INFERTILITY

J O N E L L E B A L O L O Y, M D
DEFINITION OF TERMS
• INFERTILITY- reduced capacity to conceive
– Married couple
– Inability to conceive after 1 year of trying, if >35 y/o- 6 months of
trying
– 7.4% of all women 15-44 y/o has infertility
– Increases with increasing age of female partner
• SUBFERTILITY- decreased capacity for pregnancy
• FECUNDABILITY- monthly ability to get pregnant (20%)
• IMPAIRED FECUNDITY- all women who have difficulty conceiving or
carrying a pregnancy to term
– 10.9% reproductive age group
• Increasing infertility rate with correlation to age due to diminished
ovarian reserve: 17% of cycles
 FECUNDABILITY

• After 2 years of trying to conceive 4%

will not have conceived. Fecundabiity is
0.08. 57% will conceive next year
• If 2% still not pregnant after 3 years
fecundability drops 0.06, 0.05 and 0.04 in
the next 3 years. In 4th, 5th and 6th yrs
only 48%, 42% and 37% conceive
without treatment
• Spontaneous conception among infertile
couples with unexplained fertility without
treatment
• 38.2% conception rate at 3 years and 45%
after 7 years
CAUSES OF INFERTILITY
• Ovulatory disorders- 27%
• Male factors- 25%
• Tubal disorders- 22% NOT SHOWN TO CAUSE
• Endometriosis- 5% INFERTILITY
• Other factors- 4% • Antisperm antibodies
• Unexplained factors- 17% • Luteal phase deficiency
• Subclinical genital infection
• Subclinical endocrine abnormalities
(hypothyroidism and
hypoprolactenimia)
EVALUATION OF INFERTILE FEMALE
• After 1 year of unprotected coitus
• Female partner > or = 35 y/o
• History of oligomenorrhea/amenorrhea
• History of pelvic inflammatory disease/ stage III-IV endometriosis
• Male partner known to be subfertile

Optimal Evaluation of Infertile Female

Practice committee of American Society for Reproductive Medicine (2004)
HISTORY
• Gravidity, parity, pregnancy outcome and associated complications
• MIDAS
• Contraception and coital frequency
• Duration of infertility and results of any previous evaluation and treatment
• Past surgery and its indications and outcome
• Pelvic inflammatory disease or exposure to STDs or unusual childhood disorders
• History of abnormal pap smears and subsequent treatment
• Current medications and allergies
• Occupation and use of tobacco, alcohol and other drugs
• Family history of birth defects, mental retardation or reproductive failure
• Symptoms of thyroid disease, galactorrhea, hirsutism and dyspareunia
Optimal Evaluation of Infertile Female
Practice committee of American Society for Reproductive Medicine (2004)
PHYSICAL EXAMINATION
• Weight and BMI
• Identify any:
– Thyroid enlargement, nodule or tenderness
– Breast secretions
– Signs of androgen excess
– Pelvic or abdominal tenderness
– Vaginal or cervical abnormality, secretions or discharge
– Uterine size, shape, position and mobility
– Adnexal mass or tenderness
– Cul-de-sac mass, tenderness or nodularity
Optimal Evaluation of Infertile Female
Practice committee of American Society for Reproductive Medicine (2004)
DIAGNOSTIC EVALUATION
• Documentation of ovulation
• Semen analysis
• Evaluation and laboratory tests
• Ultrasound
• Blood testing
• Hysterosalpingography
• Postcoital test
• Laparoscopy
 DOCUMENTATION OF OVULATION
• MENSTRUAL HISTORY
– Oligomenorrhea (menses at intervals of 35 days or longer)
• treated with agents that induce ovulation
• Direct or indirect measurement of progesterone is unnecessary
until after therapy is initiated

