Infertility
UNC School of Medicine
Obstetrics and Gynecology Clerkship
Case Based Seminar Series
Objectives for Infertility
 Define infertility
 Describe the causes of male and female infertility
 Describe the evaluation and initial management of an
infertile couple
 List the psychosocial issues associated with infertility
Definition
 Failure of a couple to conceive after 1 year of regular
intercourse without use of contraception
 Primary infertility – No prior pregnancies
 Secondary infertility – Prior pregnancy
Prevalence
 Infertility affects 10-15% of reproductive-age couples in the U.S.
 Approx. 85% of couples achieve pregnancy within 1 year
 Conception rate (fecundability)
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25% conceive within 1 mo.
60% conceive within 6 mo.’s
75% conceive within 9 mo.’s
90% conceive within 18 mo.’s
Etiology
Successful conception requires a specific series of events:
1.
2.
3.
4.
5.
6.
7.
Ovulation of competent oocyte
Production of competent sperm
Juxtaposition of sperm and oocyte in a patent reproductive tract
Fertilization
Generation of a viable embryo
Transport of the embryo to the uterine cavity
Implantation of the embryo into the endometrium
Etiology
 Major causes of of infertility:
 Female factor – 60%
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Ovulatory dysfunction
Abnormalities of female reproductive tract
Peritoneal factors
Reproductive aging
 Male factor – 20%
 Abnormal semen quality
 Abnormalities of male reproductive tract
 Idiopathic – 15%
Infertility in ~ 20-40% of couples has multiple causes
Infertility: History
 Female
 Duration of infertility and prior evaluation or therapy
 Menstrual cycle (length and characteristics)
 Symptoms associated with ovulation (e.g. breast tenderness, bloating, mood
changes)
 Full OBHx and GynHx
 Prior pregnancies, surgeries, or STD’s
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Sexual history (frequency of intercourse)
Chronic medical illness
Family history (infertility, birth defects, genetic disorders)
Social history (smoking, EtOH, drugs)
Infertility: History
 Male
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Prior children
Genital tract infections
Genital surgery or trauma
Chronic medical illness
Medications (e.g. Furantoins, CCB)
EtOH, drugs, or smoking
Sexual history (frequency of intercourse)
Infertility: Physical Exam
 Female
 Height, weight , BMI
 Pelvic exam
 Masses
 Tenderness (Adnexa, Cul-de-sac)
 Structural abnormalities (Vagina, Cervix, or Uterus)
 Male (Urologist referral)
 Evidence of androgen deficiency
 Structural defects (e.g. varicocele, hernia)
Male factor: Evaluation
Male Factor
Initial evaluation
Further evaluation
Semen analysis
Urologic evaluation
FSH, LH, and testosterone level
Genetic evaluation
Epididymal sperm aspiration (PESA, MESA)
Testicular biopsy
Male factor: Evaluation
 Semen analysis
 Following 2-4 day period of abstinence
 Repeated x1 for accuracy
Element
Reference value
Ejaculate volume
1.5-5.0 mL
pH
> 7.2
Sperm concentration
> 20 million/mL
Motility
> 50%
Morphology
> 30% normal forms
Male factor: Evaluation
 Urologic evaluation
 Physical Exam
 Varicocele
 Congenital absence of vas deferens (CAVD)
 Transrectal ultrasound
 Vasography, Seminal vesiculography
 Epididymal sperm aspiration (PESA or MESA)
Male factor: Evaluation
 Endocrine evaluation
 Indication: Oligospermia (< 10million/mL) or sexual dysfunction (decreased
libido, impotence)
 FSH, LH, testosterone
 Genetic evaluation
 Indication: Azoospermia (no sperm)
 CFTR mutation
 Karyotype (Klinefelter’s, Y chromosome deletion)
 Testicular biopsy
 Indication: Nonobstructive azoospermia
 Palpable vasa
 Normal testis volume
 Normal FSH/LH
Female factor: Evaluation
Factor
Initial evaluation
Further evaluation
Ovulation
History and physical exam
Basal body temp charting
Ovulation predictor kit
Mid-luteal phase
progesterone level
Endocrine testing
Endometrial biopsy
Reproductive tract
(uterus or fallopian
tubes)
Hysterosalpingogram (HSG)
Ultrasound
Saline-infusion sonography
Hysteroscopy
Laparoscopy
Peritoneal
Laparoscopy
Reproductive aging
FSH, estradiol, or AMH
Female factor: Menstrual Cycle
Female factor: Evaluation
 Ovulation
 Initial evaluation:
 Basal body temp – rise for > 10 days indicates ovulation
