SOAP. – Infertility – SỔ TAY LÂM SÀNG

Infertility

Jordan Vaughan and Rhonda Authur

Definition

A.Infertility is defined as the inability of a couple to conceive within 12 months of unprotected intercourse. Many clinicians use a 6-month time frame if the woman is 35 years of age and older due to the age-related decline in fertility. Expedited evaluation may also be considered in situations including oligomenorrhea or amenorrhea, known tubal or uterine disease, endometriosis, or suspected male subfertility.

B.A woman who has never been pregnant or a man who has never initiated a pregnancy is said to have primary infertility.

C.If a previous pregnancy has been achieved and the couple is unable to conceive a subsequent pregnancy, the term secondary infertility is applied.

Incidence

A.It is estimated that approximately one in eight couples have trouble getting pregnant or staying pregnant; 7.4 million, or 12%, of women have received infertility services in their lifetime. The most common cause of female infertility is ovulatory dysfunction. Other common causes include blocked fallopian tubes caused by pelvic inflammatory disease (PID) or endometriosis. The most common cause of male factor infertility is oligospermia (few sperm seen in the ejaculate) or azoospermia (no sperm seen in the ejaculate).

Pathogenesis

Infertility may occur in the male or female. Every effort should be made to evaluate both partners at the same time. Approximately one-third of infertility is attributed to the female, one-third attributed to the male, and the remaining third is due to a combination of factors in both partners. Up to 20% of the time infertility is unexplained:

A.Infrequent intercourse.

B.Medical (see Table 17.3).

Predisposing Factors

A.Predisposing factors depend on the etiology.

Common Complaints

A.The common complaint is an inability to achieve pregnancy despite frequent acts of intercourse.

Other Signs and Symptoms

A.Dependent on the pathogenesis and history.

Subjective Data

A.Obtain a complete health history, including the following:

1.Age of both partners.

2.General health of both partners: past surgeries, previous hospitalizations, serious illnesses or injuries, PID, or exposure to sexually transmitted infections (STIs).

3.Complete pregnancy history of the female:

a.Complications during pregnancy, including placenta previa accreta, gestational diabetes, preterm labor, or cerclage for incompetent cervix.

TABLE 17.3 Pathogenesis of Infertility

A.Inadequate sperm production 1.Azoospermia from: a.Cancer therapy b.Adult mumps c.Sertoli-cell-only syndrome d.Hypogonadism e.Retrograde ejaculation 2.Oligospermia from: a.Varicocele b.Small testicular size B.Reproductive tract anomaly 1.Blocked vas deferens 2.Varicocele 3.Congenital obstruction of epididymis 4.Absence of the vas deferens (cystic fibrosis) C.Klinefelter’s syndrome D.Physical and chemical agent exposure 1.Coal tar 2.Radiation E.Health conditions/disorders 1.Diabetes 2.Low serum testosterone 3.Pituitary tumors 4.Hyperprolactinemia 5.Hypertension F.Testicular infection (epididymitis) G.Injury to reproductive organs/tract H.Nerve damage/neurologic disease: spinal cord injury I.Impotence/erectile difficulty: performance anxiety J.Premature ejaculation K.Early withdrawal L.Lifestyle factors 1.Drugs 2.Smoking 3.Alcohol 4.Malnutrition M.Antispermatozoa antibodies N.Medications 1.Antihypertensives 2.Antidepressants 3.Antipsychotics 4.Antiulcer agents/antacids 5.Muscle relaxants 6.Testosterone 7.Anabolic steroid use

A.Advanced maternal age B.Disorder of ovulation/hypothalamic dysfunction 1.Anovulation 2.Amenorrhea 3.Polycystic ovary triad a.Acne b.Obesity c.Hirsutism 4.Premature ovarian failure a.Autoimmune b.Idiopathic c.Cancer therapy 5.Luteal phase insufficiency 6.Hyperprolactinemia C.Ovarian factors 1.Cysts or tumor 2.Irradiation D.Tubal disorders/damage/blockage 1.PID 2.Chlamydia trachomatis 3.Postpartum infection 4.Pelvic trauma (motor vehicle accident) 5.Inflammatory bowel disease 6.Endometriosis 7.Pelvic adhesions 8.Idiopathic E.Uterine pathology 1.Congenital anomalies: duplication 2.Septate 3.Fibroids 4.Polyps 5.Asherman’s syndrome 6.Synechiae F.Cervical factors 1.Anatomic abnormalities (hood) 2.Previous cervical surgery (i.e., conization, which leads to mucus depletion) 3.Hostile cervical mucus 4.Presence of sperm antibodies in the cervix 5.Infections G.Lifestyle factors 6.Drugs 7.Smoking 8.Alcohol consumption H.Vaginal factors 1.Intact hymen 2.Septum 3.Absent vagina 4.Infection a.Trichomonas b.Candida c.Chlamydia d.Mycoplasma e.Bacterial vaginosis f.Gonorrhea g.Streptococci I.Medications: Oral contraceptives J.Medical problems 1.Lupus 2.Hypothyroidism 3.Diabetes 4.Antiphospholipid syndrome

