Infertility

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Chapter 170 Infertility

INTRODUCTION

Description: Infertility is the inability to conceive or bear a child despite more than 1 year of trying. Under ordinary circumstances, 80% to 90% of normal couples conceive during 1 year of attempting pregnancy. Infertility may be further subdivided into primary and secondary types based on the patient’s past reproductive history: patients who are infertile and nulligravid are in the primary infertility group and those who have become pregnant more than 1 year previously, regardless of the outcome of that pregnancy, are in the secondary infertility group. Slightly more than one half of patients experiencing infertility fall into the primary group.
Prevalence: Eight percent to eighteen percent of the American population; slightly higher for couples who have never conceived and slightly lower for couples who have conceived before. Roughly 6.1 million women in the United States.
Predominant Age: Reproductive. The prevalence of infertility increases with the age of the woman. Age-related infertility is becoming more common because about 20% of American women delay their attempts at pregnancy to after age 35.
Genetics: No specific genetic pattern. Some chromosomal abnormalities are associated with reduced or absent fertility.

ETIOLOGY AND PATHOGENESIS

Causes: Approximately 35% to 50% of infertility is due to a male factor such as azoospermia. Female factors, such as tubal disease (20% to 30%), ovulation disorders (10% to 15%), and cervical factors (5%), contribute to the roughly 50% to 60% of female causes. The remaining 10% to 20% of couples have no identifiable cause for their infertility (idiopathic). Couples experiencing primary infertility are more likely to have idiopathic or chromosomal causes than are couples who have conceived previously.
Risk Factors: Factors that increase the risk of anovulation (obesity, athletic overtraining, exposure to drugs or toxins), pelvic adhesive disease (infection, surgery, endometriosis), impaired sperm production (mumps, varicocele), or sperm delivery (ejaculatory dysfunction).

CLINICAL CHARACTERISTICS

Signs and Symptoms

Inability to conceive after 1 year of attempts.

DIAGNOSTIC APPROACH

Differential Diagnosis

• Recurrent pregnancy loss
• Primary infertility—chromosomal abnormality (e.g., 45,XO [Turner’s syndrome], 46,XY gonadal dysgenesis [Swyer syndrome], 46,XX q5 X chromosome long-arm deletion)
• Congenital abnormality of the genital tract (either partner)

Associated Conditions: Based on the pathologic condition causing the infertility.

Workup and Evaluation

Laboratory: Based on diagnoses being considered.
Imaging: Based on diagnoses being considered.
Special Tests: Half of all women found to have tubal factor infertility have no history of antecedent infections or surgery, supporting the need to evaluate tubal patency in patients regardless of their past history.
Diagnostic Procedures: Based on diagnoses being considered.

Pathologic Findings

None.

MANAGEMENT AND THERAPY

Nonpharmacologic

General Measures: Support—because infertility involves both members of the couple and intrudes on the most intimate aspects of their relationship, all with no promise of success, a great deal of support is vital.
Specific Measures: The treatment of a couple experiencing infertility is based on identifying the impediment to fertility and overcoming or bypassing it to achieve pregnancy. Most couples can be successfully treated with conventional therapies (e.g., medications or surgery) rather than advanced assisted reproductive technologies. In vitro fertilization techniques account for only about 5% of infertility services and are associated with a roughly 32% live delivery rate per egg retrieval (2004).
Diet: No specific dietary changes indicated.
Activity: No restriction, unless athletic activities are thought to be adversely affecting fertility (exercise-induced amenorrhea). While the evaluation of infertility proceeds, couples should be instructed to continue attempting pregnancy through intercourse timed to the most fertile days of the cycle.
Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP136 (Evaluating Infertility), AP137 (Treating Infertility).

Drug(s) of Choice

(Based on diagnosis of cause.)
Secondary infertility (ovulation induction)—clomiphene citrate 50 mg PO daily on days 5 to 10 of the menstrual cycle; may be increased to 100 mg PO daily on days 5 to 10 of the menstrual cycle if ovulation does not occur. Metformin (1500 mg/day) as an adjunctive treatment for ovulation induction (considered now as first-line therapy for polycystic ovary syndrome).

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Contraindications: Undiagnosed infertility.
Precautions: The possibility of ovarian hyperstimulation must be considered and close follow-up should be maintained if ovulation induction is attempted.

Alternative Drugs

Gonadotropin-releasing hormone (GnRH) agonists may be used to control the hormonal environment during ovulation induction. Human gonadotropins may be used to induce ovulation but are associated with an increased risk of multiple ovulations and multiple gestations if pregnancy ensues.

FOLLOW-UP

Patient Monitoring: Normal health maintenance.
Prevention/Avoidance: None.
Expected Outcome: Less than 40% of couples with primary infertility conceive after 6 years of therapy compared with more than 50% of secondary infertility couples who conceive by 3 years.

MISCELLANEOUS

Pregnancy Considerations: No effect on pregnancy once pregnancy is achieved. Some causes of impaired fertility are associated with a greater risk of early pregnancy loss.
ICD-9-CM Codes: 628.9 (other more specific classifications based on cause).

REFERENCES

Level I

Steures P, van der Steeg JW, Hompes PG, et alCollaborative Effort on the Clinical Evaluation in Reproductive Medicine. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial. Lancet. 2006;368:216.

