8th Edition APGO Objectives
for Medical Students
Infertility
Rationale
The evaluation and management of an
infertile couple requires an understanding
of the processes of conception and
embryogenesis, as well as sensitivity to
the emotional stress that can result from
the inability to conceive.
Objectives
The student will be able to cite:
 Definition of primary and secondary
infertility
 Causes of male and female infertility
 Evaluation and management
 Psychosocial issues associated with
infertility
Definition

Primary
 Couple
has never conceived
 No conception during first year without
contraception

Secondary - couple has had at least one
prior conception
Scope of problem



Common problem - 1 of every 12 couples or 24
million women
1990 estimated health care costs in U.S. for
infertility were $1.3 billion
Conception rate - fecundability




After 1 mo. ~ 20% will conceive
After 3 mo. 50% will conceive
After 6 mo. 75% will conceive
After 12 mo. 90% will conceive
Etiology of infertility
20-40% of couples will have multiple causes
Female - about 60%
 Tubal
- 35%
 Ovulatory - 15%
 Cervical - 5%
 Other - 5%
Etiology of infertility
20-40% of couples will have multiple causes
Male - 35-40%
 Azoospermia
 Compromised
spermatogenesis
Etiology of infertility
20-40% of couples will have multiple causes
Couple
 Age
(rates vary with female age)
 Sexual life, i.e. frequency
 Cigarette smoking - delays time to
conception
Evaluation
History and physical
Evaluation
Male Factor - semen analysis
Volume - 2-5cc
 pH: 7.5-7.8
 Total count - 40 x 106 - 200 x 106

 Azoospermia = no sperm
 <40 x 106 - Oligospermia
Concentration >20 x 106 /mL count/cc
 >50% motile
 Fructose positive

Evaluation
Male Factor - semen analysis



Normal morphology (>60%)
Liquefaction - 1-20 min.
Possible etiologies







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Genetic disorders, i.e. Klinefelter Syndrome
Endocrinopathies
Varicoceles
Obstruction
Infection
Hypogonadism
Idiopathic
Defect in spermatogenesis
Evaluation
Female Factors

Document ovulation





Basal body temperature chart (sustained rise >10
days)
Day 21 serum progesterone (>5ng/mL)
FSH on Day 3 of cycle - if >15 mIU/mL, abnormal
and fertilization of eggs unlikely - ovarian failure,
diminished ovarian reserve
Exclude cervical factors - post-coital test (SimsHuhner Test) - look for five or more actively
motile sperm in cervical mucus
Tubal factors


Hysterosalpingogram to look for tubal patency
Laparoscopy to look for peritoneal factors
Therapy
Male factor
 Urology consult
 Donor sperm insemination
 Intrauterine insemination (IUI)
 In Vitro Fertilization- Embryo Transfer
(IVF-ET)
 IVF with ICSI (intracytoplasmic sperm
injection)
Therapy
Female factors
 Poor or lack of cervical mucus Consider
IUI Low-dose estrogen
 Tubal occlusion - corrective surgery
and/or IVF
 Anovulation - ovulation inducers
Therapy
Ovulation Inducers
Rate of Ovulation Pregnancy
Clomiphene
80%
40%
HMG
90%
70-80%
Bromocriptine
90%
70-80%
GnRH
80%
50-80%
Ovarian drilling
70-80%
45-60%
Therapy
Assisted reproductive technology
 Requires




Controlled ovarian hyperstimulation
Retrieval of oocytes
In vitro fertilization and embryo transfer
Procedures



