Gynecology: Infertility

Guest · **posting in usmle forum about Obstetrics & Gynecology**

I. General. Involuntary infertility is defined as the inability to conceive after one year of unprotected intercourse. Affects 10%-15% of couples. The incidence is increasing because of delayed childbearing and an increased incidence of STDs and PID

A. Average time to conception. 3 months: 25% of normal couples conceive in the first cycle, 85% within one year.
B. Acknowledge the emotional nature of problem and define infertility as a couple’s shared concern. Inquire about partner responses.

II. Common major problems. Anovulation (15%), male factors (35%), tubal and pelvic disease (35%), or a combination of these factors. Less common problems include cervical problems or immune infertility. Smoking decreases female fertility.

III. Diagnostic Evaluation and Treatment
A. Thorough history and physical examination of both male and female. Ask about menstrual history, obstetric history, previous children fathered, prior contraceptives used, history of STDs or PID, pelvic surgery, cervical treatments, medications or herbs used. Determine coital frequency, sexual practices, impotence, dyspareunia, use of postcoital douches, lubricants (even UK or petroleum jelly can be spermicidal: recommend vegetable oil).

B. Preconception evaluation to address risk factors before conception (e.g., folate).

C. Semen analysis. Since 35% of couples have some component of male factor infertility, a semen analysis should be one of the initial tests done. Collected after a 2 or 3-day period of abstinence in glass container. Male causes for infertility include testicular disorders, varicocele, hypospadias, ductal obstruction, endocrine abnormalities, retrograde ejaculation, and genetic disorders (Klinefelter’s syndrome).

1. Normal semen analysis. (WHO criteria). Volume >2 ml, sperm count >20 million/ml, motility >50% with forward progression, morphology >30% normal forms, WBC <1 million/ml.

2. If normal, look for female factors causing infertility.

3. If pyospermia present (>1 million WBC/ml), search for and treat infections of urethra, epididymis, or prostate.

4. If otherwise abnormal, repeat in 2 months. If abnormalities persist, refer to urologist for further evaluation.

D. Ovulation assessment.

1. Symptoms of ovulation (such as Mittelschmerz, PMS), length and regularity of menstrual cycle.

2. Basal body temperature charting. Should see a 0.4-0.6° F rise the day after ovulation that is sustained 11-16 days until menstruation. To maximize the chances of conception, advise coitus every 36-48 hours from 4 days before ovulation until 2 days after (some patients find this schedule difficult psychologically)

3. Evaluate and treat menstrual abnormalities.

a. Amenorrhea. Rule out premature ovarian failure, confirmed by FSH >40 mg/ml and estradiol <40 picograms/ml in same sample.

b. Oligomenorrhea with hirsutism or galactorrhea. Suspect POCS. Assess for hyperprolactinemia, and, if present, work up to exclude pituitary cause. If idiopathic hyperprolactinemia, treat with bromo-criptine 2.5 mg QHS until BBT demonstrates ovulation. Dose can be increased by 2.5 mg every 3 days until prolactin normal with maximum daily dose 15 mg divided BID. If no ovulation in 2-3 months, add clomiphene. Hypothyroidism can be associated with hyperprolactinemia and should be evaluated and treated.

c. Ovulation induction if documented defect found.
1. Clomiphene citrate 50 mg QD for days 5 to 9 after either induced or spontaneous menses. Monitor for ovulation with BBT or ovulation kits that detect LH surge about 12 to 24 hours before ovulation to allow timing of intercourse. If ovulation fails to happen, in the next cycle the dose can be increased to 100 mg QD, up to 200 mg QD in a stepwise fashion each cycle to achieve ovulation. Side effects include ovarian enlargement (pain, bloating) and hot flashes. 5% to 10% of patients have multiple gestation. Advise coitus for 1 week beginning 5 days after the final dose of clomiphene

2. If ovulation does not occur on maximal doses of clomiphene, or if a short luteal phase is noted, a single dose of HCG 10,000 IU IM can be given 7 days after the final dose of clomiphene. Advise coitus that day and for the following 2 days.

3. Human menopausal gonadotropin (Pergonal) is used for hypothalamic-pituitary insufficiency. Multiple gestations occur at rates higher than those with other ovulation regimens, and close monitoring of follicle production is required. Consultation is recommended.

d. Luteal phase defect is controversial and diagnosis by endometrial biopsy or serum progesterone levels is inexact. Luteal phase defect is suspected when a short interval between ovulation and menses is noted on BBT charting. Clomiphene citrate can be used empirically if no other factors identified.

1. Low serum progesterone level (<10 mg/ml) on day 21 of cycle is suggestive of luteal phase defect.

2. Endometrial biopsy between days 22-24 that is out of phase >2 days relative to ovulation estimated by BBT also suggests luteal phase defect.

3. If these tests are abnormal, treat with supplemental vaginal progesterone suppositories 25 mg BID starting 3 days after ovulation. Continue until menses or if pregnancy occurs, continue until week 10 when placental progesterone is sufficient to support pregnancy.

E. Tubal functioning related to prior PID, ectopic, abdominopelvic surgery, IUD use. Hysterosalpingogram should be done to assess tubal patency and identify uterine anomalies, fibroids, and synechiae. Perform 2-6 days after end of menses to minimize possibility of disrupting a pregnancy.

F. Endometriosis. Diagnosed by laparoscopy if no cause found after work-up as outlined above.

G. Infections of the cervix with Ureaplasma and Mycoplasma have been implicated in infertility. Culture cervical mucus; some authorities presumptively treat both partners with doxycycline 100 mg PO BID x 7 days.

H. Cervical factors, postcoital testing, and the role of sperm antibodies are controversial.

IV. Other Options. Unexplained infertility and male factor infertility can be treated in specialized centers with intrauterine insemination of washed sperm or in vitro fertilization (IVF) which encompasses gamete intrafallopian transfer (GIFT), intracytoplasmic sperm injection (ICSI) and other techniques. Success rates are generally around 50% after up to 6 cycles in women under 35.