b.Number of pregnancies, cesarean/vaginal deliveries, miscarriages, dilatation and curettages (D&Cs), abortions.

4.Family history of birth defects, developmental delay, early menopause, or reproductive problems.

5.Length of infertility, including prior workup, if any.

6.Coital history:

a.Frequency and timing.

b.Able to ejaculate in the vagina.

c.Use of lubricants (some may be spermicidal).

d.Postcoital habits: douching or voiding.

B.Obtain a complete menstrual history, including the following:

1.Age at puberty.

2.Cycle length and characteristics.

3.Dysmenorrhea.

4.Molimina.

5.Date of last missed period (LMP).

C.Obtain a complete gynecologic history, including the following:

1.Previous contraceptive use.

2.Medical and surgical interventions:

a.D&C.

b.Laparoscopy or endometriosis.

3.Anomalies.

D.Take a complete nutritional and exercise history; note eating disorders:

1.Anorexia nervosa.

2.Bulimia.

E.Review female and male reproductive-tract infections and treatments for past and present partners.

F.Review social habits for male and female:

1.Smoking: How much, how often, how long.

2.Drugs: How much, how often, how long for each drug.

3.Alcohol: How much, how often, how long.

4.Use of saunas or hot tubs.

5.Exercise, including cycling.

G.Take a complete medication history, specifically review for:

1.Antihypertensives.

2.Antidepressants.

3.Antipsychotics.

4.Muscle relaxants.

5.Testosterone or anabolic steroid use for the male partner.

H.Review for exposure to toxic chemicals, radiation, or known teratogens:

1.Military/war exposure.

2.Employment exposure.

3.Pesticides, nail salons.

I.Inquire about diethylstilbestrol (DES) exposure in utero (for either partner).

J.Review for symptoms of thyroid dysfunction:

1.Weight gain or loss.

2.Change of bowel habits.

3.Intolerance to heat or cold.

4.Appetite changes.

K.Review for systemic diseases:

1.Cardiac.

2.Thyroid disease.

3.Diabetes.

4.Androgen excess in the female.

L.Assess the psychosocial context of the infertility, including personal, emotional, and economic factors; family pressures for children; expectations; timing of pregnancy; consideration of adoption; and stress from failure to conceive.

Other Signs and Symptoms

A.See Pathogenesis section and information in Subjective Data section regarding past medical history.

B.History of not being able to get pregnant over the past 6 to 12 months.

Physical Examination: Male

A.Obtain height, weight, and body mass index (BMI). Check temperature, pulse, respirations, and blood pressure (BP).

B.Inspect:

1.Note general signs and appearance of underandrogenization: decreased body hair, gynecomastia, and eunuchoid proportions.

2.Examine the penis, making note of the location of the urethral meatus; observe urethra for discharge.

C.Percuss: Check deep tendon reflexes (DTRs) for signs of hypothyroidism.

D.Palpate:

1.Neck: Examine thyroid.

2.Genitals: Palpate and measure the testes, the presence and consistency of both vasa and epididymides, and the presence of a varicocele.

E.Rectal examination: Check prostate and seminal vesicles for tenderness and other signs of infection.

Valsalva’s maneuver, performed while the patient stands, helps to reveal small varicocele. Varicocele feels like a bag of worms with bluish discoloration visible through the scrotum. Approximately 23% to 30% of infertile males have varicocele (usually present on the left side). No treatment is necessary if the semen analysis is normal.

Physical Examination: Female

A.Check temperature, pulse, respirations, and BP. Obtain height, weight, and BMI.

B.Inspect:

1.Examine breasts for presence of nipple discharge.

2.Note general signs, and of androgen excess.

Polycystic ovarian syndrome (PCOS) triad includes acne, obesity, and hirsutism.

