Female infertility - Etiology

Author: Dr. Om J Lakhani

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• Q. What is the most common cause of infertility in females?

  • Ovulatory dysfunction

• Q. Enlist some common causes of female infertility?

  • Ovulatory dysfunction
  • Pelvic adhesion
  • Endometriosis
  • Hyperprolactinemia
  • Tubal blockage
  • Other tubal abnormalities
  • Ovarian disorders

• Q. Which females are less likely to have ovulatory dysfunction?

  • Females having regular menses and molimina

• Q. Enlist the causes of ovulatory dysfunction?

  • Primary hypothalamic-pituitary dysfunction
    • Immaturity at onset of menarche or perimenopausal decline
    • Intense exercise
    • Eating disorders
    • Stress
    • Idiopathic hypogonadotropic hypogonadism
    • Hyperprolactinemia
    • Lactational amenorrhea
    • Pituitary adenoma or other pituitary tumors
    • Kallmann's syndrome
    • Tumors, trauma, or radiation of the hypothalamic or pituitary area
    • Sheehan's syndrome
    • Empty sella syndrome
    • Lymphocytic hypophysitis (autoimmune diseases)
  • Other disorders
    • Polycystic ovary syndrome
    • Hyperthyroidism or hypothyroidism
    • Hormone-producing tumors (adrenal, ovarian)
    • Chronic liver or renal disease
    • Cushing's disease
    • Congenital adrenal hyperplasia
    • Premature ovarian failure, which may be autoimmune, genetic, surgical, idiopathic, or related to drugs or radiation
    • Turner syndrome
    • Androgen insensitivity syndrome
  • Medications
    • Estrogen-progestin contraceptives
    • Progestins
    • Antidepressant and antipsychotic drugs
    • Corticosteroids
    • Chemotherapeutic agents

• Q. What are the three WHO classes of anovulation?

  • Class I - Hypogonadotropic hypogonadism
  • Class II - Normogonadotropic normogonadism with anovulation (e.g., PCOS)
  • Class III - Hypergonadotropic hypogonadism (e.g., Primary ovarian insufficiency)

• #Pearl

  • Oocyte aging is an important cause of ovulatory dysfunction in ovaries

• Q. Give the counts of ovarian follicles at various time points?

  • 6-7 million at midgestation
  • 1-2 million at birth
  • 300,000 at puberty

Fallopian tube

• Q. What is the primary cause of tubal infertility or tubal block?

  • Pelvic inflammatory disease (PID) - most common
  • Endometriosis - second most common

• Q. What is hydrosalpinx?

  • Patients with distal tubular obstruction develop hydrosalpinx proximally
  • This reduces the chances of fertility even by IVF

Uterus

• Q. Do uterine fibroids cause infertility?

  • Only submucosal or intracavity fibroids cause infertility
  • This is mainly due to inhibition of implantation

• Q. What uterine anatomical abnormalities lead to infertility?

  • Synechiae from previous uterine procedures
  • Müllerian abnormalities
  • Septate uterus

• Q. What is a Luteal phase defect? Does it cause infertility?

  • It is inadequate production of progesterone by corpus luteum
  • Progesterone is required to prepare the uterine endometrium for implantation
  • However, LPD causing infertility is questioned

Other causes of infertility

• Q. How does endometriosis produce infertility?

  • Formation of pelvic adhesions
  • Damage to the ovary by endometrioma
  • Production of growth factors and cytokines that impair fertility

• Q. Which cervical factors produce infertility?

  • Cervical trauma and anatomical abnormalities of the cervix

• Q. Do autoimmune disorders lead to infertility?

  • Autoimmune disorder per se may not lead to infertility but may be linked with a higher incidence of autoimmune oophoritis and POI
  • APS syndrome can lead to infertility and early pregnancy loss
  • Celiac disease has been linked with infertility

• Q. Do chromosomal abnormalities in women lead to infertility?

  • Yes
  • The chief being Turner syndrome

• Q. Which gene defect specifically affects follicular development?

  • TUBB8 mutation
  • It disrupts microtubular function and therefore arrests oocyte maturation during division

• Q. Summarize the causes of infertility in women?

  • Ovulatory dysfunction
    • Type I - hypogonadotropic hypogonadism
    • Type II - normogonadotropic normogonadism - PCOS
    • Type III - hypergonadotropic hypogonadism - POI
  • Fallopian tube and tubal block
  • Uterine factors
    • Anatomical defects
    • Fibroids
    • Endometriosis
  • Cervical factors
  • Autoimmune causes
  • Chromosomal and genetic factors
  • Lifestyle factors
  • Unexplained infertility