**Core Concept**
Ambiguous genitalia refer to a condition where the external genitalia do not clearly appear male or female, typically presenting at birth. This condition arises due to an abnormality in the development of the genital ducts, gonads, or sex chromosomes during embryogenesis. The underlying pathophysiology involves the interplay of genetic, hormonal, and anatomical factors influencing sex determination and differentiation.

**Why the Correct Answer is Right**
The correct answer is related to the fact that ambiguous genitalia are not seen in individuals with a typical 46,XY karyotype. In such cases, the presence of a Y chromosome leads to the production of androgens, which typically causes the development of male external genitalia. However, in certain conditions like congenital adrenal hyperplasia (CAH), the accumulation of androgens due to a deficiency of 21-hydroxylase can cause virilization of female external genitalia, leading to ambiguous genitalia.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it is possible for individuals with a 46,XY karyotype to present with ambiguous genitalia due to conditions like CAH or complete androgen insensitivity syndrome (CAIS).

**Option B:** This option is incorrect because individuals with a 46,XX karyotype can present with ambiguous genitalia due to conditions like congenital adrenal hyperplasia (CAH), which leads to the accumulation of androgens causing virilization of female external genitalia.

**Option C:** This option is incorrect because it is possible for individuals with a 45,X karyotype (Turner syndrome) to present with ambiguous genitalia, although this is less common.

**Clinical Pearl / High-Yield Fact**
A key point to remember is that ambiguous genitalia can result from a variety of genetic, hormonal, and anatomical abnormalities, and a thorough evaluation, including karyotyping and hormonal assays, is essential for determining the underlying cause.

**Correct Answer: D.**