C.Auscultate abdomen for bowel sounds in all quadrants. Auscultation of the abdomen should precede any palpation or percussion due to the changes in intensity and frequency of sounds after manipulation.

D.Palpate:

1.Neck: Examine the thyroid.

2.Abdomen: Check for tenderness and masses.

3.Back: Check costovertebral angle (CVA) tenderness.

F.Pelvic examination:

1.Perform detailed external peritoneal exam for signs of infection; lesions; or anomalies of clitoris, labia, Skene’s gland, Bartholin’s gland, vulva, and perineum.

2.Speculum examination:

a.Observe length of vagina, position and characteristic of cervix, and any anomalies.

b.Observe the characteristics of cervical mucus: Thin and watery or thick and cloudy; odor; evidence of infection.

3.Bimanual examination: Check uterine size, consistency, contour, mobility, cervical motion tenderness (CMT), and adnexal masses.

A fixed, immobile uterus determined on bimanual exam could indicate the presence of pelvic adhesions from surgery or past pelvic infection.

4.Rectovaginal examination: Palpate uterosacral ligaments for pain and nodularity; evaluate masses and polyps of rectum.

Diagnostic Tests

A.Male factor: Semen analysis—when the semen analysis is abnormal, a thorough evaluation by a urologist or other specialist in male reproduction is indicated.

B.Ovarian factor:

1.Basal body temperature (BBT) is no longer preferred method.

2.Serum progesterone greater than 3 ng/mL indicates recent ovulation. Levels of 10 ng/mL are used for the quality of luteal function.

3.Urinary luteinizing hormone (LH; OPK) for surge.

4.Cycle day 3 follicle-stimulating hormone (FSH)/Estradiol: High values (>10–20) have been associated with poor ovarian stimulation.

5.Clomiphene citrate challenge test (CCCT): Contemporary use has declined.

6.Thyroid-stimulating hormone (TSH) 0.4 to 2.5 are important prepregnancy for fetal brain development.

7.Serum prolactin.

8.Transvaginal ultrasound for antral follicle count: Low antral follicle count (3–6) is associated with poor ovarian response.

9.Antimüllerian hormone (AMH) is preferred biomarker testing for ovarian reserve. Low serum AMH levels (>1 ng/mL) have been associated with poor ovarian stimulation and poor embryo quality.

When nipple discharge is present, check serum prolactin and TSH to rule out hyperprolactinemia and hypothyroidism.

C.Cervical factor:

1.Postcoital test (PCT), at LH surge.

May consider to evaluate the presence of sperm in the cervical mucus in couples when a semen analysis is not available. This is no longer recommended in routine evaluation due to its subjective nature and poor predictability of conception.

2.Assess for spinnbarkeit, during midcycle.

Spinnbarkeit demonstrates that estrogenic mucus is thin, clear, and copious in amount and can stretch to introitus from the cervical os.

Just prior to ovulation, the mucus is the thinnest; mucus threads of 6 to 10 cm from the endocervix are normal.

D.Pelvic or uterine factor:

1.Endometrial biopsy is no longer recommended for evaluating luteal function.

2.Hysterosalpingogram (HSG) evaluates uterine pathology and tubal patency.

3.Sonohystogram—defines the shape and size of the uterine cavity and identifies intrauterine pathology.

4.Ultrasonography.

5.Hysteroscopy—is the definitive method for evaluating intrauterine pathology.

6.Laparoscopy.

E.Other tests:

1.Pap smear with maturation index.

2.Cultures for gonorrhea (GC) and Chlamydia trachomatis (CT).

3.Pregnancy test, if amenorrhea is present.

4.Complete blood count (CBC), sedimentation rate.

5.Mycoplasma culture.

6.Wet mount.

Differential Diagnoses

A.Infertility.

B.Sexual dysfunction.

C.Hypothyroidism.

D.Hypothalamic dysfunction: amenorrhea.

E.Hyperprolactinemia.

F.Menopause.

G.Ovarian failure.

H.PCOS.

I.Asherman’s syndrome.

J.Tubal occlusion.

K.Antisperm antibodies.

L.Endometriosis.

M.Oligo-ovulation.

N.Uterine anomalies: dibroids, synechiae, and septa.

O.Pelvic adhesions.

