Introduction

Intersex is an umbrella term used to refer to individuals born with physical or biological sex characteristics (including sexual anatomy, reproductive organs and/or chromosomal patterns) that do not fit normative definitions of male or female bodies [1]. These congenital variations in sex characteristics, also known as differences/disorders of sex development (DSDs), are a large, heterogeneous group of reproductive, urogenital, chromosomal and/or hormonal congenital conditions, with the set of diagnoses lying within these umbrella terms varying across different settings and disciplines [2, 3]. Some of these variations may be visible and identifiable at birth, while others may not be recognized until later in childhood, puberty and/or adulthood [1].

Many congenital variations in sex characteristics pose no threat to physical health, while others may necessitate medical or surgical intervention (i.e., to facilitate excretion or urination). However, standard surgical practice for decades has involved using a variety of elective (i.e., non-urgent) surgical procedures to attempt to ‘normalize’ ‘atypical’ traits in people with congenital variations in sex characteristics, striving for cosmetic, functional and anatomical outcomes that align more with those associated with ‘typical’ male or female bodies [4], referred to in this manuscript as “sex-normalising” interventions. These procedures frequently take place in infancy or early childhood, due in part to pervasive beliefs that early intervention will facilitate better psychological and/or physiological development, and alleviate anticipated personal and parental stress associated with the congenital variation in sex characteristics [5–8]. Treatment options may also involve hormonal therapy, mechanical procedures (e.g., neovaginal dilations), or surgical, hormonal, and mechanical interventions which take place in adolescence, all of which are outside the scope of this review.

The continued conduct of “sex-normalising” surgical interventions in infancy or early childhood is supported by clinical guidance such as the 2006 Consensus Statement on Management of Intersex Disorders, a statement that attempted to create recommendations for the long-term management, evaluation of, and future research into, congenital variations in sex characteristics [9]. This is despite a noted lack of evidence regarding the physical, mental, and social outcomes of infants with congenital variations in sex characteristics who have undergone such interventions, with an extant evidence-base primarily consisting of short case reports and cohort data with small sample sizes [2, 4].

Evidence on patient preference for infant surgical intervention, despite still being used as a rationale for procedures, is also inconsistent. Although some patients retrospectively express a clear preference for, and satisfaction with, early surgical intervention [10–12], others who have undergone these surgeries share dissatisfaction with long-term outcomes, citing resultant distress and trauma associated with subsequent gender identity, compromised sexual function and pleasure, dissatisfaction with genital appearance and a reflective distress surrounding their compromised autonomy for interventions practiced before they were able to articulate consent for the procedure [13–23].

Human rights experts have recently raised serious concerns about the conduct of elective, irreversible, “sex-normalising” surgical interventions carried out in infancy and childhood. In October 2016, multiple UN human rights monitoring and accountability mechanisms (The international human rights treaty bodies and special procedures behind this joint statement were the UN Committee on the Rights of the Child, UN Committee against Torture, UN Committee on the Rights of People with Disabilities, UN Sub-Committee on Prevention of Torture and other Cruel, Inhuman or Degrading Treatment or Punishment, UN Special Rapporteur on torture and other cruel, inhuman or degrading treatment or punishment, UN Special Rapporteur on the right of everyone to the highest attainable standard of health, UN Special Rapporteur on violence against women, its causes and consequences, Special Representative of the UN Secretary-General on Violence against Children, African Commission on Human and Peoples’ Rights, Council of Europe Commissioner for Human Rights and the Inter-American Commission on Human Rights.) issued a joint statement highlighting the human rights violations associated with ‘medically unnecessary surgeries […] in an attempt to forcibly change [intersex infants’, children’s and adolescents’] appearance to be in line with societal expectations about female and male bodies’ and called on governments to ’prohibit harmful medical practices on intersex children, including unnecessary surgery and treatment without their informed consent’ [24]. Following this, several UN human rights treaty bodies, including the UN Committee on the Rights of the Child [25], as well as the World Health Organization (WHO) [26], have provided further advice, speaking out against medically unnecessary surgical interventions for infants with congenital variations in sex characteristics on the grounds of compromised bodily integrity and rights of the child. Recently, and for the first time, the UN Human Rights Council adopted a resolution calling on countries to enhance efforts to combat discrimination, violence and harmful practices against people with congenital variations in sex characteristics [27]. Simultaneously, intersex community groups have extensively campaigned against “sex-normalising” interventions on the same grounds, with some suggesting that the existence of such interventions also represent an elimination of intersex communities and an enforcement of strongly normative conceptualizations of gender and sex [28]. The collective impact of advocacy groups and human rights monitoring bodies has been reflected in a growing wave of national and sub-national legislative change restricting the practice of elective genital surgery conducted on children, focusing on the protection of children’s physical integrity and the prohibition of surgical intervention for infants and children with congenital variations in sex characteristics too young to participate in decision-making [29].

