Perspectives on conducting “sex-normalising” intersex surgeries conducted in infancy: A systematic review

Children with intersex variations continue to be subject to elective, irreversible, “sex-normalising” surgical interventions, despite multiple human rights and legislative bodies calling for their prohibition. Our systematic review aims to understand how medical literature reports rationales for “sex-normalising” surgical interventions conducted in childhood, and how they are contextualised within the medical and social controversy surrounding such interventions. PubMed, EMBASE and CINAHL were searched for English language, peer-reviewed articles reporting primary data on elective, genital, “sex-normalising” surgical interventions conducted on individuals <10 years, published 01/07/2006-30/06/2023 (PROSPERO ID: CRD42023460871). Data on outcomes reported, rationale for the conduct and timing of interventions and acknowledgement of controversy were extracted. Narrative synthesis described rationales and controversy. Risk of bias was assessed using Johanna Briggs Institute Tools. 11,042 records were retrieved, with 71 articles included for analysis. One of the most common outcomes collected in included literature were cosmetic outcomes, primarily reported by surgeons or parents. 62.0% of studies reported no rationale for intervention timing, 39.4% reported no rationale for conduct and 52.1% acknowledged no controversy in intervention conduct. Rationales included parental desire for intervention, anatomical/functional/cosmetic reasons, and a perceived goal of aligning with sex assigned by surgical teams or parents. Controversies addressed included concerns about the quality of interventions, the ethics of intervention conduct and gendered and social considerations. “Sex-normalising” interventions are conducted based largely on rationales that were not adequately supported by evidence, a desire from parents and surgeons to match genital cosmesis typically ascribed to male and female bodies, and a parental desire for intervention conduct. Legislating and medical regulatory bodies should advocate for ending the conduct of irreversible, elective, “sex-normalising” interventions conducted without the full, free and informed consent of the person concerned, to promote and protect the highest attainable standard of health for people with intersex variations.


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][6][7][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][11][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][14][15][16][17][18][19][20][21][22][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.

Search and screening
Our review was compliant with PRISMA Reporting Guidelines [32] (see S1 text), and is registered with PROSPERO (CRD42023460871).
On 30/06/2023, PubMed, EMBASE and CINAHL were searched for relevant articles published between 01/07/2006-30/06/2023, using search terms derived from previous reviews, recommendations from field experts and terminology from the International Classification of Diseases, .The search start date aligns with the year of publication of the 2006 Consensus Statement on Management of Intersex Disorders [9].
S2 Text reports our search strategy.One search filter captured medical and public health terms that covered intersex as an umbrella term as well as individual congenital variations in sex characteristics that are generally identified in infancy or early childhood (as opposed to during puberty or adulthood).A second search filter captured general surgical terms as well as specific procedures associated with genital surgery for persons with congenital variations in sex characteristics [4].English language restrictions were applied due to the risks of losing the complex nuances of surgical rationale in translation.A final search filter attempted to exclude: animal studies; commentaries, letters, and editorials; studies covering gender-affirming care surgeries; studies focusing on adolescence or young people over the age of 10 years.
Title/abstract and full-text screening was carried out by LM and CLA.
LG independently screened a random sample of 10% of full texts to ensure consensus between reviewers.Screening was conducted in the systematic review management software, Covidence [33].

