Fertility Problems Disease

BASICS

DESCRIPTION

Failure to conceive after one year of unprotected intercourse

  • System(s) affected: Reproductive, Endocrine/Metabolic
  • Genetics:
    PCO; clusters in families. Possibly genetic defects - insulin gene polymorphism, cholesterol side chain cleavage gene regulatory area polymorphism.
  • Incidence/Prevalence in USA:
    10-15% of all couples
  • Predominant age: Increases with age, e.g., ages 30-34: 14% infertile, ages 35-39: 20% infertile, ages 40-45: 25% infertile
  • Predominant sex: N/A
SIGNS AND SYMPTOMS
  • Thorough history and physical should be performed on each partner
  • Genital/pelvic infection (e.g., pelvic inflammatory disease) often associated with an obstruction of reproductive tract
  • Endocrine dysfunction (e.g., hypothyroidism, hypogonadism, abnormal puberty) often associated with abnormalities of ovulation or spermatogenesis
  • Sexual dysfunction (e.g., premature ejaculation) may contribute to the problem
  • Anovulatory cycles are frequently irregular, without premenstrual symptoms nor dysmenorrhea. Some patients may have features (e.g., hirsutism, obesity, acne) suggestive of polycystic ovarian syndrome.
  • Endometriosis is often associated with cyclic premenstrual pain and secondary dysmenorrhea
CAUSES
  • Most couples have more than one factor
  • Male factors 30-40%
  • Ovulation factors 15%
  • Cervical/uterine factors 10%
  • Tubal/peritoneal factors 25-30%
  • Immunologic factors 5%
  • Psychogenic/nutritional/metabolic factors 5%
  • Unexplained infertility 10-20%
RISK FACTORS

Multiple - see under Causes

DIAGNOSIS

LABORATORY
  • Semen analysis, normal values are:
    • Volume 2-6 mL
    • pH 7-8
    • Viscosity - liquefies within one hour
    • Count - 20 million/cc or greater
    • Motility - 50% or more
    • Morphology - 30% or more normal morphology
  • Post coital test
    • Evaluates sperm/cervical mucus interaction
    • Cervical mucus is aspirated with a nasal polyps forceps or a tuberculin syringe from the os after intercourse during the mid cycle (ferning, elasticity of mucus)
    • If 10 or more sperm with directional movement are seen per high-power field of a microscope, the result is good. Sperm with shaking motion suggest sperm antibody.
  • Basal body temperature charting
    • Assesses ovulation and adequacy of the luteal phase
    • Morning temperature should rise about one degree Fahrenheit at the time of ovulation and remain elevated for 13-14 days (less than 11 is abnormal)
  • Serum progesterone
    • Assesses ovulation and corpus luteum function
    • A level of 10 or greater correlates with ovulation
    • Should be obtained on approximately day 21-23 of a 28 day menstrual cycle
  • Endometrial biopsy (short luteal phase, progesterone < 10-15)
    • Obtain on day 25-27 of a 28 day cycle or 10 days after the LH surge
    • Assesses ovulation, function of the corpus luteum, and normalcy of the endometrium (rule out luteal phase defect - out of phase endometrium > 2 days in at least 2 cycles)
  • The following tests are useful to evaluate underlying causes of anovulation or low sperm counts:
    • Thyroid stimulating hormone (TSH) and prolactin (elevations associated with suppressed gonadal function)
    • Testosterone - decreased in primary male gonadal failure; increased in female hyperandrogenism, PCO (Polycystic Ovary Syndrome)
    • Follicle stimulating hormone (FSH) and luteinizing hormone (LH) (elevated in primary gonadal failure, decreased in hypopituitarism); LH/FSH ratio > 2.5 consistent with PCO
    • Karyotype (elevated FSH/LH), e.g., Klinefelter's syndrome, Turner's syndrome (mosaic)
    • Glucose intolerance - glucose tolerance test, fasting glucose/insulin ratio 20 µU/cc - insulin resistance, PCO
    • Late onset congenital adrenal hyperplasia - 17 OH progesterone
    • Adrenal disease - DHEAS (Dehydroepiandrosterone sulfate)
Drugs that may alter lab results:
  • Semen abnormalities can be caused by:
    • Cimetidine
    • Spironolactone
    • Nitrofurantoin
    • Sulfasalazine
    • Marijuana
    • Chemotherapeutic agents
    • Cocaine
    • Excessive alcohol
    • Occupational/environmental hazards
Disorders that may alter lab results:
  • Polycystic ovarian disease (PCOD)
  • Endometriosis
  • Severe hypospadias
  • Retrograde ejaculation (often associated with diabetes)
  • Varicocele
  • Testicular injury (e.g., surgery, mumps, trauma)
  • Occupational/environmental hazards
PATHOLOGICAL FINDINGS
N/A
SPECIAL TESTS
Multiple tests (e.g., hamster egg penetration assay - to assess sperm's ability to fertilize) are available to study specific aspects of reproduction, but are used only by fertility specialists, and available in only specialized labs. Also hemizona assay, immunobead binding test.
IMAGING
  • Hysterosalpingogram (HSG) - evaluates tubal patency and uterine contour. This procedure may have some therapeutic benefit. Avoid if history suggests an infection.
  • Pelvic ultrasound - fibroids, ovarian pathology, endometriomas, subcortical ovarian cysts (PCO)
  • MRI - Müllerian defects
DIAGNOSTIC PROCEDURES
Laparoscopy - should be deferred until basic evaluation is complete. Can be diagnostic and therapeutic (eg, chromotubation, simultaneous hysteroscopy and operative laparoscopy). Ovarian drilling in clomiphene resistant PCO.

