina replacement with bowel [5].

Prior research has shown that female infertility impairs quality of life [9]. Outcome data regarding fertility concerns and the influence on quality of life in patients with ARM is lacking. Because female patients with a history of surgical correction of a congenital colorectal condition have higher rates of depression and anxiety [10], we hypothesize that patients with history of ARM and fertility concerns may have impaired quality of life. The purpose of this study is to report fertility concerns, compare fertility quality of life scores to published reference scores, and describe pregnancy outcomes in female patients with ARM.

Methods

This was a cross sectional study of patients assigned female at birth with an ARM (ARM with perineal, vestibular or vaginal fistula, Cloaca and complex ARM), who were registered in our Adult Colorectal Research Registry. Patients between the ages of 18–80 years of age were contacted to participate in the study. Those who agreed to participate were then sent an email with the link to Research Electronic Data Capture (REDCap) questionnaires which included reproductive health surveys assessing fertility concerns and fertility problems, as well as the Fertility Quality of Life survey (FertiQoL) [9, 11]. Data collected included basic demographics, diagnosis of the malformation, operative treatment, gynecological history, as well as obstetrical history including fertility treatment. Participants who completed the study between November 2021 and August 2022 were included.

The FertiQoL is an internationally validated survey assessing the quality of life in patients who experience fertility problems. It was created by two reproductive medical societies (European Society of Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM) in association with Merck-Serono S.A. [9, 12]. The questionnaire was validated with over 2000 men and women experiencing fertility problems in USA, Australia/New Zealand, Canada and UK and later translated into 20 different languages. The survey consists of 36 items that assess core (24 items) and treatment-related QoL (10 items) and overall life and physical health (2 items). The 24 core items subdivided into emotional, mind–body (i.e. cognitive and physical), relational and social domains. Each question was rated from 0 to 4 with higher scores indicating better QoL.

Study data were collected and managed using REDCap electronic data capture tool [11]. Descriptive statistics are reported as median (Q1, Q3) for numeric variables and as frequency (%) for categorical variables. One-sample Wilcoxon tests were used to compare FertiQoL scores to the survey validation population [9, 12]. Treatment-realted scores for FertiQoL were assessed in only three patients, since those underwent fertility treatment. Due to this limited sample size, no Wilcoxon tests were performed for the treatment scores and thus no p-values are reported. Statistical analyses were performed using R Studio (version 4.1.2). P-values < 0.05 were considered statistically significant. IRB approval was obtained from the Colorado Multiple Institutional Review Board (COMIRB) #21-3154 and #19-1050.

Results

A total of 97 females were invited to participate in the study, of which 78 responded (80.4% response rate). Sixty-four patients with ARM met inclusion criteria with age ranging from 22 to 80 years with an overall median age of 32 years. Sixty-two identified as female and two identified as non-binary. Over half of respondents had a diagnosis of cloaca (62.5%), which included 39 patients with cloaca and one with posterior cloaca. Other ARM (29.7%) included: three recto-perineal, 14 recto-vestibular, one recto-vaginal or no fistula. Those with complex malformations (7.8%) included: one covered cloacal exstrophy, one cloacal exstrophy, one cloacal exstrophy variant, one complex anorectal malformation and one complex anorectal malformation with duplication of the pelvis and external genitalia (Table 1).

Table 1 ARM diagnosis and fertility concerns and problems
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Fertility concerns

Twenty-six patients (40.6%) reported concerns about fertility (Table 1 and Fig. 1). Ages ranged from 21 to 47 years with a median age of 31 years. The majority were patients born with a cloaca (21 patients). Fertility concerns were highest in those who have not tried yet to conceive (26.6%) followed by females who successfully got pregnant in the past (12.5%) (Fig. 1). Eleven (17%) were seen by a fertility specialist including four who have not tried to conceive yet.

Fig. 1
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Pregnancy attempts and fertility concerns in patients with ARM

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Fertility problems

Sixteen participants (25%) reported fertility problems (Table 1), which included: Mullerian abnormalities in 11, blocked or damaged tubes in six, ovulation problems in two, diminished ovarian reserve in two (age 43 and 26), and unexplained infertility in two. For example, one female with cloaca successfully gave birth to twins with donor egg and IVF after years of trying to conceive with one spontaneous pregnancy that ended in miscarriage. Another patient with cloaca had her biological children through a gestational carrier.

Interestingly none of the patients without fertility concerns reported fertility problems, although four had a hysterectomy or resection of Mullerian structures (bilateral hemi-uterus resection) with or without oophorectomy.