• BASAL BODY TEMPERATURE

– Indirect evidence that ovulation has taken place. NOT a
precise information about ovulation timing
– Taken after awakening after at least 6h of sleep and prior to
ambulating with sublingual thermometer
– Short interval of luteal phase temperature elevation (<11
days)- absent or poor quality ovulatory function
DOCUMENTATION OF OVULATION
• SERUM PROGESTERONE
– To evaluate ovulatory function
– 3-5ng/mL- some ovulatoryfunction
– >10ng/mL- 1 day of luteal phase of
normal ovulatory conception
• URINARY LUTEINIZING
HORMONE
– “ovulation predictor kits”
– Reliable but indirect evidence of
ovulatory function
– More accurate in evening urine
• ENDOMETRIAL BIOPSY
– Diagnostic method for adequacy of
ovulation and luteal function
– Not indicated
• PELVIC ULTRASOUND
– Determine fibroids, endometriosis
and other pathologies
– Antral follicle count can be
obtained- similar to AMH in
assessment of ovarian reserve
LABORATORY TESTS
• Other evaluation
– TSH and prolactin
– Cycle day 3 FSH or clomiphene citrate challenge test- to evaluate ovarian
reserve
• >35 y/o
• Single ovary or history of previous ovarian surgery
• Documented poor response to exogenous gonadotropin stimulation
• CBC, blood type, Rh factor, rubella status
• Papsmear within 12 months of previous test
• Screen for genetic carrier status (not mandatory)
• Infectious disease screening (chlamydia and gonorrhea)- for patients
undergoing IVF or insemination
• >35 y/o
– FSH and estradiol should be obtained on cycle day 2 or 3
– Inc. FSH
• >10mIU/mL- decreased ovarian reserve
• >20 mIU/mL- poor prognosis
– Inc. estradiol
• >70pg/mL-decreased prognosis regarding ovarian reserve
• Antimullerian hormone or Mullerian-inhibiting substance
– Not standardized
– Produced by granulosa cells of small growing follicles  highest
in young reproductive women
– 0.05ng/mL- menopause occurs within 4-5 years
– Higher in patients with PCOS
– >2ng/mL- larger cohort of small follicles hence increased ovarian
reserve
– Constant and stable throughout menstrual cycl
– Use of OCP decreases value by 15-20%
• Documentation of ovulation and semen analysis should be
treated before proceeding with more costly and invasive
procedures
• Most anovulatory women (80%) conceive after induction
of ovulation with therapeutic agents,
• If these diagnostic tests are normal 
hysterosalpingoraphy should be perfomed
– During follicular phase
HYSTEROSALPINGOGRAPHY
• Determines patency of tubes
• If disease is present, determine magnitude of disease, provide
information about the lining of oviduct and uterine cavity
• Schedule the week after menses
– Avoid possible pregnancy
– Better definition of uterine cavity- endometrium is thin
• CONTRAINDICATED:
– History of salphingitis
– Tenderness on pelvic exam
• Screen chlamydia or gonorrhea before performing HSG
• Prophylactic antibiotics
– Doxycycline 100mg BID x 3 days- 1 day before procedure
– (+) hydrosalpinx- doxycycline extended for 1 week
• Water-soluble contrast medium
– better visualization of tubal mucosal folds and vaginal markings
Normal HSG Normal ampullary folds

Bilatral salpingitis isthmica nodosa

(proximal disease)
Bilateral hydrosalpinges
Proximal obstruction
- Uterine spasm due to discomfort of procedure
- Obstruction due to tubal debris
- Fluoroscopic/hysteroscopic selective tubal cannulation-
confirm or exclude proximal tube occlusion
LAPAROSCOPY
• Final step in infertility investigation if all tests were normal
• Indications:
– Suspicious ultrasound examination
– Previous pelvic surgery or appendicitis
– Pelvic pain or dyspareunia
POSTCOITAL TEST
• No longer routine
• Specimen of cervical mucus is obtained within hours after
intercourse prior to ovulation examined for presence of
motile sperm (Practice committee of American Society for
Reproductive Medicine (2004)
• At least 5 motile sperm- normal cervical mucus higher
rate of conception
MEDICAL TREATMENT FOR ANOVULATION
CLOMIPHENE CITRATE
- first-line pharmacologic agent for women with oligomenorrhea and
with amenorrhea who have sufficient ovarian estrogen production
- MOA: Estrogen antagonist
- Bind to estrogen-binding sites in hypothalamus  hypothalamus perceives
hypoestrogen state  Inc. release of gonadotropins by pituitary  Inc. FSH
and LH  Oocyte maturation and increased estrogen production
- Dose- given daily for 5 days beginning 3-5 days after onset of
spontaneous menses or withdrawal bleeding induced with
progesterone
MEDICAL TREATMENT FOR ANOVULATION