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IVF-ET (In Vitro fertilization-embryo transfer)
GIFT (Gamete intrafallopian transfer)
ZIFT (Zygote intrafallopian transfer)
ICSI (Intracytoplasmic sperm injection)
Psychological issues
Conflicting feelings about parenthood;
active participation of both partners
throughout
References
Speroff L, Glass RH, Kase NG. Clinical
Gynecologic Endocrinology and Infertility,
5th ed., Baltimore, MD, 1994, Williams &
Wilkins.
Adapted from Association of Professors of
Gynecology and Obstetrics Medical
Student Educational Objectives, 7th
edition, copyright 1997
Clinical Case
Infertility
Patient Presentation
A 37-year-old female and her 37-year-old
husband present with the complaint of a
possible fertility problem. The couple has been
married for 2 years. The patient has a 4-yearold daughter from a previous relationship. The
patient used birth control pills until one-and-ahalf-years-ago. The couple has been trying to
conceive since then and report a high degree of
stress related to their lack of success.
Patient Presentation
The patient reports good health and no problems in
conceiving her previous pregnancy or in the vaginal
delivery of her daughter. She reports that her
periods were regular on the birth control pill, but
have been irregular since she discontinued taking
them. She reports having periods every 5-7 weeks.
Past history is remarkable only for mild depression.
Imipramine 150 mg qhs for the last 8 months is her
only medication. She works as a cashier, runs 1224 miles each week for the last 2 years, and has no
history of STDs, abnormal Paps, smoking, alcohol
or other drugs. She has had no surgery.
Patient Presentation
The patient’s partner also reports good health and reports
no problems with erection, ejaculation or pain with
intercourse. He has had no prior urogenital infections or
exposure to STDs. He has had unprotected sex prior to
his current relationship, but has not knowingly
conceived. He has no medical problems or past
surgery. He works as a long-distance truck driver and is
on the road 2-3 weeks each month. He smokes a pack
of cigarettes a day since age 18 and drinks 2-3 cans of
beer 3-4 times a week when he’s not driving. He
occasionally uses amphetamines to stay awake while
driving at night. The couple has vaginal intercourse 3-5
times per week when he is at home.
Patient Presentation
Physical exam
The patient is 5’9” and weighs 130 pounds.
Breast exam reveals no tenderness or masses,
but bilateral galactorrhea on compression of the
areola. Pelvic exam reveals normal genitalia, a
well-estrogenized vaginal vault mucosa and
cervical mucus consistent with the proliferative
phase. The uterus is anteflexed and normal in
size without masses or tenderness.
Patient Presentation
Laboratory
TSH
Free T4
Prolactin
FSH
LH
Results
Normal Values
2.1 mIU/ml
1.1 ng/dl
60 ng/ml
6 mIU/ml
4 mIU/ml
0.5-4.0 mIU/ml
0.8-1.8 ng/dl
<20 ng/ml
5-25 mIU/ml
5-25 mIU/ml
Basal body temperature chart shows a
monophasic temperature graph.
Patient Presentation
Partner
Semen analysis revealed 2 cc of semen,
4 million per mL, 30% normal forms and
20% motility.
Management
The patient’s major infertility factor is anovulation;
the most likely cause is hyperprolactinemia from
imipramine. The prolactin level is elevated,
consistent with drug-induced
hyperprolactinemia. The patient was instructed,
in conjunction with her therapist, to taper off the
imipramine. Her follow-up basal body
temperature chart was biphasic, consistent with
ovulatory cycles.
Management
The patient’s partner, however, has a
semen analysis that is consistent with
oligospermia. The couple was given their
options of: 1) In Vitro fertilization with
ISCI; 2) artificial insemination with
partner’s sperm; 3) artificial insemination
with donor sperm; or 4) adoption.
Teaching pointes
1. Multiple causes must be considered for
infertility diagnosis and treatment.
Female and male reproductive anatomy
and physiology should be reviewed in
order to encompass the large differential
diagnosis and the different factors that
may contribute to infertility or subfertility.
Teaching pointes
2. Infertility is defined as one year of unprotected
coitus without conception. Infertility may be
primary: a woman who has never achieved
pregnancy, or secondary: a woman who has
achieved pregnancy in the past. Causes of
infertility include tubal and pelvic pathology
(35%), male problems (35%), ovulatory
dysfunctional (15%), unexplained infertility
(10%) and unusual problems (10%).
Teaching pointes
3. Components of an initial infertility
workup include a thorough history and
physical examination. Laboratory
investigations include a semen analysis
to assess male causes of infertility, a
method to document that ovulatory
cycles are occurring and, often, a
hysterosalpingogram to rule out tubal
disease.
Teaching pointes
4. Disorders of ovulation include polycystic
ovarian syndrome (PCOS),
hyperprolactinoma, thyroid dysfunction and
hypothalamic causes and may be diagnosed
by history, as well as laboratory tests that
document the occurrence of ovulatory cycles.
Basal body temperature recording, urinary LH
testing, endometrial biopsy and luteal phase
serum progesterone testing are all tests that
may help confirm the presence or absence of
ovulation.
Teaching pointes
5. Dysfunction of the hypothalamic-pituitaryovarian axis and medical illness, including
thyroid disease and pituitary tumors, can
cause ovulatory disturbances. Further
laboratory workup targeting these problems
should be performed when history,
examination, and initial laboratory evaluation
indicate ovulatory dysfunction. Medication
can also cause ovulatory problems.
Teaching pointes
6. Ovulatory dysfunction may sometimes be
treated with correction of medical disease or
change of medications. Most often, ovulatory
dysfunction is treated empirically with
ovulation induction agents such as
clomiphene citrate. A thorough understanding
of the normal physiology and pathophysiology
of the menstrual cycle aids greatly in the
understanding of ovulatory dysfunction.
Teaching pointes
7. Management of tubal disease is often
surgical, including lysis of adhesions and
removal of tubal obstruction via either
laparoscopy or laparotomy, depending on the
severity of the disease.
8. Male fertility problems include varicocele, duct
obstruction, sperm antibodies, hypogonadism,
testicular hyperthermia, drug use and
industrial pollutants.