Infertility

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Infertility

• David Toub, M.D.
• Medical Director
• Newton Interactive

2
Definitions

• Infertility
• Inability to conceive after one year of
  unprotected intercourse (6 months for women over
  35?)
• Fertility
• Ability to conceive
• Fecundity
• Ability to carry to delivery

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Statistics

• 80 of couples will conceive within 1 year of
  unprotected intercourse
• 86 will conceive within 2 years
• 14-20 of US couples are infertile by definition
  (3 million couples)
• Origin
• Female factor 40
• Male factor 30
• Combined 30

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Etiologies

• Sperm disorders 30.6
• Anovulation/oligoovulation 30
• Tubal disease 16
• Unexplained 13.4
• Cx factors 5.2
• Peritoneal factors 4.8

5
Associated Factors

• PID
• Endometriosis
• Ovarian aging
• Spermatic varicocoele
• Toxins
• Previous abdominal surgery (adhesions)
• Cervical/uterine abnormalities
• Cervical/uterine surgery
• Fibroids

6
Emotional and Educational Needs

• Disease of couples, not individuals
• Feelings of guilt
• Where to go for information?
• Options
• Feelings of frustration and anger
• Support groups (e.g. Resolve)

7
Overview of Evaluation

• Female
• Ovary
• Tube
• Corpus
• Cervix
• Peritoneum
• Male
• Sperm count and function
• Ejaculate characteristics, immunology
• Anatomic anomalies

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The Most Important Factor in the Evaluation of
the Infertile Couple Is
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HISTORY
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History-General

• Both couples should be present
• Age
• Previous pregnancies by each partner
• Length of time without pregnancy
• Sexual history
• Frequency and timing of intercourse
• Use of lubricants
• Impotence, anorgasmia, dyspareunia
• Contraceptive history

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History-Male

• History of pelvic infection
• Radiation, toxic exposures (include drugs)
• Mumps
• Testicular surgery/injury
• Excessive heat exposure (spermicidal)

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History-Female

• Previous female pelvic surgery
• PID
• Appendicitis
• IUD use
• Ectopic pregnancy history
• DES (?relation to infertility)
• Endometriosis

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History-Female

• Irregular menses, amenorrhea, detailed menstrual
  history
• Vasomotor symptoms
• Stress
• Weight changes
• Exercise
• Cervical and uterine surgery

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When Not to Pursue an Infertility Evaluation

• Patient not sexually-active
• Patient not in long-term relationship?
• Patient declines treatment at this time
• Couple does not meet the definition of an
  infertile couple

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Physical Exam-Male

• Size of testicles
• Testicular descent
• Varicocoele
• Outflow abnormalities (hypospadias, etc)

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Physical Exam-Female

• Pelvic masses
• Uterosacral nodularity
• Abdominopelvic tenderness
• Uterine enlargement
• Thyroid exam
• Uterine mobility
• Cervical abnormalities

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Overall Guidelines for Work-up

• Timeliness of testing-w/u can usually be
  accomplished in 1-2 cycles
• Timing of tests
• Dont over test
• Cut to the chase, i.e. proceed with laparoscopy
  if adhesive disease is likely

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Work-up by Organ Unit
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Ovary
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Ovarian Function

• Document ovulation
• BBT
• Luteal phase progesterone
• LH surge
• EMBx
• If POF suspected, perform FSH
• TSH, PRL, adrenal functions if indicated
• The only convincing proof of ovulation is
  pregnancy

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Ovarian Function

• Three main types of dysfunction
• Hypogonadotrophic, hypoestrogenic (central)
• Normogonadotrophic, normoestrogenic (e.g. PCOS)
• Hypergonadotrophic, hypoestrogenic (POF)

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BBT

• Cheap and easy, but
• Inconsistent results
• Provides evidence after the fact (like the old
  story about the barn door and the horse)
• May delay timely diagnosis and treatment
• 98 of women will ovulate within 3 days of the
  nadir
• Biphasic profiles can also be seen with LUF
  syndrome

