Gynecology Topic 10. Causes of infertility. The infertile couple

I. Definition and Basic Concepts

Definition

• Infertility: inability of a couple to conceive after 12 months of regular unprotected intercourse.
• Older/classic wording: inability to conceive after 1-2 years despite regular intercourse without contraception.
• Evaluate earlier if female age ≥35 years, irregular menses, known tubal/uterine/ovarian disease, or clear male risk factor.

Types

• Primary infertility: no previous conception/pregnancy.
• Secondary infertility: previous conception/pregnancy, now unable to conceive for >= 12 months.

Chance of Spontaneous Conception

• Within 1 year: about 80-85% conceive.
• Within 2 years: about 90% conceive.

Cause Distribution

• Female factor: about 30%.
• Male factor: about 30%.
• Mixed male + female factor: about 30%.
• Unexplained infertility: about 10%.
• Rule: infertility is a couple diagnosis → evaluate both partners, not only the woman.

II. Female Causes of Infertility

Ovulatory / Endocrine Disorders

1. Central: hypogonadotropic hypogonadism

• Hypothalamic-pituitary insufficiency, stress, weight loss, excessive exercise, eating disorder.
• Hyperprolactinemia: prolactin inhibits GnRH release → anovulation; cause may be pituitary adenoma/prolactinoma.
• Corpus luteum insufficiency / luteal dysfunction: inadequate progesterone support after ovulation.
• PCOS: chronic anovulation + hyperandrogenism; common ovulatory cause.

2. Peripheral: hypergonadotropic hypogonadism

• Premature ovarian insufficiency/failure: loss of ovarian function before age 40.
• Turner syndrome / gonadal dysgenesis.
• Resistant ovary syndrome.
• Ovarian tumors or ovarian damage after surgery/chemotherapy/radiotherapy.

3. Metabolic / systemic causes

• Thyroid disease: hypo- or hyperthyroidism.
• Hepatic disease, diabetes, renal disease.
• Pathologic obesity or severe undernutrition.
• Hyperandrogenic disorders: adrenal/ovarian androgen-secreting tumor, congenital adrenal hyperplasia.

Anatomical Female Factors

• Cervical factor: cervical stenosis, cervicitis, abnormal cervical mucus.
• Uterine/corpus factor: malformation, submucosal leiomyoma, endometrial polyp, adenomyosis.
• Intrauterine adhesions: Asherman syndrome after curettage/infection → impaired implantation.
• Fallopian tube factor: PID, chlamydia/gonorrhea sequelae, endometriosis, tubal scarring/adhesions, previous ectopic pregnancy or tubal surgery.
• Peritoneal factor: pelvic adhesions and endometriosis → impaired oocyte pickup/tubal mobility.

III. Male Causes of Infertility

Pretesticular / Central Causes

• Hypogonadotropic hypogonadism: hypothalamic-pituitary disorder → impaired testicular stimulation.
• Hyperprolactinemia: inhibits GnRH → low testosterone and impaired spermatogenesis/libido.
• Chromosomal disorder: Klinefelter syndrome.
• Erectile dysfunction, ejaculatory dysfunction, psychogenic or organic causes.

Testicular Causes

• Congenital/developmental: cryptorchidism, testicular dysgenesis.
• Genetic/motility disorders: immotile cilia syndrome.
• Infection/inflammation: orchitis.
• Vascular/temperature: varicocele, testicular torsion, heat exposure.
• Antispermatogenic/gonadotoxic agents: chemotherapy, radiotherapy, drugs, toxins.

Posttesticular / Sperm Delivery Causes

• Epididymal or vas deferens obstruction.
• Epididymitis with scarring.
• Previous vasectomy, hernia repair, pelvic surgery or trauma.

IV. The Infertile Couple: First Approach

Basic Advice

• Intercourse timing: fertile window = 6 days before ovulation, especially 2-3 days before ovulation.
• Frequency: intercourse every 1-2 days during fertile window.
• Ovulation prediction: LH urine kits; basal body temperature confirms ovulation retrospectively.
• Lifestyle: stop smoking, avoid excess alcohol/caffeine, optimize BMI, avoid recreational drugs and heat exposure to testes.
• Folic acid: start preconception supplementation in the woman.

When to Start Evaluation

• After 12 months: woman <35 years, regular cycles, no known risk factors.
• After 6 months: woman ≥35 years.
• Immediately/early: woman ≥40 years, amenorrhea/oligomenorrhea, known tubal/uterine disease, endometriosis, recurrent pregnancy loss, previous chemotherapy, or known male subfertility.

Principles of Evaluation

• Evaluate both partners in parallel.
• Male first-line test: semen analysis.
• Female first-line questions: ovulation, ovarian reserve/age, tubal patency, uterine cavity, endometriosis/peritoneal disease.