Both a 2016 Global Disorders of Sex Development Update since 2006 publication and a 2018 European publication, Caring for Individuals with a Difference of Sex Development, emphasise the need for clinicians to consider the ethical implications of conducting “sex-normalising” surgical interventions, and discuss the postponing of genital surgery until an individual is old enough to understand the intervention and participate in decision-making [2, 4]. Despite this, there is little evidence to suggest that the prevalence of, or rationales for conducting, “sex-normalising” surgical interventions on individuals too young to consent has changed in recent years [30, 31]. Understanding the rationale behind the continued practice of “sex-normalising” surgical interventions and how clinicians acknowledge and contextualise the controversial nature of the interventions they are practicing is necessary for identifying misconceptions in practice, and designing policy and interventions that target common drivers of continued, early surgical procedures.

Our review aims to understand the extent to which the extant medical literature is reporting rationales for elective, “sex-normalising” surgical interventions conducted in infancy and childhood, what these rationales are, and how they are contextualised within the social, medical, and political controversy surrounding “sex-normalising” interventions for people with congenital variations in sex characteristics.

Methods

Results

Search

Our search yielded 11,042 records, with 6,963 undergoing title/abstract screening after de-duplication. Following full-text screening of 1,649 records, 70 met all inclusion criteria and underwent data extraction. One further study was identified from searching systematic, scoping and literature reviews identified from the search (Fig 1). S2 Text details the full search results from each database.

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Fig 1. PRISMA flowchart.

https://doi.org/10.1371/journal.pgph.0003568.g001

Of the 71 studies in the final sample, 73.2% were case studies or case series (n = 52) and 26.8% were cohort studies (n = 19). Countries publishing included studies were India (n = 11; 15.5%), United States of America (n = 7; 9.9%), Brazil (n = 6; 8.5%), Türkiye (n = 5, 7.0%), Japan (n = 4; 5.6%), Algeria (n = 3; 4.2%), United Kingdom of Great Britain and Northern Ireland (UK), Netherlands, Pakistan, Romania, Egypt, Italy (n = 2; 2.8%, respectively), Sweden, Portugal, Republic of Korea, Iran (Islamic Republic of), Canada, Saudi Arabia, Spain, Finland, France, Germany, Indonesia, Argentina, Uganda, Nigeria, China, Poland, North Macedonia, Australia, Iraq, Belgium, Colombia, Kuwait, Syria, Bangladesh, Switzerland and Uzbekistan (n = 1; 1.4%, respectively). Included studies investigated a range of congenital variations in sex characteristics, including 29.6% of studies reporting on congenital adrenal hyperplasia (CAH, n = 21), 15.5% on diphallia and ovotesticular DSD (n = 11, respectively), 8.5% on persistent Mullerian duct syndrome (PMDS, n = 6), 5.6% on mixed gonadal dysgenesis (MGD, n = 4) and 4.2% Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and partial androgen insensitivity syndrome (PAIS, n = 3, respectively). Table 1 reports study characteristics. Quality of studies was generally low, with limited description of patient demographics, surgical interventions, and outcomes (S1 Table).

