What is the pathophysiology, causes, risk factors, and associated conditions of female infertility?

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Last updated: June 23, 2025View editorial policy

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From the Guidelines

Female infertility is a complex condition characterized by the inability to conceive after 12 months of regular unprotected intercourse, with the pathophysiology primarily involving disruptions in ovulation, fallopian tube function, or uterine receptivity, as noted in the most recent study 1. The causes of female infertility can be broadly categorized into ovulatory disorders, tubal factors, and uterine factors. Ovulatory disorders, such as polycystic ovary syndrome (PCOS), account for approximately 21% of cases, as reported in the study 1. PCOS is a hormonal disorder that causes irregular or absent ovulation, and it affects at least 7% of adult women, according to the study 1. Tubal factors, including blockage or damage to the fallopian tubes, contribute to about 14% of cases, often resulting from pelvic inflammatory disease, endometriosis, or previous abdominal surgeries, as mentioned in the study 1. Uterine factors, such as structural abnormalities like fibroids, polyps, or congenital malformations, can also interfere with implantation.

Some of the key risk factors for female infertility include:

  • Advanced age, particularly over 35, as the quality of oocytes deteriorates with increasing maternal age, as noted in the study 1
  • Obesity, which can disrupt ovulation and increase the risk of infertility, as reported in the study 1
  • Smoking, excessive alcohol consumption, and extreme weight fluctuations, which can also negatively impact fertility
  • History of pelvic infection or surgery, which can lead to the development of intrauterine synechiae, fallopian tube abnormalities, and peritubular adhesions, as mentioned in the study 1

Associated conditions that can contribute to female infertility include:

  • Endometriosis, which affects at least one-third of women with infertility and up to 10% of reproductive-aged women, as reported in the study 1
  • PCOS, which affects at least 7% of adult women, according to the study 1
  • Thyroid disorders, premature ovarian insufficiency, and hyperprolactinemia, which can also impact fertility
  • Unexplained infertility, where no specific cause is identified despite thorough evaluation, accounts for approximately 20-30% of cases, as noted in the study 1.

The most effective approach to managing female infertility involves a comprehensive evaluation to identify the underlying cause, followed by targeted treatment, which may include ovulation induction medications, surgical interventions, or assisted reproductive technologies, as supported by the study 1.

From the Research

Pathophysiology of Female Infertility

The pathophysiology of female infertility is complex and multifactorial. It is estimated that 8-12% of reproductive-aged couples worldwide experience infertility, with females being solely responsible for 20-30% of cases and contributing to 50% of cases overall 2. The spontaneous probability of conception is influenced by three major factors: the time of unwanted non-conception, the age of the female partner, and disease-related infertility.

Causes of Female Infertility

Some causes of female infertility include:

  • Premature ovarian insufficiency
  • Polycystic ovary syndrome (PCOS)
  • Endometriosis
  • Uterine fibroids
  • Endometrial polyps
  • Reproductive tract infections
  • Hypogonadotrophic hypogonadism
  • Hyperprolactinemia
  • Disorders of ciliary function
  • Cystic fibrosis
  • Infections
  • Systemic diseases
  • Lifestyle-related factors/diseases 2, 3

Risk Factors for Female Infertility

Risk factors for female infertility include:

  • Age: The fertility decline in females starts around 25-30 years of age, and the median age at last birth is 40-41 years in most studied populations experiencing natural fertility 2
  • Lifestyle factors:
    • Cigarette smoking
    • Alcohol consumption
    • Caffeine consumption
    • Physical exercise
    • Body mass index (BMI)
    • Drug use 3, 4
  • Environmental toxin exposures
  • Psychological stress

Associated Conditions

Female infertility is associated with several conditions, including:

  • PCOS: A common cause of female infertility, with first-line treatment being oral clomiphene citrate or letrozole 5
  • Endometriosis: A condition characterized by the growth of endometrial tissue outside the uterus, which can lead to infertility
  • Uterine fibroids: Non-cancerous growths in the uterus that can affect fertility
  • Endometrial polyps: Growths in the lining of the uterus that can affect fertility
  • Reproductive tract infections: Infections that can cause scarring and adhesions in the reproductive tract, leading to infertility 2
  • Early mortality: Infertility may be a marker of future health risk in women, including early mortality 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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