Inclusion and exclusion criteria
Peer-reviewed journal articles reporting primary data on elective, genital, "sex-normalising" surgical interventions conducted before the age of 10 years were included.This age cut-off was selected to align with the WHO's definition of adolescence (ages 10-19 years) [34].Inclusion decisions regarding surgical interventions were guided by the Gardner and Sandberg terminology of 'urgent' vs 'elective' surgery, with 'urgent surgeries' referring to those "performed promptly to avoid life-threatening circumstances or to prevent permanent disability", while 'elective surgeries' include "those that address non-urgent issues" [35].
The following exclusion criteria were developed: • Malignancy.Articles that cited malignancy as their rationale for conducting surgeries were excluded.Some individual congenital variations in sex characteristics are associated with increased risk of germ cell tumours, which is sometimes cited as a rationale for surgical intervention, despite the general malignancy risk associated with congenital variations in sex characteristics being debated [36,37].However, for this review, it was thought that the potential for malignancy as perceived by clinicians and presented to parents/guardians, would, in the eyes of concerned parties, change the suggested surgery from being considered 'elective' to 'urgent'.Whether surgical intervention due to the potential risk of malignancy was recommended for the specific congenital variation in sex characteristics in the 2006 Consensus Statement on Management of Intersex Disorders [9], which was the last statement to tabulate malignancy risk by individual variation, was recorded, and addressed in the discussion.
• Urinary incontinence.Studies citing preserving urinary continence, or studies citing functional urological goals (e.g., removing urethral obstruction), as their rationale were excluded, as these interventions were deemed to be non-elective [35].Studies whose stated urological goals were intended to bring an individual in line with a perceived normative social behaviour (e.g., surgery to allow a boy to urinate standing up rather than sitting down) were included.
• Age.Studies in which it was unclear if all participants were under 10-years-old (i.e., age range was not provided), or studies which reported outcomes for a combination of individuals aged above and below 10-years-old without segregating outcomes, were excluded.
• No patient outcome data.Studies that collected no patient outcomes (e.g., studies focusing on surgical equipment use, histological studies) were excluded.
• Hypospadias, epispadias or cryptorchidism.Studies addressing hypospadias, epispadias or cryptorchidism that did not present these variations as congenital variations in sex characteristics or did not investigate them as part of an established congenital variation in sex characteristics were excluded due to debate among the medical community over their status as congenital variations in sex characteristics.
• Primary focus not "sex-normalising" surgical interventions.Studies that reported patients who had previously received a "sex-normalising" intervention but did not report the outcomes of or rationale for that surgery were excluded.
• Non-intersex populations.Studies that reported interventions that could be classed as "sexnormalising" but were administered to patients both with and without (e.g., transgender and gender diverse patients) congenital variations in sex characteristics without segregating outcomes for individuals with congenital variations in sex characteristics, were excluded.
• Reviews.Relevant systematic and scoping reviews were excluded but studies included in the reviews were screened against our inclusion criteria as part of a secondary search strategy.

Data extraction
Data extraction was conducted in Covidence [33], using a data-extraction table constructed by LM.LM and LG independently extracted, with CLA extracting a random sample of 25% of studies.In addition to bibliometric data (e.g., author, year of publication), the following data were extracted: • Surgical outcomes.In line with the recommendations for data collection on long-term surgical outcomes for individuals with congenital variations in sex characteristics in the 2018 publication Caring for Individuals with a Difference of Sex Development [2], we recorded if studies reported: complication rates, success rates, cosmetic outcomes, quality of life, sexual functioning, urogenital outcomes, sexuality/gender assignment, re-evaluation, fertility outcomes, social and psychosexual adjustment, mental health, social participation and parental outcomes.The precise and detailed categorisation of long-term outcome reporting used in the 2018 publication was deemed most appropriate for tabulating outcomes, rather than the 2006 Consensus Statement on Management of Intersex Disorders [9] or the 2016 Global Disorders of Sex Development Update since 2006 [4].
• Rationale.We recorded whether studies provided a rationale for conducting the surgical intervention, as well as rationale for the timing of the surgery.Rationales were extracted verbatim, alongside any work cited by authors when justifying rationale.
• Acknowledgement of controversy.We extracted verbatim text from studies that acknowledged the social, political, cultural, medical, ethical and/or surgical controversy surrounding the intervention they were conducting, as well as any work cited by authors when discussing this controversy.
Quality assessment was conducted independently by LM and CLA using the Joanna Briggs Institute's instruments for Quality Assessment [38], with consensus reached through discussion.As no syntheses of outcomes were conducted, and rationale and controversy reporting were deemed to be independent of manuscript quality, manuscripts were not excluded on the basis of low quality.

Data analysis
Descriptive statistics were used to present the number of studies reporting each of the aforementioned outcomes.Qualitative, verbatim data on rationale and controversy was analysed using a narrative synthesis with an inductive approach.LM, LG and AN independently reviewed data to identify codes which addressed commonly occurring themes.LM, LG, and AN met to discuss and agree upon these high-level themes, after which LM independently coded all articles, discussing and refining emerging subthemes with LG and AN.
Throughout the narrative synthesis, the names of congenital variations in sex characteristics used by study authors will be used to avoid unintentional change in diagnosis through misinterpretation by the authorship team.These terms may not always be the accepted term within the intersex or medical communities.
Justifications and rationales for surgical intervention are presented in the narrative synthesis as presented by study teams, regardless of the accuracy of the assumptions stated.The presentation of such rationales does not represent an endorsement of their validity, and the accuracy of stated rationales is explored in the discussion.