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Table 1. Characteristics of included studies.

https://doi.org/10.1371/journal.pgph.0003568.t001

Outcomes measured in the literature

Fig 2 is a representation of the outcomes reported in included articles, categorised in line with the recommended reporting outcomes in the 2018 publication Caring for Individuals with a Difference of Sex Development [2]. Fig 2 also indicates which articles reported rationales for the conduct or timing of surgery, and those that acknowledged controversy. The most common outcomes collected in included literature were cosmetic outcomes, primarily reported by surgeons or parents, complication rates and urogenital outcomes. There was a notable lack of validated measures used by studies when assessing any surgical outcome, particularly cosmetic, and no studies collected any data on child quality of life or parental outcomes (i.e., parental mental health).

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Fig 2. Chart reporting the inclusion of rationales and acknowledgment of controversy in included articles, as well as a tabulation of outcomes from and characteristics of included studies, in line with the recommendations from caring for individuals with a difference of sex development [2].

https://doi.org/10.1371/journal.pgph.0003568.g002

Discussion

This manuscript reports the findings of the first systematic review investigating the rationales, outcomes and controversies surrounding elective, “sex-normalising” interventions for infants with congenital variations in sex characteristics. Included articles were largely case reports, matching previous observations about the extant literature [2, 4]. Among a geographically diverse set of articles, we noted outcome reporting that did not align with recommended reporting guidance. Rationales reported by surgical teams both concerning the conduct of interventions and their timings were heterogeneous across included studies, but broadly included anatomical/cosmetic/functional rationales, a perceived desire of aligning with a sex assigned by surgeons and parents, parental desire, and a belief of best practice. Studies acknowledged controversies surrounding the quality of interventions, cultural, gender and social considerations, and the ethics surrounding surgeries, while demonstrating different ways of integrating these controversies into their rationale for the continued justification of surgical intervention. 62.0% of studies reported no specific rationale for intervention timing, 39.4% reported no rationale for conduct and 52.1% acknowledged no controversy in the interventions they were conducting, implying that in some settings these surgical interventions remain accepted, common practice.

Cosmesis emerged as an important rationale for the conduct of interventions, as well as being one of the most commonly reported outcome measures collected in included articles. There was notable subjectivity in the reporting of cosmesis, with subjective, descriptive terminology used by surgeons and parents to determine successful cosmetic outcomes, combined with a lack of validated measures used for outcome appraisal. There is no guarantee that infant genital surgery will improve long-term cosmetic outcomes for the individual concerned; indeed, some adults with congenital variations in sex characteristics who have received surgical intervention in infancy report dissatisfaction and distress associated with their post-surgical genital appearance [90], concerns which will sometimes require multiple repeat surgeries to address [91]. Decisions about genital cosmesis should not be made without the active participation and consent of the individual to whom the genitalia belong, and thus elective, irreversible genital surgical interventions for infants and children with congenital variations in sex characteristics should not take place before the individual can decide for themselves whether they would like to undergo such procedures [92].

19.7% of studies reported parental distress as rationale for either the conduct or timing of interventions, primarily citing an anticipated or voiced parental desire for improved genital cosmesis or for genitals that align more with those associated with ‘typical’ male or female bodies. Medical teams also suggested surgery could relieve psychological distress in parents, improve parental attachment and increase parental comfort. Importantly, a belief that infant surgery was not best practice by surgical teams was occasionally overwhelmed by intense parental desire for intervention in infancy or early childhood, indicating the respect given to parental desire in many settings. Medical teams in some settings struggled with balancing clearly voiced parental desire for early intervention against medical recommendations and human rights imperatives to delay decision-making surrounding intervention until children with congenital variations in sex characteristics are able to participate in decision-making processes. This underscores the need for multidisciplinary teams supporting infants and children with congenital variations in sex characteristics and their parents. Medical teams have a critical role to play in guiding and managing ethical decision-making with parents in clinical settings and sociocultural environments where the rights of the child and obligations of the parents to make decisions which benefit the child do not necessarily match parental desire [93]. Known drivers of parental distress should be better and consistently integrated into parent and family counselling and psychosocial support, and delivered by qualified professionals like psychologists and social workers [4]. This counselling may include, for example, a focus on destigmatising congenital variations in sex characteristics, providing clear supportive pathways for communicating with their child on their variation as they grow, being candid on the risks of early surgery for a child, and connecting parents to the intersex community and parents of children with congenital variations in sex characteristics.

