Editing Infertility: Management (section)

===Treatment Selection'''<span style="color:#ff0000">[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]</span>'''===
*'''<span style="color:#ff0000">Testosterone monotherapy should not be prescribed for the male interested in current or future fertility</span>[https://pubmed.ncbi.nlm.nih.gov/33295257/ §]'''
**Exogenous testosterone administration provides negative feedback to the hypothalamus and pituitary gland, which can result in inhibition of gonadotropin secretion.
**Depending on the degree of testosterone-induced suppression, spermatogenesis may decrease or cease altogether, resulting in azoospermia.
**Although recovery of sperm to the ejaculate occurs in most men with cessation of testosterone therapy, the time course of recovery may be prolonged and can be months or rarely years.
***In those that may want to pursue paternity in the more distant future, testosterone therapy may be offered, but the patient should be counseled about the effects on spermatogenesis and the time course required for resumption of spermatogenesis.
*'''Hyperprolactinemia'''
**Etiology of hyperprolactinemia should be treated
*'''Secondary hypogonadism (hypogonadotropic hypogonadism)[https://pubmed.ncbi.nlm.nih.gov/33295257/ §]'''
**Patients with HH present with deficient LH and FSH secretion. In the absence of LH and FSH stimulation, the Leydig cells in the testes do not secrete testosterone, and spermatogenesis is disrupted.
**'''Causes'''
***'''Idiopathic hypogonadotropic hypogonadism (IHH)'''
****'''Congenital'''
*****'''Kallman syndrome'''
******'''Associated with anosmia and the lack of endogenous GNRH secretion'''
****'''Spermatogenesis can be initiated and pregnancies achieved in many of these idiopathic hypogonadotropic hypogonadism men when they are treated with exogenous gonadotropins (hCG, FSH) or GnRH.'''
*****'''Usual first-line drug for the treatment of idiopathic hypogonadotropic hypogonadism for restoration of testosterone and spermatogenesis is hCG'''
******hCG is FDA-approved for use in men with HH
******Degree of response correlates with the size of the testis prior to treatment
******Initial treatment consists of hCG injections (1,500-2,500 IU, twice weekly)
*******Can be followed by FSH, when indicated, after testosterone levels are normalized on hCG
***'''Acquired (adult-onset)'''
****Secondary causes of HH include pituitary or suprasellar tumors, pituitary infiltrative disorders (e.g., hemochromatosis, tuberculosis, sarcoidosis, histiocytosis), exogenous androgens, other medications (e.g., chronic narcotic exposure), hyperprolactinemia, prior head trauma, pituitary apoplexy, and severe chronic illness.
****Management
*****The first line treatment for secondary causes of hypogonadotropic hypogonadism is towards the underlying disorder. Once that has been accomplished, and the patient continues to have hypogonadotropic hypogonadism, a trial of the gonadotropin treatment regimen described above can be initiated.
******SERMs have been used off label as an alternative treatment to increase testosterone and sperm density in men with acquired hypogonadotropic hypogonadism.
*******'''SERM therapy will not be beneficial if the pathology is due to primary pituitary dysfunction, such as after surgical resection.'''
*'''<span style="color:#ff0000">Infertile men with low serum testosterone (and low or normal serum LH)'''
**'''<span style="color:#ff0000">May use aromatase inhibitors (AIs), hCG, selective estrogen receptor modulators (SERMs), or a combination thereof'''
***AIs, hCG, and SERMs act by different mechanisms to increase endogenous testosterone production. Each agent may be used separately or in combination in an effort to increase serum testosterone concentrations without impairing spermatogenesis.
****'''If elevated estradiol levels: consider use of AIs'''
****'''If low or normal serum LH: Either hCG or SERMs may be considered'''
****'''If elevated LH, consistent with primary hypogonadism, may have a limited serum testosterone response to these medications due to inherent testicular dysfunction.'''
***Although the goal of testosterone optimization in the infertile male may be symptom amelioration, symptomatic outcomes and benefits may not be comparable to those achieved using standard (exogenous) testosterone replacement therapy.
*'''<span style="color:#ff0000">Idiopathic infertility'''
**'''<span style="color:#ff0000">Use of SERMs has limited benefits relative to results of ART'''
***Any possible limited benefits of SERM administration, particularly in the patient population with idiopathic infertility, are small and, therefore, outweighed by the distinct advantages offered by other forms of medically-assisted reproduction (e.g., IVF), which include higher pregnancy rates and efficiencies with respect to the earlier timeframe of conception.
**'''May consider treatment using an FSH analogue with the aim of improving sperm concentration, pregnancy rate, and live birth rate'''
***
*'''Non-obstructive Azoospermia'''
**For any patient with NOA, it would be ideal to optimize spermatogenesis and hence the chances of sperm recovery at the time of attempted surgical sperm retrieval.[https://pubmed.ncbi.nlm.nih.gov/33295257/ §]
**'''Limited data supporting pharmacologic manipulation with SERMs, AIs, and gonadotropins prior to surgical intervention.'''