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Luteal Phase Progesterone

• Pulsatile release, thus single level may not be
  useful unless elevated
• Performed 7 days after presumptive ovulation
• Done properly, gt15 ng/ml consistent with
  ovulation

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Urinary LH Kits

• Very sensitive and accurate
• Positive test precedes ovulation by 24 hours, so
  useful for timing intercourse
• Downside price, obsession with timing of
  intercourse

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Endometrial Biopsy

• Invasive, but the only reliable way to diagnose
  LPD
• ??Is LPD a genuine disorder???
• Pregnancy loss rate lt1
• Perform around 2 days before expected
  menstruation ( day 28 by definition)
• Lag of gt2 days is consistent with LPD
• Must be done in two different cycles to confirm
  diagnosis of LPD

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Fallopian Tubes
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Tubal Function

• Evaluate tubal patency whenever there is a
  history of PID, endometriosis or other
  adhesiogenic condition
• Kartageners syndrome can be associated with
  decreased tubal motility
• Tests
• HSG
• Laparoscopy
• Falloposcopy (not widely available)

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Hysterosalpingography (HSG)

• Radiologic procedure requiring contrast
• Performed optimally in early proliferative phase
  (avoids pregnancy)
• Low risk of PID except if previous history of PID
  (give prophylactic doxycycline or consider
  laparoscopy)
• Oil-based contrast
• Higher risk of anaphylaxis than H2O-based
• May be associated with fertility rates

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Hysterosalpingography (HSG)

• Can be uncomfortable
• Pregnancy test is advisable
• Can detect intrauterine and tubal disorders but
  not always definitive

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Laparoscopy

• Invasive requires OR or office setting
• Can offer diagnosis and treatment in one sitting
• Not necessary in all patients
• Uses (examples)
• Lysis of adhesions
• Diagnosis and excision of endometriosis
• Myomectomy
• Tubal reconstructive surgery

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Falloposcopy

• Hysteroscopic procedure with cannulation of the
  Fallopian tubes
• Can be useful for diagnosis of intraluminal
  pathology
• Promising technique but not yet widespread

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Uterine Corpus
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Corpus

• Asherman Syndrome
• Diagnosis by HSG or hysteroscopy
• Usually s/p DC, myomectomy, other intrauterine
  surgery
• Associated with hypo/amenorrhea, recurrent
  miscarriage
• Fibroids, Uterine Anomalies
• Rarely associated with infertility
• Work-up
• Ultrasound
• Hysteroscopy
• Laparoscopy

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Cervix
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Cervical Function

• Infection
• Ureaplasma suspected
• Stenosis
• S/P LEEP, Cryosurgery, Cone biopsy (probably
  overstated)
• Immunologic Factors
• Sperm-mucus interaction

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Cervical Function

• Tests
• Culture for suspected pathogens
• Postcoital test (PK tests)
• Scheduled around 1-2d before ovulation (increased
  estrogen effect)
• 480 of male abstinence before test
• No lubricants
• Evaluate 8-12h after coitus (overnight is ok!)
• Remove mucus from cervix (forceps, syringe)

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Cervical Function

• PK, continued (normal values in yellow)
• Quantity (very subjective)
• Quality (spinnbarkeit) (gt8 cm)
• Clarity (clear)
• Ferning (branched)
• Viscosity (thin)
• WBCs (0)
• progressively motile sperm/hpf (5-10/hpf)
• Gross sperm morphology (WNL)

Male factors
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Problems with the PK test

• Subjective
• Timing varies may need to be repeated
• In some studies, infertile couples with an
  abnormal PK conceived successfully during that
  same cycle

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Peritoneum
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Peritoneal Factors

• Endometriosis
• 2x relative risk of infertility
• Diagnosis (and best treatment) by laparoscopy
• Can be familial can occur in adolescents
• Etiology unknown but likely multiple ones
• Retrograde menstruation
• Immunologic factors
• Genetics
• Bad karma
• Medical options remain suboptimal