AROMATASE INIHIBITORS (LETROZOLE)

- MOA: Estrogen antagonist
- Bind to estrogen-binding sites in hypothalamus  hypothalamus perceives
hypoestrogen state  Inc. release of gonadotropins by pituitary  Inc. FSH and
LH  Oocyte maturation and increased estrogen production
- Inc. intraovarian androgen levels  increased FSH sensitivity
- 2.5 or 5mg OD for 5 days beginning on cycle days 3-5
MEDICAL TREATMENT FOR ANOVULATION
METFORMIN
- Biguanide used to control blood sugar in diabetics
- Adjunct therapy for induction for PCOS
- MOA: inhibits ovarian androgen steroigenesis and acts on
endometrium
- Dose: 1500mg/day (long-acting tablets)
MEDICAL TREATMENT FOR ANOVULATION

GONADOTROPIN
• For ovulation induction when estrogen levels are low
(<30pg/mL), no response to clomiphene or letrozole, lack
of withdrawal bleeding after progestogen administration–
unresponsive to ral therapies
OVARIAN HYPERSTIMULATION SYNDROME
- 0.5% of women receiving gonadotropins
- Massive fluid shifts  ascites, pleural effusion, electrolyte
disturbance, thromboembolism
- HCG triggers the syndrome  pregnancy makes it worse,
symptoms abate 1 week after absense of pregnancy
- Treatment:
- Supportive
- Correction of electrolyte imbalance and maintenance of UO-
greatest importance
UTERINE CAUSES OF INFERTILITY
• INTRAUTERINE ADHESIONS- recurrent abortion,
– Treatment: hysteroscopic lysis of adhesions

• LEIOMYOMA- many women with leiomyoma have no difficulty

conceiving
– Decreased pregnancy rate with submucous fibroids, larger
intramural fibroids (>4cm)  distort uterine cavity
– Treatment: Myomectomy
• TUBERCULOSIS- endometrial biopsy
and culture to confirm
– Radiographic features of pelvic tb
• Calcified lymph nodes or granulomas in the
pelvis
• Tubal obstruction in distal isthmus or
proximal ampulla– PIPE STEM
CONFIGURATION of tube proximal to the
obstruction
• Multiple strictures
• Irregular contour of ampulla
• Deformed or obliteration of endometrial
cavity without previous curettage
– Treatment: TB medication. Considered
 ENDOMETRIOSIS

• 40% of infertile women

• Reduced fecundity in relation to extensiveness of the
disease. Women with extensive disease have mechanical or
obstructive cause of infertility as well
• Treatment: surgery if patient with pain and large
endometrioma are present
UNEXPLAINED INFERTILITY

• Couples with normal ovulation and pelvic evaluation with

normal uterus, patent tubes on hysterosalpingogram as well
as normal semen analysis

• Treatment: ovarian stimulation with CC or gonadotropins +

IUI
• continued intercourse for 6 mos prior to treatment
SEMEN ANALYSIS
• 20% of couples with infertility – Viscosity
• Abstain from ejaculation for – Sperm density
2-3 days before collection of – Sperm morphology
semen sample • Fertilizing ability

• Semen profile reflects sperm – Sperm motility

production occurred 3 months • Repeat test if an abnormality
ago is found  (+) abnormality
refer to urologist

• Parameters to evaluate semen:

MALE INFERTILITY