Transcript Infertility: Definition, diagnosis and treatment options

Infertility: Definition,
diagnosis and
treatment options
Emalee Danforth, CNM
University Reproductive Care
University of Washington
Infertility Definition
• “Infertility is a disease defined by the failure to achieve a
successful pregnancy after 12 months or more of appropriate,
timed unprotected intercourse or therapeutic donor
insemination. Earlier evaluation and treatment may be
justified based on medical history and physical findings and is
warranted after 6 months for women over age 35 years.”
• ASRM Practice Committee Opinion, 2013
Infertility Incidence
• Infertility is experienced by 15% of couples.
• This rate is likely higher in developing countries given the
higher burden of infectious and chronic disease.
Infertility Evaluation
• 85-90% of infertility can be explained through the evaluation
of 3 primary factors
• 1) Sperm – semen analysis
• 2) Tubal patency – hysterosalpingogram (HSG)
• 3) Ovarian reserve and ovulatory function
• Also evaluate thyroid, prolactin, vitamin D
Ovary on cycle day 2-4
Ovarian Reserve evaluation
• Follicle Stimulating Hormone (FSH)
• Cycle day 2-4, <10 is considered WNL
• Anti-Mullerian Hormone (AMH)
• Between 1-3 is considered normal, but not a definite range of
normal
• Antral Follicle Count (AFC)
• Range 7-15 is WNL but not absolute
• There is no one perfect test for ovarian reserve, look at the
whole picture
• Age of female partner is the biggest independent
prognosticator for the likelihood of achieving pregnancy
Age & Fertility Relationship
Cycle day 2-4 follicular
monitoring
Polycystic ovary
Ovulatory Function
• Taking a thorough menstrual history is key to determining if a
patient is ovulatory
• Obtain details such as cycle length range, number of days of
bleeding, occurrence of cramps, amount of bleeding, spotting
preceding cycle
• Regular monthly menstrual cycles with consistent moliminal
symptoms are strongly correlated with ovulatory cycles
• Irregular or absent cycles or cycles >35 days indicate likely
anovulation or oligo-ovulation.
• Luteal phase progesterone level >3 confirms ovulation. Check
7 days after ovulation/7 days before the expected onset of
next menses
Semen Analysis
• 4 primary factors
• Volume >1.45ml
• Concentration >14 million/ml
• Motility >39%
• Progressive >31%
• Rapid & linear >11%
• Morphology >4% by strict Krueger criteria
• Progressive motile sperm per ejaculate >12.4 million
Semen Analysis example
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Component Results
543 4671
Component
Testing Location:
Value
Range & Units
Status
Male Fertility Laboratory, Department of Urology. 206
Abstinence From Ejaculation
6 (H)
2 - 5 days
Collect To Analysis Time
34
20 - 60 min
Semen Volume
4.3
>1.45 mL
Semen Volume
WHO 2010
Sperm Concentration 63
>14 mil sperm/mL
Sperm Concentration WHO 2010
Sperm Motility
30 (L)
>39 %
Sperm Motility
(WHO category a+b+c)
Sperm Motility
WHO 2010
Progressive Motility, %
22 (L)
>31 %
Progressive Motility, %
WHO Categories a+b: Rapid and slow progressive sperm
Progressive Motility, %
WHO 2010
Rapid & Linear Motility, Comp
2 (L)
>11 %
Strict Normal Morphology
1 (L)
>3.9 %
Strict Normal Morphology
TYGSC using WHO 2010. Note: Guzick et al 2001 (NEJM
345:1388) consider <9% infertile, 9-12% indeterminate.
Round Cells (WBC & Immature Germ)
3300 (H)
0 - 1000 CELLS/microL
Round Cells (WBC & Immature Germ)
Reflexive Differential performed to calculate WBC
concentration
Progr Mot Sperm Per Ejac, Mill
60
>12.4 mil/ejaculate
Progr Mot Sperm Per Ejac, Mill
WHO 2010
Semen Other Abnormal Findings
Much debris, pH 8.7.
Semen Other Abnormal Findings
Normal pH 7.8 to 8.6
Semen Other Abnormal Findings
Incomplete liquefaction
Notes:
ASTHENOTERATOZOOSPERMIA
Notes:
Reference: World Health Organization, WHO laboratory
manual for the examination and processing of human
semen (5th ed.) Cambridge, U.K., Cambridge University
Press, 2010.