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Male Factors
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Male Factors

• Serum T, FSH, PRL levels
• Semen analysis
• Testicular biopsy
• Sperm penetration assay (SPA)

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Male Factors-Semen Analysis

• Collected after 480 of abstinence
• Evaluated within one hour of ejaculation
• If abnormal parameters, repeat twice, 2 weeks
  apart

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Normal Semen Analysis
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Sperm Penetration Assay

• aka zona-free hamster ova assay
• Dynamic test of fertilization capacity of sperm
• Failure to penetrate at least 10 of zona-free
  ova consistent with male factor
• False positives and negatives exist

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Treatment Options
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Ovarian Disorders

• Anovulation
• Clomiphene Citrate hCG
• hMG
• Induction IUI (often done but unjustified)
• PRL
• Bromocriptine
• TSS if macroadenoma
• POF
• ?high-dose hMG (not very effective)

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Ovarian Disorders

• Central amenorrhea
• CC first, then hMG
• Pulsatile GnRH
• LPD
• Progesterone suppositories during luteal phase
• CC hCG

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Ovarian Matrix
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Ovulation Induction

• CC
• 70 induction rate, 40 pregnancy rate
• Patients should typically be normoestrogenic
• Induce menses and start on day 5
• With dosages, antiestrogen effects dominate
• Multifetal rates 5-10
• Monitor effects with PK, pelvic exam

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hMG (Pergonal)

• LH FSH (also FSH alone Metrodin)
• For patients with hypogonadotrophic
  hypoestrogenism or normal FSH and E2 levels
• Close monitoring essential, including estradiol
  levels
• 60-80 pregnancy rates overall, lower for PCOS
  patients
• 10-15 multifetal pregnancy rate

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Risks

• CC
• Vasomotor symptoms
• H/A
• Ovarian enlargement
• Multiple gestation
• NO risk of SAb or malformations

• hMG
• Multiple gestation
• OHSS (1)
• Can often be managed as outpatient
• Diuresis
• Severe cases fatal if untreated in ICU setting

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Fallopian Tubes

• Tuboplasty
• IVF
• GIFT, ZIFT not options

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Corpus

• Asherman syndrome
• Hysteroscopic lysis of adhesions (scissor)
• Postop Abx, E2
• Fibroids (rarely need treatment)
• Myomectomy(hysteroscopic, laparoscopic, open)
• ??UAE
• Uterine anomalies (rarely need treatment)
• metroplasty

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Cervix

• Repeat PK test to rule out inaccurate timing of
  test
• If cervicitis Abx
• If scant mucus low-dose estrogen
• Sperm motility issues (? Antisperm ABs)
• Steroids?
• IUI

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Peritoneum (Endometriosis)

• From a fertility standpoint, excision beats
  medical management
• Lysis of adhesions
• GnRH-a (not a cure and has side effects,
  expense)
• Danazol (side effects, cost)
• Continuous OCPs (poor fertility rates)
• Chances of pregnancy highest within 6 mos-1 year
  after treatment

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Male Factor

• Hypogonadotrophism
• hMG
• GnRH
• CC, hCG results poor
• Varicocoele
• Ligation? (no definitive data yet)
• Retrograde ejaculation
• Ephedrine, imipramine
• AIH with recovered sperm

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Male Factor

• Idiopathic oligospermia
• No effective treatment
• ?IVF
• donor insemination

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Unexplained Infertility

• 5-10 of couples
• Consider PRL, laparoscopy, other hormonal tests,
  cultures, ASA testing, SPA if not done
• Review previous tests for validity
• Empiric treatment
• Ovulation induction
• Abx
• IUI
• Consider IVF and its variants
• Adoption

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Summary

• Infertility is a common problem
• Infertility is a disease of couples
• Evaluation must be thorough, but individualized
• Treatment is available, including IVF, but can be
  expensive, invasive, and of limited efficacy in
  some cases
• Consultation with a BC/BE reproductive
  endocrinologist is advisable

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Thank you!