Plan

A.General interventions:

1.Semen analysis is one of the first steps in an infertility workup. The male should have abstinence of 2 to 5 days prior to analysis. If the first evaluation is abnormal, it should be repeated in 3 months. If still abnormal, consider referral. Normal semen analysis includes the following:

a.Total sperm count: greater than 39 million per ejaculate.

b.Ejaculate volume: 1.5 mL.

c.Percentage motility: 40%.

d.Progressive motility: 32%.

e.Normal morphology: 4%.

2.The male physical examination may be deferred if the semen analysis is normal.

3.The male should always be evaluated early on in the process due to the ease and low cost of an analysis.

4.Female evaluation:

a.The first step is to document ovulation. This may be done through a thorough menstrual history. In ovulatory women, menstrual cycles are regular and predictable, occurring in intervals of 21 to 35 days and accompanied by a consistent pattern of flow characteristics and moliminal symptoms.

b.Serial BBT measurements provide a simple and inexpensive method for evaluating ovulatory function. This is no longer considered the best method in evaluating ovulatory function. Some patients’ temperatures dip just before the day of ovulation and then rise. Ovulation and the development of the corpus luteum manifest as an increase of BBT by 0.6 to 1 degree above the patient’s baseline temperature. The period of highest fertility spans the 7 days prior to the mid-cycle rise. The BBT cannot reliably define the time of ovulation and can be tedious for patients.

c.Urinary LH kits (ovulation predictor kits) can identify the mid-cycle LH surge that precedes ovulations by 1 to 2 days. Patients should begin testing around 5 days prior to ovulation. In a 28-day cycle, this would correlate to cycle day 10. The test is most reliable if performed midday or in the evening, and predicts the days of greatest fertility: the day of the LH surge and the following day.

d.Endometrial biopsy, or sampling of the uterine lining late in the luteal phase: Histology can determine endometrial development, which implies ovulation. However, this test cannot distinguish between fertile and infertile women. It is no longer recommended in the evaluation of ovulatory function.

e.Serum progesterone: When drawn at the appropriate time of the cycle, it is a reliable indication of ovulation. This should be obtained 1 week prior to expected menses. A progesterone level greater than 3 ng/mL provides evidence of recent ovulation. Higher thresholds at mid luteal phase have been used as a measure of quality of luteal function. These levels are ideally greater than 10 ng/mL.

f.Transvaginal ultrasound: A transvaginal pelvic ultrasound can evaluate the number and size of the developing follicles. This provides evidence of follicular growth, collapse of preovulatory follicle, corpus luteal cysts, and luteinization of the endometrial lining. Because of the cost associated with ultrasounds, this should be reserved for patients who are not able to use simpler testing.

g.Evaluation of uterus and fallopian tubes: HSG, performed in radiology, evaluates tubal patency and rules out uterine anomalies. The HSG should be scheduled for the interval between cessation of menstrual flow and ovulation to avoid retrograde flow of menstrual tissue into the tubes and the abdominal cavity.

h.Laparoscopy/hysteroscopy: Diagnostic if used as the final screening examination for infertility. Performed by a gynecologist, it is usually done in the first 2 weeks of the menstrual cycle to ensure that the patient is not pregnant. Direct visualization of the pelvic organs provides data about the degree of adhesion formation, presence of endometriosis or fibroids, and the possibility of surgical repair of damaged tubes. Hysteroscopy may be used to visualize intrauterine pathology including septums, polyps, or fibroids.

B.Patient teaching:

1.Infertile couples often require extensive counseling, including grief counseling, for failure to achieve pregnancy.

2.When couples do not meet the definition of infertility, efforts should be made to maximize fertility:

a.The fertile window spans the 6-day interval ending on the day of ovulation. Intercourse is most likely to result in pregnancy when it occurs within the 3-day interval ending on the day of ovulation. Couples having intercourse every other day mid cycle will maximize their fecundability.

b.Being overweight or underweight, consuming alcohol and caffeine, smoking, and exposure to toxins are all lifestyle factors that affect fertility.

c.Time to conception increases with age. Efforts should be made for women to achieve pregnancy before their mid-30s.

C.Pharmaceutical therapy:

1.Treatment depends on causative factor(s). These may include oral agents, injectable gonadotropins, or in vitro fertilization.

2.Prescription medications must be supervised by physician and/or specialist due to possible complications such as ovarian hyperstimulation.

Follow-Up

A.Follow-up depends on causative factor(s).

Consultation/Referral

A.Consultation and referral should be considered when pregnancy is not achieved within a reasonable time frame and for specialized testing, surgery, and assisted reproductive therapy.