39.4% of studies reported a perceived goal of aligning with an assigned sex from parents or surgeons as a rationale for intervention conduct or timing, with arguments around promoting a specific gender also pervading into cosmetic, functional, and anatomical rationales. These rationales largely rely on the assumption that early life experience, including cosmetic, social, and functional features, predicts future gender identity; a theory cited by several studies when navigating sex assignment controversies [39, 78]. This is reminiscent of mid-20th century arguments about gender identity development, popularized by John Money (the work of whom is cited by some included articles [42, 81] which suggests gender identity is socially constructed in childhood and thus can be re-assigned in infancy, with external factors such as social environment and anatomical features made to match this chosen assignment [94]. Although this theory is now debunked [95, 96], it still pervades in rationales for intervention conduct and a belief that earlier intervention is more efficacious at promoting gender identity development aligned with an assigned sex from parents or medical teams. There is no evidence to suggest surgical intervention for infants with congenital variations in sex characteristics is associated with ‘better’ gender identity development. In fact, several studies note an increased prevalence of gender dysphoria in individuals having undergone “sex-normalising” surgical intervention in infancy [2, 97, 98]. Irreversible, elective genital surgical interventions with the rationale of promoting the development of a specific gender identity are unethical without the full, free, and informed consent and decision-making of the person concerned. Rather, counselling and support for children and parents should be provided throughout infancy, childhood and adolescence, until an individual is old enough to decide for themselves whether they wish to undergo such interventions, and, if they do desire intervention, are able to understand and provide informed consent for any desired interventions.

Forty-six studies were excluded from analysis after full-text screening for citing malignancy as a rationale for conducting interventions, as we determined mitigation of a perceived malignancy risk to be sufficient to consider an intervention to be non-elective. The importance of mitigating the risk of childhood malignancy should not be understated. However, it is important to ensure that the choice to undertake prophylactic genital surgeries (versus a more conservative course of biopsy and monitoring) before a child can provide full, free and informed consent and participate in decision-making processes is done with caution, and that any risk of malignancy is justified and evidence-based. Twenty-six of these forty-six studies cited malignancy as a rationale for surgery for a congenital variation in sex characteristics for which surgical intervention was not recommended as a malignancy mitigation strategy in the 2006 publication, Consensus Statement on Management of Intersex Disorders [9], which was the last guidance to segregate malignancy risk by individual congenital variation in sex characteristics. This echoes a lack of clarity on the malignant potential of different congenital variations in sex characteristics, which is noted in the extant literature [36, 37, 99]. The expertise of this team did not allow for a critical appraisal of the validity of oncological concerns justifying interventions. Future research should focus on fully elucidating causal pathways and epidemiological connections between individual congenital variations in sex characteristics and malignancy to ensure irreversible genital surgeries are not being conducted when biopsy and monitoring may be sufficient malignancy mitigation strategies.

The social and cultural complexity of congenital variations in sex characteristics across different geographic settings and demographic groups was cited as a reason for conducting interventions and permeated throughout discussions about intervention controversy. This was of particular importance when considering parental desire and concerns about raising a child in a setting that could potentially be stigmatising. Attitudes towards people with congenital variations in sex characteristics differ largely across settings, with cultural considerations about gender preference, identity and stigma towards children with congenital variations in sex characteristics driving strong parental and surgeon desire for intervention in certain settings [69, 100]. Concerns about raising a child with congenital variations in sex characteristics should be acknowledged and integrated into discussions with parents (for example, by providing resources, including through peer support from intersex persons and their parents, on how to communicate with other family and community members). Parental or surgeon concerns, however, should not be used to justify the conduct of elective, irreversible genital surgeries before an individual can provide full, free and informed consent.