 Ovulation predictor kit – detects LH surge in urine
 Further evaluation:
 Mid-luteal phase progesterone level - level > 3 ng/mL provides
qualitative evidence of recent ovulation
 Endocrine testing (TSH, prolactin, FSH, LH, Estradiol, DHEA-S)
 Endometrial biopsy
 Not routinely performed
Female factor: Evaluation
 Reproductive tract
 Initial evaluation:
 Hysterosalpingogram (HSG)
 Detect uterine anomalies (septate or bicornuate uterus, uterine
adhesions, uterine leiomyoma)
 Detect patency of fallopian tubes (occlusion, hydrosalpinx, salpingitis)
 Ultrasound – alternative to HSG to evaluate uterus
Female factor: Evaluation
 Reproductive tract
 Further evaluation:
 Saline-infusion sonography (SIS)
 Hysteroscopy
 Laparoscopic chromotubation
Female factor: Evaluation
 Peritoneal factors
 Laparoscopy
 Endometriosis
 Pelvic/adnexal adhesions
Female factor: Evaluation
 Reproductive aging
 Indications:
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> 35 years of age
1st degree relative with early menopause
Previous ovarian insult (surgery, chemotherapy, radiation)
Smoking
Poor response to ovarian stimulation
Unexplained infertility
Candidate for IVF
Female factor: Evaluation
 Reproductive aging
 Cycle day 3 serum FSH and estradiol
 Abnormal (“diminished ovarian reserve”)
 FSH > 10 IU/L
 Estradiol > 75-80 pg/mL
 Clomiphene citrate challenge test
 Cycle day 10 serum FSH
 Serum antimullerian hormone (AMH)
Idiopathic Infertility
 Prevalence ~ 15%
 Factors that cannot be identified
 Sperm transport defects
 Inability of sperm to fertilize egg
 Implantation defects
Infertility: Management
 Male Factor
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Avoidance of alcohol
Scheduled intercourse
Ligation of venous plexus for significant varicocele
Intrauterine insemination (IUI) with washed sperm
Intracytoplasmic sperm injection (ICSI) + IVF
Donor sperm insemination
Infertility: Management
 Anovulation
 Oral medications:
 Clomiphene citrate
 Dopamine agonists (Bromocriptine) - hyperprolactinemia
 Injectable medications:
 Gonadotropins (FSH/hMG, hCG)
 Laparoscopic “ovarian drilling”
 Complications: Ovarian hyperstimulation, Multiple pregnancy
Infertility: Management
 Reproductive tract abnormality
 Uterine: Myomectomy, Septoplasty, Adhesiolysis
 Tubal: Microsurgical tuboplasty, Neosalpigostomy
 Peritoneal: Laparascopic treatment of endometriosis, Adhesiolysis
 Idiopathic infertility
 Ovarian stimulation + IUI
 Clomiphene or gonadotropins (hMG, hCG)
 IVF
Infertility: Management (IVF)
 Used for:
 Severe male factor
 Tubal disease
 Couples who failed other treatments
 Requires
 Controlled ovarian hyperstimulation
 Retrieval of oocytes
 In vitro fertilization and embryo transfer
 Procedures
 IVF + embryo transfer (IVF-ET)
 Intracytoplasmic sperm injection + embryo transfer (ICSI-ET)
 Donor egg IVF + embryo transfer
Psychological
 The psychological stress associated with
infertility must be recognized and patients
should be counseled appropriately.
Bottom Line Concepts
 Infertility is defined as one year of unprotected coitus without
conception. Infertility may be primary or secondary.
 Multiple causes must be considered for infertility diagnosis and
treatment.
 Male and female reproductive tract anatomy and physiology should be
reviewed in order to generate a full differential diagnosis.
 Components of an initial infertility workup include a thorough history
and physical examination. Laboratory investigations include a semen
analysis, documentation of ovulation, and hysterosalpingogram.
 Dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis and
medical illness, including thyroid disease and pituitary tumors, can
cause ovulatory disturbances.
 Success rates with IVF depend on the etiology of infertility and the age
of the female partner.
References and Resources
 APGO Medical Student Educational Objectives, 9th edition, (2009),
Educational Topic 48 (p102-103).
 Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010),
Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William
NP Herbert, Douglas W Laube, Roger P Smith. Chapter 38 (p337-346).
 Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and
Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone,
Calvin J Hobel. Chapter 34 (p371-378).