Infertility
Infertility is failure to conceive after 12 months of regular, unprotected intercourse (6 months if the woman is 35 or older), most often from ovulatory dysfunction, male factor, or tubal or pelvic disease. Diagnosis rests on midluteal progesterone, semen analysis, and hysterosalpingography in both partners concurrently. First-line treatment for anovulatory infertility is ovulation induction with letrozole or clomiphene citrate, escalating to intrauterine insemination or in vitro fertilization when indicated.
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What this article covers
- Overview
Infertility is a couple's failure to conceive despite regular, unprotected intercourse for a defined interval.
- Epidemiology
Infertility affects a substantial share of reproductive-age couples, and declining oocyte quality with maternal age is a major driver, the reason the evaluation threshold shortens after age 35.
- Risk factors
Advanced maternal age: oocyte quality declines after the mid-30s, why evaluation begins after 6 months instead of 12 in women 35 or older.
- Pathophysiology
Ovulation depends on pulsatile hypothalamic gonadotropin-releasing hormone (GnRH) driving pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which mature an ovarian follicle and trigger its release.
- Clinical features
The presenting complaint is failure to conceive: 12 months of regular, unprotected intercourse without pregnancy in a woman younger than 35, or 6 months if 35 or older; pregnancy chance per cycle is…
- Differential diagnosis
Polycystic ovary syndrome: oligomenorrhea, hyperandrogenism, and low midluteal progesterone, but TSH and prolactin are normal, unlike the two mimics below.
- Diagnosis
What establishes the diagnosis: infertility is defined, and evaluation triggered, once a couple fails to conceive after 12 months of regular, unprotected intercourse (or 6 months if the woman is 35…
- Management
First, optimize the basics for every couple: intercourse every 1 to 2 days around the fertile window, and correct reversible findings (weight, smoking, alcohol, thyroid disease, hyperprolactinemia) alongside fertility-specific treatment.
- Complications
Ovarian hyperstimulation, with ovarian enlargement and third-space fluid shift, is the most common complication of clomiphene or gonadotropin-based induction, why ovarian size is monitored during treatment.
- Prognosis
Outcomes depend on the identified cause and, above all, on female age.
- Prevention
Treat sexually transmitted infections promptly: antibiotic treatment of chlamydial cervicitis prevents the ascending pelvic inflammatory disease that scars the fallopian tubes.
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Related articles
- Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder of chronic anovulation and is the most common cause of hirsutism and anovulatory infertility in women. First-line treatment is weight loss for patients with an elevated BMI, combined oral contraceptives for menstrual dysfunction and hirsutism when fertility is not desired, and clomiphene citrate or letrozole for ovulation induction when fertility is desired.
- Hyperprolactinemia
Hyperprolactinemia is an elevated serum prolactin level with causes ranging from physiologic states and medications to hypothyroidism, renal failure, and a prolactin-secreting pituitary tumor. Diagnosis requires a confirmed elevated prolactin with exclusion of pregnancy, medication effect, and hypothyroidism before attributing the finding to a pituitary adenoma, and first-line treatment for a symptomatic pituitary cause is a dopamine agonist such as cabergoline.
- Hypothyroidism
Hypothyroidism is thyroid hormone deficiency, most commonly caused by autoimmune (Hashimoto) thyroid failure in iodine-sufficient countries, diagnosed by an elevated thyroid-stimulating hormone with a low or normal free thyroxine. First-line treatment is levothyroxine dosed at 1.6 mcg/kg lean body weight orally once daily, titrated using thyroid-stimulating hormone rechecked no sooner than 6 weeks after any dose change.
- Male hypogonadism
Male hypogonadism is testicular failure to produce adequate testosterone and sperm, diagnosed with two low 8 AM fasting total testosterone levels plus LH and FSH to localize the defect, and treated with testosterone replacement in men not seeking fertility.
- Klinefelter syndrome
Klinefelter syndrome is a 47,XXY sex chromosome disorder and the most common cause of primary male hypogonadism, occurring in about 1 in 600 live births. Adult men present with tall stature, small firm testes, gynecomastia, and infertility from azoospermia; the diagnosis is confirmed by karyotype showing 47,XXY, and treatment is lifelong testosterone replacement, which does not restore fertility.
- Varicocele
Varicocele is dilation of the pampiniform venous plexus and internal spermatic veins, usually left-sided because of the right-angle insertion of the left gonadal vein into the left renal vein, presenting as a painless, non-transilluminating 'bag of worms' scrotal mass that augments with standing or Valsalva and is a leading cause of male infertility. Diagnosis is clinical, confirmed by scrotal Doppler ultrasound when uncertain, and management is conservative (scrotal support, NSAIDs) for asymptomatic cases without testicular atrophy, escalating to surgical ligation or percutaneous embolization for pain, testicular atrophy, or infertility in a patient desiring fertility.
- Endometriosis
Endometrial-like glands and stroma implanted outside the uterus drive cyclic pelvic pain, dyspareunia, dyschezia, and infertility. Diagnosis is presumed clinically and confirmed by laparoscopic visualization with biopsy; treatment is staged from NSAIDs and hormonal suppression through conservative or definitive surgery.
- Evaluation of secondary amenorrhea
Secondary amenorrhea is absence of menses for 3 months in a woman with prior regular cycles or 6 months with prior irregular cycles, worked up stepwise with beta-hCG, TSH, prolactin, and a progesterone challenge test, then treated with the cause-specific therapy (cyclic progestin, dopamine agonist, thyroid replacement, or estrogen replacement).