Level II

Legro RS, Barnhart HX, Schlaff WD, et alCooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551.

Reddy UM, Wapner RJ, Rebar RW, Tasca RJ. Infertility, assisted reproductive technology, and adverse pregnancy outcomes: executive summary of a National Institute of Child Health and Human Development workshop. Obstet Gynecol. 2007;109:967.

Level III

American College of Obstetricians and Gynecologists. Management of infertility caused by ovulatory dysfunction. ACOG Practice Bulletin 34. Obstet Gynecol. 2002;99:347.

American College of Obstetricians and Gynecologists. Adoption. ACOG Committee Opinion 368. Obstet Gynecol. 2007;109:1507.

Bagshawe A, Taylor A. ABC of subfertility. Counselling. BMJ. 2003;327:1038.

Bagshawe A, Taylor A. Intractable infertility. BMJ. 2003;327:1098.

Braude P, Rowell P. Assisted conception. II—In vitro fertilisation and intracytoplasmic sperm injection. BMJ. 2003;327:852.

Braude P, Rowell P. Assisted conception. III—Problems with assisted conception. BMJ. 2003;327:920.

Cahill DJ, Wardle PG. Management of infertility. BMJ. 2002;325:28.

Evers JL. Female subfertility. Lancet. 2002;360:151.

Frey KA, Patel KS. Initial evaluation and management of infertility by the primary care physician. Mayo Clin Proc. 2004;79:1439.

Hamilton-Fairley D, Taylor A. Anovulation. BMJ. 2003;327:546.

Hart R. Unexplained infertility, endometriosis, and fibroids. BMJ. 2003;327:721.

Khalaf Y. ABC of subfertility. Tubal subfertility. BMJ. 2003;327:610.

Makar RS, Toth TL. The evaluation of infertility. Am J Clin Pathol. 2002;117:S95.

Pickering S, Braude P. Further advances and uses of assisted conception technology. BMJ. 2003;327:1156.

Rowell P, Braude P. Assisted conception. I—General principles. BMJ. 2003;327:799.

Setji TL, Brown AJ. Polycystic ovary syndrome: diagnosis and treatment. Am J Med. 2007;120:128.

Smith S, Pfeifer SM, Collins JA. Diagnosis and management of female infertility. JAMA. 2003;290:1767.

Taylor A. ABC of subfertility: extent of the problem. BMJ. 2003;327:434.

Taylor A. ABC of subfertility. Making a diagnosis. BMJ. 2003;327:494.

Van Voorhis BJ. Outcomes from assisted reproductive technology. Obstet Gynecol. 2006;107:183.

Van Voorhis BJ. Clinical practice. In vitro fertilization. N Engl J Med. 2007;356:379.

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Chapter 170 Infertility

INTRODUCTION

Description: Infertility is the inability to conceive or bear a child despite more than 1 year of trying. Under ordinary circumstances, 80% to 90% of normal couples conceive during 1 year of attempting pregnancy. Infertility may be further subdivided into primary and secondary types based on the patient’s past reproductive history: patients who are infertile and nulligravid are in the primary infertility group and those who have become pregnant more than 1 year previously, regardless of the outcome of that pregnancy, are in the secondary infertility group. Slightly more than one half of patients experiencing infertility fall into the primary group.
Prevalence: Eight percent to eighteen percent of the American population; slightly higher for couples who have never conceived and slightly lower for couples who have conceived before. Roughly 6.1 million women in the United States.
Predominant Age: Reproductive. The prevalence of infertility increases with the age of the woman. Age-related infertility is becoming more common because about 20% of American women delay their attempts at pregnancy to after age 35.
Genetics: No specific genetic pattern. Some chromosomal abnormalities are associated with reduced or absent fertility.

ETIOLOGY AND PATHOGENESIS

Causes: Approximately 35% to 50% of infertility is due to a male factor such as azoospermia. Female factors, such as tubal disease (20% to 30%), ovulation disorders (10% to 15%), and cervical factors (5%), contribute to the roughly 50% to 60% of female causes. The remaining 10% to 20% of couples have no identifiable cause for their infertility (idiopathic). Couples experiencing primary infertility are more likely to have idiopathic or chromosomal causes than are couples who have conceived previously.
Risk Factors: Factors that increase the risk of anovulation (obesity, athletic overtraining, exposure to drugs or toxins), pelvic adhesive disease (infection, surgery, endometriosis), impaired sperm production (mumps, varicocele), or sperm delivery (ejaculatory dysfunction).

CLINICAL CHARACTERISTICS

Signs and Symptoms

Inability to conceive after 1 year of attempts.

DIAGNOSTIC APPROACH

Differential Diagnosis

• Recurrent pregnancy loss
• Primary infertility—chromosomal abnormality (e.g., 45,XO [Turner’s syndrome], 46,XY gonadal dysgenesis [Swyer syndrome], 46,XX q5 X chromosome long-arm deletion)
• Congenital abnormality of the genital tract (either partner)

Associated Conditions: Based on the pathologic condition causing the infertility.

Workup and Evaluation

Laboratory: Based on diagnoses being considered.
Imaging: Based on diagnoses being considered.
Special Tests: Half of all women found to have tubal factor infertility have no history of antecedent infections or surgery, supporting the need to evaluate tubal patency in patients regardless of their past history.
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