International human rights treaty bodies have recommended the prohibition of irreversible, elective, genital surgeries conducted on children with congenital variations in sex characteristics before they can participate in decision-making and give full, free and informed consent [25]. Despite this, we identified that interventions continue to be conducted, based largely around heterogeneous anatomical and functional goals that were not adequately supported by recommendations and the extant medical literature, a desire from parents and surgeons to match genital cosmesis with that typically ascribed to male and female bodies, and a parental desire for intervention conduct. In-keeping with the recommendations of human rights bodies, we recommend that human rights, including the rights of the child, should be protected and prioritised by health systems, and, as such, desire for intervention from parents or surgical teams is not sufficient to justify conducting irreversible, elective, genital interventions before a child can decide for themselves if they want or do not want such procedures, and if they do, provide informed consent to any intervention.

There are notable limitations to this review. Our findings are not entirely representative of the diversity of persons with congenital variations in sex characteristics, given the notable discrepancy in the categorisation of these variations across different disciplines and countries. Our conservative approach to study inclusion, such as excluding studies citing generic urological functional goals and all studies citing malignancy regardless of recommendations from oncological literature, may have led to the exclusion of relevant studies. However, a strength of this review is that this conservative approach ensured that all included interventions were clearly elective. There is also likely to be a publication bias towards congenital variations in sex characteristics that aren’t commonly occurring, given the predominance of case reports emerging from our inclusion criteria (i.e., the large number of diphallia cases included, when the variation itself is reported to be limited to one in every five million live births [101]). A decision to exclude articles in which it was not certain if all individuals were under the age of 10, to ensure our findings represented only interventions conducted in infancy and childhood, led to the exclusion of cohort and larger scale studies where these data were not disaggregated by age, potentially biasing the study towards primarily considering lower-quality case reports. Available clinical data lacks adequate sample sizes, independence and relevant control groups [28], undermining the generalisability of the outcomes reported in this review. Although some guidance recommend upscaling longitudinal (including retrospective) outcome assessment studies to address this lack of data [2, 9], it is important that any long-term outcome data is collected from individuals who provided full, free and informed consent to undergo elective, irreversible, genital interventions and to being a participant in any research. Outcome measurements and research priorities should focus on understanding the perspectives, health and wellbeing of the individuals affected and how health services can better meet their current and future needs.

Conclusion

International human rights monitoring and accountability mechanisms call for the deferral of decision-making around elective, irreversible, “sex-normalising” genital surgeries for infants and children with congenital variations in sex characteristics until individuals can participate in decision-making and provide free, full and informed consent to any desired interventions. This review has identified a heterogenous literature reporting the surgical outcomes, rationales, and controversies of surgical interventions, with notably inconsistent study designs, methods, and outcome reporting. Assessment of surgical rationale and outcomes has revealed that medical teams continue to conduct these interventions in the face of controversy due to desires to mitigate parental distress surrounding the perceived difficulties of raising a child with a congenital variation in sex characteristics, as well as a variety of under-researched or outdated beliefs that doing so mitigates suboptimal anatomical, cosmetic, physiological, and psychological outcomes for a child, or that surgical intervention is best practice.

Irreversible, elective, “sex-normalising” genital interventions on infants or children with congenital variations of sex characteristics are unethical without the full, free, and informed consent and active participation in decision-making of the individual concerned. Rationales of achieving a cosmetic outcome perceived as satisfactory by individuals to whom the genitalia do not belong, matching parental desire or alleviating parental distress, or promoting a specific gender identity do not justify continuation of these procedures.

National legislating and medical regulatory bodies, in collaboration with relevant international and regional organisations, should enhance efforts to end the conduct of irreversible, elective, “sex-normalising” interventions conducted without the full, free, and informed consent of the person concerned, in an effort to promote and protect the right to the highest attainable standard of physical and mental health for people with congenital variations in sex characteristics.

Supporting information

Acknowledgments

The authors wish to thank Morgan Carpenter and Mauro Cabral Grinspan for their help to define the review’s search strategy, and Anna Coates, Jenny Cresswell, Eva Krpelanova, Andreas Reis, for their inputs on the review’s results and interpretation.

Disclaimer: The named authors alone are responsible for the views expressed in this publication and do not necessarily represent the decisions or the policies of the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) or the World Health Organization (WHO).