What fertility evaluation and treatment options are recommended for a patient with impaired fertility, considering their medical history and potential underlying conditions?

Fertibiome: Comprehensive Fertility Evaluation and Treatment

Initial Evaluation Requirements

All couples with impaired fertility require immediate concurrent evaluation of both partners, including a detailed reproductive history, physical examination by a trained examiner, and at minimum two semen analyses separated by 2-3 months for the male partner. 1, 2

Male Partner Evaluation

Reproductive history must document:

• Coital frequency and timing, duration of infertility, and previous fertility 3, 2
• Childhood illnesses, developmental history, and systemic medical conditions (diabetes, respiratory diseases) 3
• Previous surgeries, current medications, allergies, and sexual history including sexually transmitted infections 3
• Gonadotoxin exposures including anabolic steroids, environmental toxins, chemical exposures, and heat sources 3, 1

Physical examination must assess:

• Testicular size and consistency (normal lower limit 15 mL; volumes below this suggest testicular dysfunction) 4, 2
• Presence and consistency of vas deferens bilaterally 2
• Varicocele detection (affects sperm production and quality) 1
• Epididymal abnormalities and secondary sexual characteristics 2

This comprehensive physical examination should be performed initially, not deferred until after abnormal semen results, as limiting assessment to history and semen analysis alone misses significant medical conditions in 0.16% of men with normal semen parameters. 3, 2

Semen Analysis Protocol

Two semen analyses are mandatory, separated by at least one month (preferably 2-3 months), with each sample collected after 2-3 days of abstinence. 1, 2

Assessment must include:

• Sperm concentration (reference: ≥16 million/mL) 4
• Total sperm count (reference: ≥39 million total) 4
• Motility assessment (reference: ≥40% progressive + non-progressive) 1, 4
• Morphology evaluation (reference: ≥3% normal forms) 4
• Semen volume (reference: 1.5-6 mL) and pH 4, 2

Hormonal Evaluation Indications

Endocrine testing including FSH and testosterone is required for:

• Any abnormal semen parameters, particularly sperm concentration <10 million/mL 3, 2
• Impaired sexual function 3
• Clinical findings suggesting endocrinopathy 3
• Testicular volumes below 15 mL 4

When FSH is borderline elevated, immediately measure serum LH and prolactin to distinguish primary testicular dysfunction (elevated LH) from secondary hypogonadism (low/normal LH). 4

If LH is low or low-normal with testosterone <150 ng/dL, obtain pituitary MRI regardless of prolactin level to exclude non-secreting adenomas. 4

Genetic Testing Requirements

Mandatory karyotyping and Y-chromosome microdeletion analysis before considering intracytoplasmic sperm injection (ICSI) for:

• Azoospermia or severe oligospermia <5 million/mL 1, 2
• Non-obstructive azoospermia 2
• Congenital bilateral absence of vas deferens 2

Treatment Options Based on Diagnosis

Hypogonadotropic Hypogonadism

Evaluate to determine etiology and treat based on diagnosis. 3

Clinicians may use aromatase inhibitors, human chorionic gonadotropin (hCG), selective estrogen receptor modulators (SERMs), or combinations thereof for infertile men with low serum testosterone. 3

Testosterone monotherapy is absolutely contraindicated for males interested in current or future fertility, as it suppresses spermatogenesis. 3, 4

Idiopathic Infertility

For men with idiopathic infertility, treatment using FSH analogues may be considered to improve sperm concentration, pregnancy rate, and live birth rate. 3

SERMs have limited benefits relative to assisted reproductive technology (ART) results. 3

Supplements including antioxidants and vitamins are of questionable clinical utility; existing data are inadequate to recommend specific agents. 3

Ovulatory Dysfunction in Female Partners

Clomiphene citrate dosing protocol: 5

• Start with 50 mg daily for 5 days beginning on cycle day 5 5
• If ovulation does not occur after the first course, increase to 100 mg daily for 5 days 5
• Increasing dosage or duration beyond 100 mg/day for 5 days is not recommended 5
• If ovulation does not occur after three courses, further clomiphene treatment is not recommended and the patient requires reevaluation 5
• Long-term cyclic therapy is not recommended beyond approximately six cycles 5

Obstructive Azoospermia

For post-vasectomy patients, both sperm retrieval with ART and microsurgical reconstruction are options, with microsurgical reconstruction preferable when the female partner has normal fertility potential. 3

For ejaculatory duct obstruction, transurethral resection of ejaculatory ducts (TURED) or surgical sperm extraction may be considered. 3

Low Total Motile Sperm Count

Couples with low total motile sperm count on repeated semen analysis should be advised that intrauterine insemination (IUI) success rates may be reduced, and treatment with ART (IVF/ICSI) should be considered. 3

ICSI applied during IVF abrogates adverse effects of sperm number and quality on treatment outcomes. 3

Specialist Referral Criteria

Any abnormal semen parameters require referral to a male reproductive specialist for complete evaluation. 1

Immediate referral is warranted for:

• Sperm concentration <10 million/mL requiring endocrine evaluation and possible genetic testing 1
• FSH remaining >10 IU/L after addressing reversible factors 4
• Azoospermia requiring determination of obstructive versus non-obstructive etiology 3

Critical Health Implications Beyond Fertility

Men with abnormal semen parameters have significantly higher rates of testicular cancer and overall mortality compared to fertile men. 1, 2

Over 50% of male infertility cases stem from specific medical conditions with health implications beyond fertility, making thorough evaluation critical for the patient's overall health. 1

Infertile men have more comorbidities than fertile controls, making this evaluation important for overall health screening. 2

Lifestyle Optimization

Avoid tobacco, limit alcohol consumption, and avoid recreational drugs. 4

Maintain healthy weight with BMI between 18.5-25. 4

Avoid gonadal toxins including heat exposure from hot tubs or saunas, as heat damages spermatogenesis. 4

Limit caffeine to less than 5 cups per day. 4

Follow-Up Monitoring

For men with borderline FSH but currently normal sperm parameters, repeat semen analysis and hormonal evaluation in 1-2 years before attempting conception, as borderline FSH may indicate progressive decline over time. 4