Diagnosis of Male Infertility: Diagnostic Work-up of the Infertile Man

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Abstract

The diagnostic workflow to evaluate male infertility follows a systematic approach to elucidate previous factors influencing fertility and the present status. The medical history should be taken, preferably in the presence of the female partner, and a clinical examination focusing on testicular morphology and function is done, followed by laboratory tests of gonadotropins and androgens as well as semen analysis according to the World Health Organization criteria. Depending on the results, more elaborate investigations may be necessary, such as the genetic background of male infertility or analysis of testicular spermatogenesis. To better characterize the functional capability of spermatozoa, modern analytical instruments such as DNA fragmentation and methylation analysis or Raman spectroscopy of spermatozoa are used for scientific evaluation. Finally, the differential diagnosis of hypothalamic–pituitary or testicular malfunction will determine the treatment options. Endocrine, surgical, or empirical treatment options such as assisted reproductive techniques can be applied after interdisciplinary diagnosis of both partners, male and female, by the andrologist and a specialized gynecologist to obtain optimal treatment options for the couple.

Introduction

The diagnostic work-up of the infertile man aims at identifying disorders of male infertility for a better understanding of the reasons for a couple's childlessness, to offer adequate counseling, and to offer the best treatment options either to improve fertility for spontaneous conception or to apply assisted reproductive techniques (ART). A diagnostic work-up should be started after 1 yr of regular sexual intercourse without spontaneous induction of pregnancy. Overall, 10–15% of couples are affected, and in about half of those, male factors contribute to childlessness (Table 1).

Disorders of male infertility can arise from dysfunction of the hypothalamic–pituitary region, from the testes themselves, or from post-testicular problems. In general, male infertility is a poor prognostic indicator of a couple's chances of achieving natural conception.

The approach to the diagnostic work-up should be systematic and structured (Table 2) and should start with noninvasive investigations.

Section snippets

Medical history

The purpose of taking the medical history is to get information about a variety of factors such as the duration of infertility, the age and gynecological cofactors of the female partner, previous or present medication used that may affect the hypothalamic–pituitary–gonadal axis, a history of cryptorchidism, sexual and ejaculatory disorders including frequency of sexual intercourse, exposure to toxic agents such as smoking and alcohol, previous pelvic or genital surgery, pubertal development or

Ultrasound

The clinical examination is directed primarily at signs of scrotal pathologies (eg, varicoceles, tumors, spermatoceles, or aplasia of the vas deferens) or penile pathologies (eg, hypospadia, phimosis) but also at signs of male hypogonadism, prepubertal status, undervirilization, or gynecomastia as a sign of hormonal imbalance and body mass index.

Scrotal ultrasonography is mandatory for male infertility patients because the risk for testicular tumors is increased to 1 in 200–300 men, and most of

Hormones

Hormone analysis is the backbone of the andrologic work-up of infertile men because the gonadotropins reflect either primary testicular or pituitary failure. Basically, the measurement of luteinizing hormone (LH), FSH, and testosterone may be considered sufficient and cost effective and should be measured in all men seeking an infertility work-up [21]. However, in case of any abnormal finding, the endocrine evaluation has to become more elaborate.

To evaluate Leydig cell function, total

Semen analysis

The key element of the diagnostic work-up is semen analysis according to the World Health Organization (WHO) guidelines, with revised reference values (Table 3). These reference values are based on the results of a worldwide prospective multicenter study of 1941 men who fathered children within an observation period ≤12 months [25]. The lower reference limits given correspond to the lower 5th percentile (Table 3).

Standardized semen analysis comprises volume and pH, sperm concentration and total

Genetic work-up of infertile patients

The frequency of genetic disorders is increased in patients with severe male factor infertility and varies between oligozoospermic and azoospermic patients from 4.3% to 20.6%, respectively. In particular, chromosomal anomalies are 10–15 times more common than in the normal male population [34]. Additional investigations includes genetic chromosomal analysis, screening for specific defects of the Y chromosome such as azoospermia factor (AZF) deletions, and testing for cystic fibrosis

Testicular biopsy and histologic analysis

Diagnostic testicular biopsies are not indicated for a infertility work-up. If testicular biopsies are taken in azoospermic or cryptozoospermic men, this should always be combined with therapeutic (microsurgical) sperm extraction techniques with the option to cryopreserve spermatozoa for later use with ART. In oligozoospermic men, testicular biopsies may be indicated if TIN is suspected in case of microlithiasis or in the presence of a history of a contralateral testicular tumor. Prior to

Conflicts of interest

The author has nothing to disclose.

Funding support

None.

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