TREATMENT

APPROPRIATE HEALTH CARE

Outpatient evaluation, with attention to the emotional support of the couple

GENERAL MEASURES
  • Dispel myths and provide accurate information
  • Simultaneously evaluate and counsel both partners
  • Find and correct causes of infertility
  • Provide information on adoption when appropriate. Preferably early in work-up than later
  • Consider donor insemination or intrauterine insemination for refractory abnormalities of semen analysis. Intracytoplasmic sperm injection (ICSI) available for oligospermia, antisperm antibodies, poor cervical mucus, or poor capacitation.
  • Discontinue bad habits, smoking, excessive alcohol, and/or illicit drugs
  • IVF (In Vitro Fertilization) - indicated for severe tubal disease, need for donor eggs, or sperm manipulation. IVF is indicated after 2 years of unexplained infertility, after 1 year of treatment for a particular defect, or after 1 year of donor insemination or ovulation induction.
  • Unexplained infertility - superovulation, with or without intrauterine insemination
SURGICAL MEASURES
  • Consider varicocele repair for abnormal semen analysis
  • Consider laparotomy for tubal factor, lysis of adhesions, and correction of tubal obstruction
  • Correction of Müllerian defects
  • Removal of polyps, fibroids (only after other factors ruled out)
ACTIVITY
  • Males with low sperm counts should avoid hot tubs/saunas (decreased spermatogenesis with elevated scrotal temperature).
  • If the male has low sperm counts, intercourse should be timed to occur approximately every 36 hours during the fertile period. Delay of intercourse beyond 7 days also adversely affects semen quality.
  • Pregnancy rate of 30% if intercourse on day of ovulation, less if several days before, and zero if intercourse after ovulation.
DIET

N/A

PATIENT EDUCATION
  • RESOLVE, 5 Water St, Arlington, MA 02174
  • Fertility Research Foundation, 1430 Second Avenue, Suite 103, New York, NY 10021, (212)744-5500
  • American College of Obstetricians & Gynecologists, 409 12th St, SW, Washington, DC 20024-2188, (800)762-ACOG

FOLLOW UP

PREVENTION/AVOIDANCE
  • Maintain normal BMI
  • Prevention of sexually transmitted disease and subsequent pelvic inflammatory disease
  • Treat endometriosis when diagnosis is made - chronic condition
POSSIBLE COMPLICATIONS
  • Plural gestation with ovulation induction
  • Ectopic pregnancy following tubal re-anastomosis - 15% risk
  • Unsubstantiated risk of ovarian cancer with 11 cycles or more of clomiphene
EXPECTED COURSE AND PROGNOSIS
  • About half of couples conceive during the second year of unprotected intercourse
  • If the couple has been infertile for four or more years, the prognosis tends to be poor
  • Encourage initiation of adoption process

MISCELLANEOUS

ASSOCIATED CONDITIONS

Increasing tubal damage associated with pelvic inflammatory disease and IUD use

AGE-RELATED FACTORS
  • Increasing anovulation with increasing age
  • Increased disease burden with age from diseases like endometriosis, and cumulative exposure to environmental/occupational hazards
  • Decreased ovarian reserve - menstrual day 3 FSH. If > 25, poor reserve. If < 9, adequate reserve. Good IVF candidate.
  • Unruptured luteinized follicle - avoid NSAIDs

Pediatric: N/A
Geriatric: N/A
Others: N/A

PREGNANCY

N/A

OTHER NOTES

N/A

ABBREVIATIONS

N/A

Clinical Investigations
  • Cardiology
  • Dermatology
  • General Destistry
  • Cardiology
  • Dermatology

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