Review article
Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

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Summary

Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and “non-hormonal/non chromosomal” DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts.

Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should lead to design collaborative prospective studies involving all parties and using consensual protocols of evaluation.

Introduction

Ten years after the Chicago consensus meeting [1], genital surgery continues to raise questions and criticisms concerning its indications, its timing, and its technical aspects [2], [3]. Opinions are more common than facts as the volume of patients in each group of disorders of sex development (DSD) is small, management is extraordinarily heterogeneous across centers, and pre- and post-treatment evaluations are mostly subjective, examiner-dependent, and culturally influenced. Hence, the classical methodology of evidence-based medicine meets major hurdles, which are responsible for several unanswered questions that we attempt to list in this standpoint article.

The first major hurdle is the definition of the acronym DSD. Does it include all congenital developmental genito-sexual anomalies, and, if so, are undescended testicles, hypospadias, or even labial adhesions included? Or should the definition be limited to situations in which there is an inadequacy between genital anatomy (phenotype) and biological profile (biotype), which may raise questions about gender assignment? This restrictive definition of DSD does not identify genital anomalies with no detectable biological or chromosomal anomalies, which represent the vast majority of patients.

The second hurdle is semantic as the terms “gender,” “sex,” “sexual,” have discordant interpretations. “Gender” is a social concept, which is the way the society mirrors the “individual identity.” It does not take into account the “individual identity” (“inside identity”) and the future “gender role” (“behavioral identity”), which are invisible at birth and the modalities of which are mostly unknown, that is multifactorial [4]. The term “genital” has been avoided in the Chicago meeting, although atypical genito-sexual development should be the main focus of this discussion. Hence, it is essential to correlate phenotype and biotype as atypical anatomy is the first clinical sign from which suspicion of a DSD is raised in the newborn and will lead to a chain of investigations to define to which group of DSD the patient belongs.

Section snippets

Who are we talking about? What difficulties are met in the management of each of the following DSD groups?

Using the Chicago canvas [5], five main groups of DSD patients may be identified, submitted to the gender assignment process, and may be considered for a surgical genital reconstruction.

  • (1)

    In the 46,XX DSD group, classical congenital adrenal hyperplasia (CAH) represents the most common diagnosis. There is usually no gender issue in this group, except in case of late diagnosis and severely masculinized 46,XX individuals. Genital phenotype of prenatally non-treated 46,XX CAH patients at birth

Aims of surgery

  • Restore functional genital anatomy to allow future penetrative intercourse (as a male or a female),

  • Facilitate future reproduction (as a male or a female) when possible,

  • Reduce urological hazards related to abnormal genito-urinary anatomy, that is urinary tract infections, with potential upper urinary tract consequences and urinary incontinence,

  • Avoid fluid or blood retention in vaginal or uterine cavities,

  • Avoid late virilization at puberty in individuals raised as girls or breast development in

The context of decision

Before birth: When there is an index case in the family, especially CAH, targeting fetuses at risk has been considerably improved with early detection of fetal DNA (SRY) in maternal serum at 4–5 weeks of gestation, followed by chorionic villus sampling at 10 WG to possibly treat with dexamethasone affected 46,XX CAH fetuses. This option aims at diminishing fetal virilization [25], [40].

In other cases, discrepancies between prenatal ultrasound findings and fetal karyotype may raise the question

Where do we stand in 2015 with these very distinct situations?

To attempt to answer this question, a detailed questionnaire reviewing the most difficult clinical situations was sent to several world DSD experts.

Conclusions

It appears obvious that given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure, and the evaluation of outcome of DSD surgery. The levels of evidence of the answers given by the experts are low (B and C), most decisions being supported by team expertise. Literature mostly reports short clinical series, which cannot be compared considering the heterogeneousness of pathologies and management between centers. There are,

Conflict of interest

None.

Funding

None.

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