What are the treatment options for genetic and convalescent cases associated with infertility?

Treatment Options for Genetic and Convalescent Cases Associated with Infertility

For patients with genetic or post-illness infertility, treatment should be guided by the specific underlying cause, with options ranging from medical therapy to assisted reproductive technologies depending on the diagnosis. 1

Genetic Causes of Infertility

Chromosomal Abnormalities and Genetic Testing

• Genetic testing should be offered to all males with congenital bilateral absence of vas deferens (CBAVD) or cystic fibrosis (CF), as these conditions have strong genetic associations 1
• CFTR mutation analysis is particularly important for men with CBAVD, with significant associations between F508del mutation and CBAVD (OR = 22.20) 1
• When CF or CBAVD is identified, the female partner should also be screened for CF gene abnormalities to assess risks to potential offspring 1
• In cases of CBAVD where no CFTR mutations are identified, renal ultrasonography is indicated to rule out associated renal anomalies 1

Treatment for Genetic Causes

• For men with genetic causes of azoospermia, microdissection testicular sperm extraction (micro-TESE) is a strong treatment option with sperm retrieval rates of 40-60% 1
• Surgical sperm extraction techniques (TESE, TESA) followed by intracytoplasmic sperm injection (ICSI) are effective for men with genetic causes of obstructive azoospermia 1
• Genetic counseling should be provided to couples with identified genetic abnormalities to discuss risks to potential offspring 1

Post-Cancer (Convalescent) Infertility

Evaluation and Management

• All male patients undergoing cancer treatment should be offered sperm cryopreservation before starting chemotherapy or radiotherapy 1
• For men who are persistently azoospermic after cancer treatment, microdissection testicular sperm extraction is recommended as a treatment option 1
• There is limited chance of recovery from azoospermia after 10 years following radiotherapy, total body irradiation, or chemotherapy 1

Medical Therapies for Infertility

Hormonal Treatments

• For men with hypogonadotropic hypogonadism, human chorionic gonadotropin (hCG) is the first-line treatment (500-2500 IU, 2-3 times weekly), followed by FSH injections when indicated 1
• Selective estrogen receptor modulators (SERMs) may be considered for men with idiopathic infertility, as they have been shown to significantly increase pregnancy rates and improve sperm and hormonal parameters 1
• Aromatase inhibitors can increase endogenous testosterone production and improve spermatogenesis in infertile men 1
• Exogenous testosterone therapy should NOT be prescribed to men interested in current or future fertility, as it inhibits spermatogenesis 1

Lifestyle Modifications and Supplements

• Weight loss, physical exercise, and smoking cessation can enhance sperm parameters and should be encouraged 1
• Antioxidant therapy may improve live birth rates, though evidence quality is low 1
• Prebiotic/probiotic supplementation has shown promise in improving sperm parameters and DNA integrity in men with idiopathic infertility 1

Surgical Interventions

For Obstructive Azoospermia

• For men with obstructive azoospermia, sperm may be extracted from either the testis or epididymis 1
• Microsurgical reconstruction of the male reproductive tract may be preferable to sperm retrieval and ICSI for acquired or congenital obstruction (excluding CBAVD) when the female partner has normal fertility 1
• For ejaculatory duct obstruction (EDO), transurethral resection of ejaculatory ducts (TURED) or surgical sperm extraction are treatment options 1

For Non-Obstructive Azoospermia (NOA)

• Micro-TESE has been shown to be 1.5 times more effective than conventional TESE for men with NOA 1
• Testosterone deficiency requiring replacement remains a risk even after micro-TESE 1
• Limited data supports pharmacologic manipulation with SERMs, aromatase inhibitors, and gonadotropins prior to surgical intervention for NOA 1

Ejaculatory Dysfunction

• For men with aspermia, options include surgical sperm extraction or induced ejaculation using sympathomimetics, vibratory stimulation, or electroejaculation 1
• Retrograde ejaculation can be treated with sympathomimetics and alkalinization of urine with or without urethral catheterization 1

Assisted Reproductive Technologies (ART)

• For couples with unexplained infertility or when other treatments fail, ART including intrauterine insemination (IUI) or in vitro fertilization (IVF) with ICSI may be necessary 1
• IVF treatment typically allows for a 37% live delivery rate per initiated cycle, with success rates declining with increased female age 1
• For men with obstructive azoospermia, there are no substantial differences in ICSI success rates between cryopreserved and fresh sperm 1
• For men with NOA, some centers perform simultaneous sperm retrieval with ART due to limited sperm numbers and potential cryopreservation challenges 1

Important Considerations

• Male infertility is associated with higher rates of overall health issues, including increased risk of testicular cancer, other cancers, and higher mortality rates 1
• All infertile men should be screened for modifiable cardiovascular risk factors, as they have higher cardiovascular and overall mortality compared to fertile men 1
• Advanced paternal age (≥40) increases risks of adverse health outcomes for offspring, including de novo mutations and genetically-mediated conditions 1
• Treatment decisions should involve shared decision-making between the couple and healthcare providers, considering the specific needs and characteristics of the couple 1