Infertility

Alan H. DeCherney, M.D.
University of California, Los Angeles, UCLA School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Inability to conceive after 1 or more years of regular coital activity without contraception
• Affects nearly 10% of all couples in the United States
• Male infertility in ~ 35%
• Female pelvic factors in ~ 35%
• Abnormal cervical mucus in 5% to 10%
• Ovulatory dysfunction in 15%
• Unexplained infertility in 15% to 20%

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Differential Diagnosis

• Idiopathic oligospermia
• Advanced age
• Testicular injury
• Trauma
• Infection
• Surgery
• Radiation
• Chemotherapy
• Penile and testicular anomalies
• Hypospadia
• Cryptorchidism
• Varicocele

• Advanced age
• Tubal and pelvic factors
• Sexually transmitted disease
• Pelvic inflammatory disease
• Appendicitis with rupture
• Pelvic tuberculosis
• Adnexal surgery
• Endometriosis
• Ectopic pregnancy
• Submucous myomas
• Cervical factors
• Abnormal cervical mucus
• Ovulatory factors
Oligo-ovulation
• Anovulation
• Hypothyroidism
• Pituitary adenoma
• Polycystic ovary syndrome
• Cushing syndrome
• Androgen tumor
• Congenital adrenal hyperplasia (late onset)
• Anorexia
• Stress
• Exercise
• Ovarian failure
• Resistant ovary syndrome

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Best Tests

• Semen analysis
• Sperm penetration assay
• Immunobead-binding assay
• Urology evaluation if semen analysis is persistently abnormal

• Uterine, tubal, or pelvic abnormality
• Hysterosalpingography (HSG)
• Laparoscopy with chromotubation
• Indicated for patients with abnormal HSG
• Cervical factors
• Postcoital cervical mucus examination
• Ovulatory factors
• Basal body temperature chart
• Serum progesterone
• Measurement on day 21 of menstrual cycle
• Provides indirect assessment of ovulatory status
• Endometrial biopsy
• Can be performed on cycle days 23 to 26
• Assesses ovulatory status, luteal phase adequacy
• Anovulation
• Serum prolactin
• Thyroid-stimulating hormone (TSH)
Evaluate if prolactin elevated, with or without galactorrhea
• Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol
• Evaluate if patient is found to be hypoestrogenic on initial exam
• Identifies hypogonadotropic hypogonadism, ovarian failure
• Gonadotropin-releasing hormone stimulation test
• Determine whether hypogonadotropic hypogonadism is reversible
• Serum dehydroepiandrosterone sulfate (DHEAS), total testosterone, 17-hydroxyprogesterone, 8 A.M. free urine cortisol
• Hyperandrogenism, virilization on physical exam
• Polycystic ovary syndrome
• Ovarian and adrenal neoplasms
• Congenital adrenal hyperplasia
• Cushing syndrome
• CT/MRI of head
• Indicated if prolactin elevated and TSH normal

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Best Therapy

• Tubal surgery
• Selective tubal cannulation: proximal tubal occlusion
• Corrective tubal surgery: distal tubal occlusion
• Intrauterine insemination (IUI)
• Cervical factor infertility
• Ovulation induction with clomiphene citrate or gonadotropins
• Anovulation not corrected by treatment specific to cause
• Unexplained infertility; combined with IUI
• Progesterone supplementation after ovulation
• Luteal-phase defect
• In vitro fertilization
• Male infertility
• Tubal occlusion (proximal, distal, or combined)
• Ovarian failure
• Resistant ovary syndrome
• Unexplained infertility not responsive to ovulation induction for 6 mo ± IUI

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Best References

ACOG Practice Bulletin: Obstet Gynecol 99:347, 2002 [PMID 11814521]

Colao A, et al: Ann Med 30:452, 1998 [PMID 9814831]

Guzick DS, et al: Fertil Steril 70:207, 1998 [PMID 9696208]

Keck C, et al: Int J Androl 20(suppl 3):55, 1997 [PMID 9466187]

Kousta E, et al: Hum Reprod Update 3:359, 1997 [PMID 9459281]

October 2006