What is the treatment protocol for infertility?

Treatment Protocol for Infertility

The treatment of infertility requires concurrent assessment of both partners, with specific interventions based on identified causes, including correctable conditions, irreversible conditions amenable to assisted reproductive technologies (ART), or conditions requiring donor gametes. 1

Initial Evaluation

Male Partner Assessment

• Reproductive history (mandatory) 1
• Semen analysis (one or more samples) 1
  • Normal parameters: volume 1.5-5.0 mL, pH >7.2, concentration >20 million/mL, total motile count >5 million 2
• Hormonal evaluation for abnormal semen parameters:
  • FSH, LH, testosterone levels 2
  • Elevated FSH (>7.5 IU/L) indicates 5-13 times higher risk of abnormal semen quality 2
• Physical examination by male reproductive specialist for abnormal parameters 1
• Imaging (ultrasound with Doppler) for scrotal evaluation when indicated 2

Female Partner Assessment

• Ovulatory function assessment (serum progesterone at cycle day 21) 3
• Uterine and tubal evaluation via hysterosalpingography or ultrasound 4
• Advanced imaging (laparoscopy, hysteroscopy, MRI) for suspected endometriosis, fibroids, or pelvic infection 4

Treatment Protocols by Diagnosis

1. Male Factor Infertility

Hypogonadotropic Hypogonadism

• First-line therapy: hCG injections (500-2500 IU, 2-3 times weekly) 2, 5
• Add FSH injections after testosterone normalization if needed 1
• Avoid testosterone monotherapy as it suppresses spermatogenesis 1, 2

Idiopathic Oligospermia/Abnormal Semen Parameters

• SERMs (e.g., clomiphene citrate) to stimulate GnRH secretion 2
  • Note: FDA label states "no adequate studies demonstrate effectiveness in male infertility" 6
• Aromatase inhibitors for men with low testosterone 2
• FSH analogues for improving sperm concentration and pregnancy rates 1, 2
• Antioxidant therapy for mild to moderate asthenozoospermia 2
  • Reassess with semen analysis after 3 months 2

Non-Obstructive Azoospermia (NOA)

• Microdissection testicular sperm extraction (micro-TESE) offers best chance (55-56% success rate) 2
• Limited evidence supports pharmacologic manipulation with SERMs, aromatase inhibitors, or gonadotropins prior to surgical intervention 1

Obstructive Azoospermia

• Microsurgical reconstruction for acquired or congenital obstruction (excluding CBAVD) 1
• Surgical sperm extraction (TESE, TESA) for use with ART 1

Ejaculatory Duct Obstruction

• Transurethral resection of ejaculatory ducts (TURED) if confirmed by imaging 1
• Surgical sperm extraction as alternative 1

Ejaculatory Dysfunction

• Sympathomimetics and alkalinization of urine with/without urethral catheterization 1
• Induced ejaculation (vibratory stimulation, electroejaculation) 1
• Surgical sperm extraction if other methods fail 1

2. Female Factor Infertility

Ovulatory Dysfunction

• Clomiphene citrate or letrozole (aromatase inhibitor) for ovulation induction 7, 4
• Gonadotropins for women who fail to respond to first-line agents 7
  • Risks include multiple pregnancy (up to 36%) and ovarian hyperstimulation syndrome (1-5%) 7

Tubal Disease

• Surgical correction for appropriate candidates 4
• IVF for severe tubal disease 7, 4

3. Unexplained Infertility

• Initial approach: 3-4 cycles of ovarian stimulation with timed intercourse 7
• Progress to IVF if initial approach fails 7
• Consider immediate IVF for women >38-40 years due to declining fertility with age 7

Assisted Reproductive Technologies

Intrauterine Insemination (IUI)

• Limited success with low total motile sperm count (<5 million motile sperm after processing) 1
• Consider for mild male factor, unexplained infertility, or mild endometriosis 7, 4

In Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI)

• IVF indicated for severe male factor, bilateral tubal factor, or women >38-40 years 7
• ICSI recommended for severe male factor infertility 1
• Success rates: approximately 37% live delivery rate per initiated IVF cycle 1
• Success decreases with female age over 35 years 1

Important Considerations

• Lifestyle modifications can improve fertility outcomes:

  • Weight management for obesity
  • Smoking cessation
  • Moderate alcohol consumption
  • Avoiding excessive testicular heat exposure 2

• Sperm DNA fragmentation may require testicular sperm retrieval in non-azoospermic males 1

• Recurrent pregnancy loss (two or more losses) warrants male evaluation 1

• Sperm banking before gonadotoxic treatments is crucial for fertility preservation 2