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This sample demonstrates low motility and low morphology =
asthenoteratozoospermia
Normal HSG Image
Optimal view of the uterus, no filling defects, normal uterine shape
Fallopian tubes demonstrate clear bilateral “fill & spill”
Suboptimal image of HSG
Uterus is dextrorotated, sub-optimal view of the uterus
Able to see bilateral “fill & spill”
HSG with filling defect
Irregular pattern upon filling within the uterus- suggests polyps
This image is taken prior to the fallopian tubes filling
HSG demonstrating tubal
obstruction
Right proximal tubal obstruction. Fill & spill of left tube only.
In addition, left LUS filling defect c/w polyp vs. fibroid
Treatment options
• Correct or improve underlying etiology if possible
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Hyperprolactinemia
Thyroid disorder
Weight loss
PCOS management
Surgical treatment of endometriosis or structural anomalies
Treatment for reversible causes of male factor
Treatment options
• “Low-Tech”
• Oral ovulation induction agents
• Clomiphene Citrate (Clomid), a selective estrogen receptor
modulator (SERM)
• Letrozole (Femara), an aromatase inhibitor
• Controlled ovarian hyperstimulation/Gonadotropin
• Follicle stimulating hormone (Gonal-F)
• FSH & LH (Menopur)
• Intra-uterine insemination
Indications for low-tech
• No absolute indication for IVF
• Treatment of oligo- or anovulation
• Treatment for unexplained infertility, mild male factor,
diminished ovarian reserve
• Used for women that are not good candidates for IVF and
decline use of donor egg
• To increase per cycle chance of conception with use of donor
sperm
Ovulation Induction Agents
Gonadotropins
Mature Follicle
Midcycle follicular monitoring
Midcycle Trilaminar lining
Treatment options
• Assisted Reproductive Technology (ART)
• In Vitro Fertilization (IVF)
• Use of patient’s own egg or donor egg
• Use of patient’s own uterus or a gestational carrier
• Intra-cytoplasmic sperm insemination (ICSI)
Indications for ART
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Severe male factor
Tubal factor
Failure to achieve pregnancy with low-tech options
Desire to create embryos for future use
• Oncofertility
• Social reasons
• Egg freezing
• Genetic indications
• Prenatal genetic screening or diagnosis
ART steps
• ART is a general term for any reproductive assistance that
involved removing the egg from the body.
• In IVF the female patient uses hyperphysiologic levels of
gonadotropins to hyperstimulate the ovary and bring as many
eggs to maturity simultaneously as possible.
• The eggs are then surgically removed and fertilized with
sperm in the lab setting. This is done either by ICSI or
conventional insemination
• The embryos are grown in culture in the lab setting for a fresh
transfer back to the uterus either on day 3 or 5, or for freezing
on day 5 or 6.
Embryos are transferred back to the uterus at either Day 3 or Day 5.
Day 5 has higher success rates – thought to be because the best embryos
have “selected out.”
SART National Data Summary 2012
Age of the female patient
Number of cycles
Percentage of cycles resulting in pregnancies
Percentage of cycles resulting in live births
Reliability Range
Percentage of retrievals resulting in live births
Percentage of transfers resulting in live births
Percentage of cycles with elective single embryo transfer
Percentage of cancellations
Implantation Rate
Average number of embryos transferred
Percentage of live births with twins
Percentage of live births with triplets or more
<35
35-37
38-40
41-42
>42
38662
19599
18410
10167
6224
46.7
37.8
29.7
19.8
8.6
40.7
31.3
22.2
11.8
3.9
(40.2 - 41.1) (30.7 - 32.0) (21.6 - 22.8) (11.2 - 12.4) (3.5 - 4.4)
43.4
34.5
25.4
14
5
47.1
37.9
28.5
16.3
6.1
14.8
8.9
3
1.2
0.6
6.3
9.2
12.7
15.8
21.5
37.5
27.6
18.4
9.8
3.8
1.9
2
2.4
2.9
2.9
29.5
25
20.3
13.4
9
1.1
0.7
0.7
0.7
0.4
Resources
• ASRM.org
• SART.org
• My contact information is [email protected] and you are
welcome to email me with questions about infertility and
fertility treatments.