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Tuesday, August 12, 2025

Infertility


Definition

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.

  • Primary infertility: No prior pregnancy

  • Secondary infertility: Difficulty conceiving after at least one previous pregnancy

For women over 35 years of age, evaluation is typically initiated after 6 months due to age-related decline in fertility.

Epidemiology

  • Affects approximately 10–15% of couples globally

  • Female factors contribute to ~40%, male factors to ~30–40%, and combined or unexplained factors to the remainder

Causes

1. Female Factors

  • Ovulatory disorders: Polycystic ovary syndrome (PCOS), hypothalamic amenorrhea, hyperprolactinemia, premature ovarian insufficiency

  • Tubal factors: Pelvic inflammatory disease, tubal surgery, endometriosis

  • Uterine factors: Fibroids, intrauterine adhesions (Asherman’s syndrome), congenital anomalies

  • Cervical factors: Abnormal mucus production, stenosis

2. Male Factors

  • Spermatogenesis defects: Varicocele, genetic abnormalities (Klinefelter syndrome), infections (mumps orchitis), environmental toxins

  • Obstruction: Congenital bilateral absence of the vas deferens, scarring from infection or surgery

  • Endocrine causes: Hypogonadotropic hypogonadism, hyperprolactinemia

  • Sexual dysfunction: Erectile or ejaculatory disorders

3. Combined and Unexplained Infertility

  • Both partners have contributing factors or no identifiable cause is found after standard evaluation

Pathophysiology

Successful conception requires:

  1. Adequate gamete production (sperm and oocytes)

  2. Effective gamete transport through reproductive tracts

  3. Successful fertilization

  4. Implantation in a receptive endometrium
    Disruption at any of these stages can cause infertility.

Evaluation

Female partner

  • Detailed menstrual, obstetric, and medical history

  • Assessment of ovulation (menstrual history, luteal phase progesterone level, ovulation predictor kits)

  • Ovarian reserve testing: Anti-Müllerian hormone (AMH), day 3 FSH and estradiol, antral follicle count on ultrasound

  • Pelvic ultrasound to assess uterus and ovaries

  • Hysterosalpingography (HSG) or sonohysterography to evaluate uterine cavity and tubal patency

  • Laparoscopy if endometriosis or pelvic adhesions are suspected

Male partner

  • Medical and sexual history, lifestyle factors

  • Semen analysis (volume, concentration, motility, morphology)

  • Hormonal evaluation if sperm count is low (FSH, LH, testosterone, prolactin)

  • Scrotal ultrasound for varicocele or structural abnormalities

Both partners

  • Genetic testing if indicated (e.g., karyotyping, CFTR gene mutation in congenital absence of vas deferens)

  • Infectious screening before assisted reproduction

Management

Treatment is tailored to the underlying cause and may involve one or both partners.

1. Lifestyle Modifications

  • Maintain healthy body weight (BMI 18.5–24.9)

  • Stop smoking, alcohol, and illicit drug use

  • Reduce caffeine intake

  • Manage stress and optimize sexual timing (every 2–3 days during fertile window)

2. Medical Treatment for Female Infertility

Ovulation Induction

  • Clomifene citrate: 50–150 mg orally daily for 5 days starting on day 2–5 of cycle; first-line in women with PCOS

  • Letrozole: 2.5–7.5 mg orally daily for 5 days starting on day 2–5; increasingly preferred in PCOS due to higher live birth rates

  • Gonadotropins (FSH, hMG): SC or IM injections with ultrasound and hormone monitoring; risk of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS)

  • Metformin: 500–2000 mg/day orally, especially in insulin-resistant PCOS

Hyperprolactinemia

  • Cabergoline: 0.25–1 mg orally twice weekly

  • Bromocriptine: 1.25–2.5 mg orally once or twice daily

Thyroid Disorders

  • Levothyroxine for hypothyroidism

3. Medical Treatment for Male Infertility

  • Hormonal therapy for hypogonadotropic hypogonadism (e.g., hCG injections 1,500–2,500 IU SC/IM 2–3 times per week ± FSH)

  • Surgery for varicocele repair

  • Surgical correction of obstructive azoospermia or sperm retrieval for assisted reproduction

4. Surgical Treatments in Female Infertility

  • Laparoscopic adhesiolysis for pelvic adhesions

  • Salpingectomy or salpingostomy for tubal disease

  • Hysteroscopic polypectomy or myomectomy for intrauterine lesions

  • Endometriosis excision to restore anatomy and improve fertility

5. Assisted Reproductive Technologies (ART)

  • Intrauterine insemination (IUI): Placement of washed sperm into the uterine cavity around ovulation

  • In vitro fertilization (IVF): Ovarian stimulation, egg retrieval, fertilization in the lab, embryo transfer

  • Intracytoplasmic sperm injection (ICSI): Injection of a single sperm into an egg, used in severe male factor infertility

  • Donor gametes: Egg or sperm donation in cases of absent viable gametes

  • Surrogacy: Gestational carrier for women unable to carry a pregnancy

Prognosis

  • Depends on age, duration of infertility, cause, and treatment type

  • Younger age is associated with higher success rates for all treatments

  • ART success rates vary: IVF live birth rate per cycle ranges from 20–40% depending on age and other factors

Complications of Treatment

  • Multiple pregnancy (especially with ovulation induction and ART)

  • OHSS with gonadotropin therapy

  • Surgical risks from laparoscopy or hysteroscopy

  • Psychological stress and emotional burden




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