Search
Our search yielded 11,042 records, with 6,963 undergoing title/abstract screening after deduplication.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.
Anatomically, surgical interventions were proposed as a way to prevent perceived incorrect virilisation of children and to align genitalia with the perceived 'typical' anatomy of the sex proposed by parents or surgeons [5,7,43,58,59].Studies often articulated this by proposing interventions as a way of resituating anatomical structures to their 'typical' position [54,60].As with cosmetic outcomes, goals were unspecific [61], with some teams describing the results they were striving for as 'satisfactory' [8,49,50,62].Preventing downstream complications associated with ambiguous genitalia, such as endometriosis in Herlyn-Werner-Wunderlich Syndrome [63], was also cited as anatomical rationale for intervention conduct.Anatomical justifications were also used to select and justify the type of procedure being offered, such as one surgical team electing for 'conservative' approaches to minimise tissue removal for children who do not yet have definitive gender identity [64].There was a notable impression by some authors that anatomical goals were secondary to aforementioned cosmetic rationales [50].
Many functional rationales were unspecific and subjective, including achieving 'satisfactory' [57], 'good' [8,52], 'proper' [40], 'typical' [56], 'favourable' [55] or 'desirable' [53] functional outcomes.More specific functional goals included achieving sexual function, including the prospect of 'successful' future intercourse (with the implication that sexual intercourse constituted penis-in-vagina, penetrative sex) [42,45,48] and achieving sexual arousal [5,41,44,50], menstruation [5,42,43] and protection of fertility [5,62].Follow-up times for studies were often not long enough to be able to reliably confirm these functional goals (Table 1).One study suggested a recent shift in prioritisation by global surgical teams towards protecting sexual satisfaction and sensate genital tissues in interventions [44].There were also notable instances in which authors recognised uncertainty surrounding the functional impact of interventions, with articles suggesting post-intervention genitalia may be 'more natural looking, and possibly functioning [emphasis added]' [47] and that interventions 'may facilitate sexual intercourse [emphasis added]' [45].Similar to anatomic rationales, some authors implied functional outcomes were secondary to the cosmetic results they desired [46,50].Rationale for timing of procedure.Cosmetic rationalisations for early intervention were often identical to those justifying the conduct of procedures, with no clear distinction articulated on the relative benefits of conducting these interventions in infancy.Some studies argued that the long-term psychological impact of the appearance of ambiguous genitalia is greater if interventions are not conducted early, without citing any recommendations or wider literature justifying this [6,39].Other studies suggested that better compliance from patients and a lack of recollection in adulthood should justify early conduct of interventions [55].Anatomical justifications for early surgery were more detailed, centring around the argument that early conduct is associated with better surgical outcomes.Several studies suggested that increased oestrogen exposure in the first month of life will provide better vascularised tissue and thicker walls of vaginal tissue [7,55], with other studies providing alternate developmental anatomical justifications, such as undeveloped penile circumflex arteries in infants leading to reduced risks of intra-operational bleeding (an uncited justification) [44].Early age was also suggested to be the most appropriate time for preventing a range of complications that could have lifelong effects [61,63,65,66].Studies also suggested general higher success rates of operations conducted in infancy, without expanding on the specificities of this [67]."Sex-normalising" interventions in infancy were also rationalised in infants requiring multiple surgeries.For example, one study suggested the benefits of concurrently performing vaginal reconstruction in a child with MRKH syndrome who incidentally had an anorectal malformation, with the justification that scarring of the urinary tract and rectum from anorectal reconstruction in this case may make vaginoplasty more difficult in later life [68].Early intervention was also suggested as a way to prevent anticipated incorrect virilisation and puberty associated with retained gonads, the justifications for which were uncited [62,69].Interestingly, one included study initially promoting early surgical intervention changed their mind following their study, moving to advocating for delaying intervention until puberty, with the anatomical justification that post-pubertal genital skin is more robust than the introital skin of infants [7].Functional justifications for early intervention centred around the fact that early surgery will more effectively achieve desired function outcomes [61], including maintaining reproductive potential [63] and metabolic development [62].
Perceived goal of aligning with assigned sex.The 28 studies reporting a perceived goal of aligning with an assigned sex as a rationale for the timing or conduct of procedures investigated CAH (n = 14), ovotesticular DSD (n = 4), 5-alpha reductase deficiency, MGD (n = 2, respectively), MRKH syndrome, true hermaphroditism, unspecified DSDs, ambiguous genitalia and 46, XX DSD (n = 1, respectively).
