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Infertility

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If POF suspected, perform FSH. TSH, PRL, adrenal functions if indicated ... Hypergonadotrophic, hypoestrogenic (POF) BBT. Cheap and easy, but... Inconsistent results ... – PowerPoint PPT presentation

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Title: Infertility


1
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

3
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

4
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

8
The Most Important Factor in the Evaluation of
the Infertile Couple Is
9
HISTORY
10
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

11
History-Male
  • History of pelvic infection
  • Radiation, toxic exposures (include drugs)
  • Mumps
  • Testicular surgery/injury
  • Excessive heat exposure (spermicidal)

12
History-Female
  • Previous female pelvic surgery
  • PID
  • Appendicitis
  • IUD use
  • Ectopic pregnancy history
  • DES (?relation to infertility)
  • Endometriosis

13
History-Female
  • Irregular menses, amenorrhea, detailed menstrual
    history
  • Vasomotor symptoms
  • Stress
  • Weight changes
  • Exercise
  • Cervical and uterine surgery

14
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

15
Physical Exam-Male
  • Size of testicles
  • Testicular descent
  • Varicocoele
  • Outflow abnormalities (hypospadias, etc)

16
Physical Exam-Female
  • Pelvic masses
  • Uterosacral nodularity
  • Abdominopelvic tenderness
  • Uterine enlargement
  • Thyroid exam
  • Uterine mobility
  • Cervical abnormalities

17
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

18
Work-up by Organ Unit
19
Ovary
20
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

21
Ovarian Function
  • Three main types of dysfunction
  • Hypogonadotrophic, hypoestrogenic (central)
  • Normogonadotrophic, normoestrogenic (e.g. PCOS)
  • Hypergonadotrophic, hypoestrogenic (POF)

22
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

23
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

24
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

25
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

26
Fallopian Tubes
27
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)

28
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

29
Hysterosalpingography (HSG)
  • Can be uncomfortable
  • Pregnancy test is advisable
  • Can detect intrauterine and tubal disorders but
    not always definitive

30
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

31
Falloposcopy
  • Hysteroscopic procedure with cannulation of the
    Fallopian tubes
  • Can be useful for diagnosis of intraluminal
    pathology
  • Promising technique but not yet widespread

32
Uterine Corpus
33
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

34
Cervix
35
Cervical Function
  • Infection
  • Ureaplasma suspected
  • Stenosis
  • S/P LEEP, Cryosurgery, Cone biopsy (probably
    overstated)
  • Immunologic Factors
  • Sperm-mucus interaction

36
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)

37
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
38
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

39
Peritoneum
40
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

41
Male Factors
42
Male Factors
  • Serum T, FSH, PRL levels
  • Semen analysis
  • Testicular biopsy
  • Sperm penetration assay (SPA)

43
Male Factors-Semen Analysis
  • Collected after 480 of abstinence
  • Evaluated within one hour of ejaculation
  • If abnormal parameters, repeat twice, 2 weeks
    apart

44
Normal Semen Analysis
45
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

46
Treatment Options
47
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)

48
Ovarian Disorders
  • Central amenorrhea
  • CC first, then hMG
  • Pulsatile GnRH
  • LPD
  • Progesterone suppositories during luteal phase
  • CC hCG

49
Ovarian Matrix
50
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

51
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

52
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

53
Fallopian Tubes
  • Tuboplasty
  • IVF
  • GIFT, ZIFT not options

54
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

55
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

56
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

57
Male Factor
  • Hypogonadotrophism
  • hMG
  • GnRH
  • CC, hCG results poor
  • Varicocoele
  • Ligation? (no definitive data yet)
  • Retrograde ejaculation
  • Ephedrine, imipramine
  • AIH with recovered sperm

58
Male Factor
  • Idiopathic oligospermia
  • No effective treatment
  • ?IVF
  • donor insemination

59
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

60
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

61
Thank you!
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