Reproductive

1.5-60%

Moderate

for disorders of sex development and idiopathic male infertility with targeted NGS and exome sequencing

System Profile

Yield Comparison

Red Flag Combinations

Clinical patterns that should prompt consideration of genetic testing

● Delayed puberty + anosmia

● Ambiguous genitalia + salt-wasting

● POI + streak ovaries

● Infertility + bronchiectasis

Screening Decision Pathway

When to consider genetic testing for reproductive presentations

        graph TD
          START["Patient Presents with\nReproductive Concerns"] --> SCREEN{"Screen for\nRed Flags"}
          
          SCREEN --> RF1["Abnormal puberty or menstrual cycle screening ques..."]
          
          SCREEN --> RF2["Tanner stage discrepancies"]
          
          SCREEN --> RF3["Newborn DSD screening flags"]
          
          
          RF1 --> EVAL{"Multiple\nFlags Present?"}
          
          RF2 --> EVAL{"Multiple\nFlags Present?"}
          
          RF3 --> EVAL{"Multiple\nFlags Present?"}
          
          EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
          EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
          TEST --> DX["Molecular Diagnosis\n1.5-60% yield"]
          style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
          style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
          style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e

Screening Red Flags

Findings on routine screening that may indicate genetic etiology

Abnormal puberty or menstrual cycle screening questionnaires
Tanner stage discrepancies
Newborn DSD screening flags

Exome / Genome Sequencing Indications

Clinical scenarios supporting ES/GS as a diagnostic approach

Ambiguous genitalia
Unexplained infertility
POI
Complex pubertal disorders
DSD with nondiagnostic first-tier endocrine/genetic tests

Key Evidence

Published studies supporting genetic testing for reproductive conditions

Study	Year	Type	Sample	Yield	Key Finding
Exome sequencing for the diagnosis of 46,XY disorders of sex...	2015	Cohort	40	35%	Exome sequencing achieved 35% likely genetic diagnosis in 46,XY DSD patients (22...
WES-discovered FSHR mutation causing primary ovarian failure	2016	Cohort	None	None	WES identified homozygous FSHR variant as cause of primary ovarian failure in co...
Novel SRY Mutation R75M Causing 46,XY Complete Gonadal Dysge...	2016	Case Report	1	None	De novo SRY R75M mutation identified by trio WES causing 46,XY complete gonadal ...
New NR5A1 mutations and phenotypic variations of gonadal dys...	2017	Cohort	4	None	Exome sequencing identified 3 novel NR5A1 mutations in 4 DSD patients with broad...
Validation and Application of a Novel Integrated Genetic Scr...	2017	Cohort	None	1-1.5%	1-1.5% monogenic diagnostic rate in 1,112 infertile men; idiopathic male inferti...
PPP2R3C Variants Cause Syndromic 46,XY Gonadal Dysgenesis	2019	Case Report	4	None	PPP2R3C biallelic variants cause novel syndromic 46,XY gonadal dysgenesis in 4 g...
Translating genomics to the clinical diagnosis of disorders/...	2019	Review	None	None	Comprehensive review of genomic tools for DSD diagnosis including CMA, ES, GS an...
A missense mutation in NR5A1 causing 46,XX female to male se...	2020	Case Report	1	None	WES identified a novel NR5A1 missense variant causing 46,XX sex reversal in an I...

Updated: 2026-02-25 Curated by: human Status: human reviewed

Reproductive

System Profile

Yield Comparison

Clinical Dimensions

Red Flag Combinations

Screening Decision Pathway

Screening Red Flags

Exome / Genome Sequencing Indications

Key Evidence

Linked Literature

Key References

Related Cases

Efficacy Measures