Rationale for conducting procedure.Rationalising procedures through pursuing a binary assigned sex for infants manifested in several ways.Anatomically, articles cited an intention to use interventions to create 'normal' external genitalia corresponding with the assigned sex of the infant by parents or surgeons [7, 8, 40, 42-44, 70, 71] or to remove genitals unconcordant with the sex assigned to infants [7,65,[70][71][72][73].Some articles went further than this and identified interventions as a way to manifest the assigned sex (and subsequently, gender identity) chosen for the infant [5,74], suggesting interventions could 'create anatomical [. ..] female gender [emphasis added]' [58] or 'convert to the male sex [emphasis added]' [75].Facilitating psychosocial adjustment through conforming to a binary sex was also cited as an ethical motivation for conducting interventions [43,45,76], based on the assumption that genital appearance influences the development of the sexual psyche [39].Teams also suggested that intervention could achieve certain sexual orientations and sexual development associated with the assigned sex [62], with one study citing hysterectomy and vaginectomy in CAH patients as a way to provide 'satisfactory male gender identity and heterosexual orientation' [62], and another suggesting intervention would facilitate the infant becoming a 'functional member of the society' [77].
Rationale for timing of procedure.The key rationalisation of early intervention timing when enacting the perceived goal of aligning with an assigned sex was the assumption that earlier intervention will more effectively facilitate gender identity development in line with sex assigned to a child by parents or surgeons, and limit psychological distress associated with an ambiguous sex [5,6,41,42,46,62,70,74].One study extends this to suggest that early intervention will facilitate healthy body image development, a suggestion that did not cite any recommendations or relevant literature [39].Some rationales relied on a belief that gender identity formation occurs in early life and can be strongly influenced by environmental surroundings [39,78].Others cited early intervention as key for preventing psychological distress, without detailing the specific reason or evidence-base as to why early intervention is protective against this [8,44].One study cites early intervention as an important tool to prevent societal barriers related to assigned sex for people with congenital variations in sex characteristics, specifically highlighting the complicated sports life in female athletes with 5-alpha reductase deficiency [79].
Rationale for conducting procedure.Several articles predicted that external genital appearance that did not match conventional conceptions of male or female bodies would increase parental anxiety, distress and embarrassment, and used mitigating this as a justification for intervention [7].One study specifically identifies the anticipated parental embarrassment surrounding a large clitoris in a child with CAH as a rationale for intervention [39].Articles also assumed that parental acceptance and parent-child attachment would be improved through surgical intervention, despite often citing no relevant literature or discussions with family to justify this [6].Surgical teams also articulated a difficulty in navigating voiced parental distress.Two surgical teams report going against their own recommendation to delay treatment due to intense parental desire for early intervention [40,78].Parental desire was not only expressed for surgical intervention, but also for the assigned sex of their child.One study reported a strong parental preference to raise their child with ovotesticular DSD as a girl, which was then used as a rationale for conducting reconstructive vaginoplasty [80].
Rationale for timing of procedure.Some articles anticipated that specifically early reconstruction would alleviate anticipated psychological distress in parents [7,8,41], improve parental attachment [69,70] and increase parental comfort [62].One study cites parents asking for early orchiopexy for their child with ovotesticular DSD before they began school to ensure wellbeing within the family, school and wider society [71].In some cases, authors acknowledged that conducting early intervention was going against current global trends towards delaying intervention, but used strong parental desire in their local context to justify this.For example, one study cited parental anxiety specifically resulting from their sociocultural context as reason to complete the procedure as soon as possible [69].Ethical justifications relating to preventing parental harm were also used to justify early intervention, with one study stating the birth of a child with ambiguous genitalia is a 'tragedy' for parents and thus 'prolonging this suffering' is morally unjustifiable [81].
Belief of best practice.The 7 studies reporting belief of best practice as a rationale investigated CAH (n = 5), unspecified DSDs and ambiguous genitalia (n = 1, respectively).
Rationale for conducting procedure.All included studies citing clinical documentation to justify interventions cite the 2006 publication, Consensus Statement on Management of Intersex Disorders [9], referencing its recommendations to conduct surgical interventions in cases of severe virilisation, with the goal of not only improving cosmesis but also future sexual function [6,41,54,67].
Rationale for timing of procedure.Studies similarly cited the 2006 publication, Consensus Statement on Management of Intersex Disorders [9] when justifying early intervention in cases of severe virilisation [6,41], as well as citing clinical practice guidelines from the Endocrine Society [40,43,67,82] and recommendations from a range of government health authorities [45,83].
Access.One study from the UK investigating CAH reported a logistic issue justifying the timing of infant genital surgery [78].Despite teams advocating delayed intervention to parents, an imminent move by the family to their country of origin led the clinical team to elect to conduct the intervention in their specialist unit rather than risk the intervention being conducted in non-specialist facilities at a later date.

