Infertility: the role of the family doctor

Infertility: the role of the family doctor
By: Carroll Haymon, M.D.

Definitions 
    * Infertility = Inability of a couple practicing frequent intercourse and not using contraception to fail to conceive a child within one year.
    * Infertility affects 15-20% of couples, or 11 million reproductive age people in the U.S.

Causes of infertility 
    * Tubal pathology  35%
    * Male factor   35%
    * Ovulatory dysfunction 15%
    * Unexplained   10%
    * Cervical/other   5%

Counsel patience!
    * In normal young couples:
          o 25% conceive after one month
          o 70% conceive after six months
          o 90% conceive by one year
    * Only an additional 5% will conceive in an additional 6-12 months

Fecundity and Age
    * In a federal survey:
          o Impaired fertility in women < 25y is 11.7%
          o Impaired fertility in women > 35y is 42.1%
    * In another study:
          o 74% of women < 31y conceived in one year.
          o 54% of women >35y conceived in one year.
    * Our challenge: presenting data in a supportive, non-judgmental manner

Tubal/ Pelvic pathology
    * Congenital anomalies
    * Tubal occlusion
    * Evaluated by:
          o hysterosalpingogram
          o laparoscopy
          o hysteroscopy
    * May occur as sequelae of
          o PID
          o endometriosis
          o abdominal/pelvic surgery
          o peritonitis

Male factor
    * Male partner should be evaluated simultaneously with female
    * Causes of male infertility:
          o reversible conditions (varicocele, obstructive azoospermia)
          o not reversible, but viable sperm available (ejaculatorydysfunction, inoperative obstructive azoospermia)
          o not reversible, no viable sperm (hypogonadism)
          o genetic abnormalities
          o testicular or pituitary cancer

Ovulatory dysfunction
    * Causes 15% of infertility
    * Diagnosed by menstrual irregularities, basal body temperature charting, ovulation prediction kits, serum progesterone levels.
    * Causes of ovulatory dysfunction:
          o polycystic ovary syndrome
          o hypothalamic anovulation
          o hyperprolactinemia
          o premature and age-related ovarian failure
          o luteal phase defect (theoretical)

Polycystic Ovarian Syndrome
    * Oligomenorrhea/amenorrhea and hyperandrogenism
    * Prevalence: 5%. Among women with O.D., 70% have PCOS.
    * Clinical evidence: hirsutism, acne, obesity
    * Lab evidence: elevated testosterone, elevated DHEA-S.
    * “Polycystic ovaries” supportive, not  diagnostic

PCOS: Treatment Approach 
    * Weight loss if BMI>30
    * Clomiphene to induce ovulation
    * If DHEA-S >2, clomiphene + glucocorticoid (dexamethasone)
    * If clomiphene alone unsuccessful, try metformin + clomiphene.

Hypothalamic Anovulation
    * Low levels of GnRH, low of normal levels of FSH/ LH, low levels of endogenous estrogen.
    * Associated factors: low BMI (< 20), high-intensity exercise, extreme diets, stress.
    * Treatment: lifestyle modification.

Hyperprolactinemia 
    * Causes: pituitary adenoma, psych meds.
    * Test for: pregnancy, thyroid disease.
    * Imaging: MRI for macro vs microadenoma
    * Treament: Bromocriptine (dopamine agonist). After correction, 80% of women will ovulate, 80% will get pregnant.
    * Discontinue treatment once pregnancy established.

What Can I Do?
Infertility Evaluation for the Family Doctor
History and Physical - Female

    * History
          o menarche, puberty
          o menstrual hx
          o preganancies, abortions, birth control
          o dysparenunia, dysmenorrhea
          o STD’s, abdominal surg, galactorrhea
          o Weight loss/gain
          o Stress, exercise, drugs, alcohol, psychological
    * Physical
          o weight/BMI
          o thyroid
          o skin (striae? Acanthosis nigracans?)
          o pelvic (vaginal mucosa, masses, pain)
          o rectal (uterosacral nodularity)

History and Physical - Male
    * History
          o prior fertility
          o medications
          o h/o diabetes, mumps, undescended testes
          o genital surgery, trauma, infections
          o ED
          o drug/alcohol use, stress
          o underwear, hot tubs, frequent coitus
    * Physical
          o habitus, gynecomastia
          o sexual development
          o testicular volume (5x3 cm)
          o epididymis, vas, prostate by palpation
          o check for varicocele

Trouble in Paradise
    * Don’t wait a year if:
          o irregular menses; intermenstrual bleeding
          o h/o PID
          o h/o appy with rupture
          o h/o abdominal surgery
          o dyspareunia
          o age > 35
          o male factors

On your first visit:
    * Semen analysis
    * Confirm ovulation
          o basal body temperature charting
          o ovulation predictor kits (detect LH surge)
          o consider serum progesterone on day 21
    * Labs:
          o TSH and prolactin. DHEA-S if concern for PCOS.
          o FSH & estradiol on cycle day 3 if >35y.
          o Cervical cultures prn.

Three months later 
    * Hysterosalpingogram
          o evaluates tubal patency and uterine cavity shape
          o noninvasive but involves a tenaculum
          o performed by radiology with gynecology supervision
          o diagnostic and therapeutic
    * Postcoital test
    * endometrial biopsy
    * immune testing for antisperm antibodies
    * routine cervical cultures

Clomiphene citrate 
    * Effective for anovulatory patients.
          o Also used in unexplained fertility, but no data to support.
          o Most effective for women with nomal FSH and estrogen, least effective in hypothalamic amenorrhea or elevated FSH.
    * Induces ovulation by unknown mechanism
    * Most pregnancies occur in first 3 cycles. 80% will ovulate, 40% will become pregnant in 3 cycles.

Clomiphene - complications 
    * 7% twin gestations, 0.3% triplet gestations
    * Miscarriage rate = 15%
    * Birth defect rate unchanged from controls
    * Side effects: hot flashes, adnexal tenderness, nausea, headache, blurry vision
    * Contraindications: pregnancy, ovarian cysts.

Clomiphene - Administration
    * 50 mg po qd, cycle day 3 through 7. Induce bleeding first with progesterone if amenorrheic.
    * Intercourse QOD cycle days 12 - 17.
    * Track ovulation with BBT or ovulation detection kits.
    * Increase dose to 100 qd, then 150, if no ovulation occurs.

Bibliography 

Case 1 

    * A 24 year old couple comes to see you. They have been trying to get pregnant for 8 months.
          o What questions do you ask?
    * The woman tells you she has never been pregnant. She has a regular 28 day cycle and bleeds for 4 days each month. Her medical history is unremarkable except she “got really sick” when she was 16 and had “nasty stuff coming from down there”
          o what do you do next?

Case 2
    * A 35 year old woman and her 31 year old male partner come to see you. They have been trying to get pregnant for 6 months.
          o What do you ask?
    * She says her periods have been irregular since she went off the pill a year ago. She has never been pregnant.  He has fathered a child by another woman several years ago.
          o What do you look for on exam?
          o What lab tests do you order today?
          o Do you give them homework?
    * They come back 3 months later with BBT charts showing no discernable pattern.  Lab tests, including semen analysis, were all normal.
          o What is the diagnosis?
          o What do you do next?
    * You begin discussion of clomiphene.  They want to know the side effects, and if this means they’ll have sextuplets and get a free house like the folks on TV.
          o What do you tell them?
          o How do you administer the clomiphene?

    * They come back in one month.  She feels “like a total bitch - excuse me, doctor” on the clomiphene.  She is not pregnant.  BBT charting shows a mid-cycle temperature rise.
          o What happens next?

Infertility: the role of the family doctor