Pregnancy outcomes

Forty percent (n = 26) of the overall population tried to conceive, with the majority (34.4%) reporting pregnancy ending in either miscarriage or delivery (Table 2 and Fig. 1). There were 18 females with 26 pregnancies resulting in 28 live births (overall ratio 1.6 child/patient) and 11 females with 18 pregnancies resulting in miscarriage (MC) (overall ratio 1.6MC/patient). The child/patient ratio was higher (1.8 vs. 1.5) and the miscarriage/woman ratio (1.2 vs. 2.2) lower, in the patient population with fertility concerns compared to those without. Six females reported they underwent assisted reproductive technologies (IVF, donor egg, medical stimulated ovulation, surrogacy or gestational).

Table 2 Fertility concerns and reported pregnancy and miscarriage rate in patients with anorectal malformation
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The vast majority of patients delivered via cesarean section (n = 24, 92%) Indications for cesarean section included history of ARM (n = 23), malposition of the fetus (n = 6), fetal distress (n = 1), and extensive urologic surgical history (n = 1). Mode of delivery was unknown in two patients. Fifteen pregnancies were born at term and seven were preterm between 33 and 36 weeks gestational age. Gestational age data was missing in four patients.

FertiQoL in patients with fertility concerns

Females who reported fertility concerns, were further assessed with the FertiQoL instrument (Tables 3 and 4). In comparison to published reference scores for female and male patients who actively seek treatment at a fertility clinic, patients with cloaca, ARM and complex malformation scored significantly higher, meaning having better QoL (Table 5). Patients with complex malformations had the lowest scores [9, 12]. Interestingly there was no statistically significant difference in the domain relationship, which assesses the impact of fertility issues on interpersonal interactions in our patient cohort compared to published reference scores. In our patient cohort, three actively underwent fertility treatment. For the subscore of fertility treatment, they scored lower than the reference scores. No statistical analysis was performed due to the small sample size.

Table 3 Demographics only of the patients with fertility concerns, who underwent assessment with FertiQoL questionnaire
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Table 4 Scaled FertiQoL scores by diagnosis
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Table 5 Scaled FertiQoL One-sample Wilcoxon Test Results
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Discussion

Fertility concerns, pregnancy outcomes and Fertility Quality of Life of female patients of the Adult Colorectal Research Registry with ARM are presented. Females born with ARM have risk factors for infertility, including Mullerian anomalies and adhesive disease or iatrogenic damage to reproductive structures from complex reconstructive surgeries [13]. Consistent with existing literature, patients with anorectal malformations can achieve pregnancy, however assisted reproduction and alternative family building may be needed in those with complex anomalies who desire parenthood. Almost all patients in this cohort delivered by cesarean-section which is consistent with prior report by Chan et al. [5]. Participants with recto-perineal and recto-vestibular fistulas reported a recommendation to deliver by cesarean-section due to concern that vaginal birth could pose a risk to the PSARP repair. Although these risks have not been established, most experts agree that these patients are candidates for a vaginal delivery if they have an adequate perineal body [14].

In this cohort, 40% of the patients reported fertility concerns, with less than half of them being seen by a fertility specialist and approximately 9% undergoing fertility treatment. This study highlights several important aspects in the management of patients born with ARM. Multidisciplinary teams should include a gynecologist or fertility specialist to address fertility potential and concerns, if future parenthood is desired. Early education about the potential impact of congenital malformations on fertility is especially important for continuity and transition of care.

Patients without fertility concerns did not report any fertility problems, though interestingly these patients also had Mullerian anomalies and extensive surgical histories. For example, patients who had a hysterectomy, resection of Mullerian structures with oophorectomy, or who had fertility treatment with IVF or surrogacy, reported no fertility issues or concerns. This survey did not assess desire for fertility. It is unclear if those without fertility concerns want future fertility or parenthood. Future studies should explore desire for parenthood, fertility intentions and understanding in how medical and surgical history affects fertility. Regardless of family planning intentions, patients and families should be fully informed of the impact ARM diagnosis, treatment, and associated anomalies has on fertility.

Among patients with fertility concerns, FertiQoL score in patients with ARM was higher when compared to a reference population of male and females experiencing fertility problems. FertiQoL was developed for patients seeking fertility treatment. In this study, FertiQoL was administered to all patients with fertility concerns including those with and without fertility problems seeking treatment. This study cohort is quite different than the reference population which may account for higher FertiQoL scores. Prior research has shown that higher scores are associated with secondary fertility. More research is needed to validate and assess the survey in patients at risk for infertility or with fertility concerns.

Conclusion

Patients with ARM may have concerns about their fertility. It is imperative that providers are aware of these concerns and consider proactive counselling. Discussion of the patient’s diagnosis, past surgical interventions and its impact on future fertility is necessary. Patients with ARM who desire parenthood, especially those with Mullerian anomalies and complex anatomy, should be referred to a fertility specialist. Early interventions to optimize and preserve fertility should also be explored.