Acknowledgement of controversy
Culture/gender/social well-being.Studies that addressed controversies surrounding the cultural, gender and social considerations of interventions introduced this debate through discussing the age of gender identity and sexual development, largely suggesting that by 2-3 years of age, children may be able to correctly label themselves of a certain gender, thus justifying intervention before this age [39,78].Some studies recognised that controversies surrounding sex determination were increasing [7], particularly with concerns around higher prevalence of gender dysphoria among individuals with congenital variations in sex characteristics due to assignment of sex not matching future gender identity [42,64,69].Often these controversies were dismissed through authors citing previous experience or small-scale qualitative evidence citing low levels of gender-related regret in adults having undergone infant genital surgery [64,78].The rights of the child and perceived rights of parents also pervaded in these debates, with authors debating the gender preferences of families and the future gender identity of individuals with congenital variations in sex characteristics [46,71,73,75].In addition to the aforementioned ways of navigating these controversies, such as offering patient-centred, multidisciplinary, individualised care for patients [7,46,64,71], studies also cited the possibility of a sex reversal later in life to rationalise controversial decisions to undergo procedures [71,74,79] or recommended psychological support for children who develop gender dysphoria from incorrect sex assignment from surgeons or parents post-intervention [69,75].Authors also justified intervention in the face of these controversies by suggesting conservative surgery could balance future risks of gender dysphoria while protecting children from growing up in non-accepting environments [64,71].
Ethics.A range of ethical controversies were acknowledged by included studies, primarily concerning the ability to provide informed consent for an irreversible intervention in infancy, and the interventions' implied impact on cosmesis and gender identity [40,42,53,64,69,78].Some studies further extend this debate to discuss the relative rights of the individual and the perceived rights of parents/guardians to request such intervention [46,55,74,81].There is a recognition in some articles about a changing trend in the ethical approach to "sex-normalising" interventions, suggesting a global trend towards prioritising rights of the individual and postponing interventions [46,71].These ethical controversies were navigated in different ways.Often ethical concerns were considered but not explored or integrated into decisionmaking [86,88].The aforementioned surgical, functional, and anatomical rationales are also used by authors as considerations that overwhelm the ethical concerns of interventions, despite many concurrently noting that evidence on the relative efficacies of early and late surgery are lacking [40,53,55,74].Notably, one team changed their recommendations to promote later intervention after their study, citing ethical concerns arising when considering high complication rates and low patient satisfaction with early intervention [42].Placement of the global ethical debate within the context teams were working was also used to rationalise why teams found it appropriate to continue to conduct interventions, primarily suggesting that perceived rights of parents overwhelm the rights of the child in certain settings [46,69,74,75].Other studies introduced ethical controversies surrounding interventions but rationalised their conduct through providing individualised care to patients from a multidisciplinary team and providing psychological counselling to those involved [69,71].Some studies adapted their interventions based off of ethical concerns about irreversibility [64], with authors of one diphallia study promoting early surgery using a technique that did not remove penile tissue as a way to (in their view) address ethical concerns surrounding irreversibility [86].One study adapted their study to focus on vaginoplasty rather than clitoroplasty in their report on a child with CAH to incorporate ethical concerns, due to vaginoplasty being 'less debated' in their setting [89].

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.

Fig 2
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).

Fig 2 .
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

47 .
9% of studies (n = 34) acknowledged controversy surrounding the interventions they were reporting.Three codes were developed to describe studies' acknowledgment of the controversy surrounding "sex-normalising" surgical interventions: controversy surrounding the quality and standards of care (n = 29), controversy surrounding the cultural, gender and social wellbeing implications of interventions (n = 18) and controversy surrounding the ethics of the procedure (n = 15).

Table 1 .
(Continued) Terminology used for congenital variations in sex characteristics matches those reported by authors and does not necessarily reflect the current or correct terminology used in medical practice or by the intersex community.2.Terminology used for surgical interventions matches those reported by authors and does not necessarily reflect the current or correct terminology used in medical practice or by the intersex community.3.Relevant sample size is the number of patients within a cohort or case series that meet all inclusion criteria.https://doi.org/10.1371/journal.pgph.0003568.t001