Basic Investigation of an Infertile Couple
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Basic Investigation of Infertile Couple
Leedah Ranola-Nisperos, MD,
FPOGS, FPSREI, FPSGE
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Infertility inability of a couple to conceive after
one year of unprotected intercourse
◦primary: no previous pregnancies have occurred
◦ secondary: a prior pregnancy has occurred
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Infertility therefore affects approximately 10-15% of couples and is important part of the practice of many clinicians.
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Subfertility Couples who are not sterile but
exhibit decreased reproductive efficiency.
Fecundability- probability that a cycle will result in pregnancy
Fecundity- probability that a cycle will result in live birth
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Time of
Exposure
% Pregnant
3 months 57%
6 months 72%
1 year 85%
2 years 93%
Time Required for Conception in Couples Who Will Attain Pregnancy
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greater focus on education and career among women delayed childbearing
decreased family size
increased awareness of available therapies (ART)
improvements in contraception and access to family planning services
later marriage and frequent divorce/separation
increased incidence of sexually transmitted disease (STDs)
Epidemiology of Infertility
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Aging and Reproduction in Women
100
80
60
40
20
0
50
40
30
20
10
0
20-24 25-29 30-34 35-39 40-44
Percent of maximum fertility Miscarriage rate (%)
Miscarriage rate (percentage) Percent of maximum fertility
Speroff 7th ed.
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Natural Conception
“ People who are concerned about their
fertility should be informed that female infertility declines with age, but that the effect of age on male fertility is less clear. ”
“ With regular unprotected sexual intercourse, 94% of fertile women aged 35 years, and 77% of those aged 38 years, will conceive after 3 years of trying.”
(NICE Feb. 2004) C (Evidence level 4)
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Ovarian Reserve ◦ size and quality of the remaining ovarian follicular pool
◦ provide prognostic information that can help to guide the choice of treatment and best use of available resources
Age and Decreased Ovarian Reserve
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Ovarian Reserve tests
Day 3 serum FSH/estradiol levels
Clomiphene citrate challenge test (CCCT)
Antral follicle count
Antimullerian hormone (AMH)
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Day 3 serum FSH
◦ simplest and most widely applied measure of ovarian reserve
◦ abnormal: above 10-15 IU/L
Day 3 estradiol >80 pg/ml
◦ early elevations reflect
advanced follicular
development and early
selection of a dominant follicle
driven by rising FSH levels in
older cycling women
Ovarian Reserve Tests
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CCCT ◦ provocative and even more sensitive test
◦ cycle day 3 FSH and estradiol and cycle day 10 FSH after treatment with clomiphene citrate 100 mg/day, cycle days 5-9
◦ less inhibin B and estradiol in aging women-> less negative feedback inhibition on clomiphene-induced pituitary FSH release
◦ likelihood of pregnancy, inversely related to both the cycle day 3 and day 10 FSH
Ovarian Reserve Tests
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◦ reflects the size of the resting follicular pool
◦ 2 to 8 mm diameter
◦ correlates with age and response to gonadotropin stimulation
◦ 10 follicles associated with increased risk of cycle cancellation
Antral follicle count (TVS), early follicular phase
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◦ produced by granulosa cells of preantral and small antral follicles
◦ decreased primordial follicle count with increasing age
◦ value <0.2 ng/mL: poor ovarian reserve
Antimullerian hormone (AMH)
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Ovarian reserve testing is indicated in the following patients:
age older than 35
unexplained infertility, regardless of age
family history of early menopause
previous ovarian surgery (cystectomy/drilling, unilateral oophorectomy, chemotherapy, radiation)
smoking
demonstrated poor response to exogenous gonadotropin stimulation
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Goals in the Evaluation of Infertility
identify and correct specific causes of infertility
provide accurate information and to dispel the misinformation
provide emotional support during a trying time
provide alternatives to couples who do not achieve success with standard forms of treatment
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all couples who failed to conceive after a year or more of unprotected intercourse
immediate evaluation: ◦ age >35
◦ women with history of oligomenorrhea/amenorrhea
◦ women with known or suspected pelvic pathology
( PID/endometriosis)
◦ men with known or suspected poor semen quality
When should formal evaluation of infertility begin?
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Female Fertility Evaluation
History
◦ gravidity, parity, pregnancy outcomes and associated complications
◦ cycle length and characteristics, onset and severity of dysmenorrhea
◦ coital frequency, and any sexual dysfunction
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Female Fertility Evaluation
History ◦ duration of infertility and results of any previous evaluation and treatment
◦ past surgery and past or current medical illnesses (PID, STDs)
◦ previous abnormal pap smears and any subsequent treatment
◦ current medications and allergies
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Female Fertility Evaluation
History occupation and use of tobacco, alcohol, and
other drugs
family history of birth defects, mental retardation, early menopause or reproductive failure
symptoms of thyroid disease, pelvic or abdominal pain, galactorrhea, hirsutism, and dyspareunia
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Smoking
“ Women who smoke should be informed that this is likely to reduce their fertility.”
(NICE Feb. 2004)
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Female Fertility Evaluation
Physical Examination
◦ weight and body mass index
◦ any thyroid enlargement, nodule, tenderness
◦ breast secretions and their character
◦ signs of androgen excess
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Female Fertility Evaluation
Physical Examination
◦ pelvic or abdominal tenderness, organ enlargement or mass
◦ vaginal or cervical abnormality, secretions, or discharge
◦ any mass, tenderness, or nodularity in the adnexa or cul-de-sac
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Body Weight
“Women who have a BMI of >29 should be informed that they are likely to take longer to conceive.”
(NICE Feb. 2004)
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Male Fertility Evaluation
History ◦ prior paternity ◦ cryptorchidism, hypospadias or retrograde ejaculation
◦ testicular surgery, genital radiation, chemotherapy
◦ sexual dysfunction ◦ diabetes, postpubertal mumps ◦ medications, drugs, alcohol, tobacco abuse
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Alcohol
“Men should be informed that excessive alcohol intake is detrimental to semen quality.”
(NICE Feb. 2004)
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“Men who smoke should be informed that there is an association between smoking and reduced semen quality and that stopping smoking will improve their general health.”
(NICE Feb. 2004)
Smoking
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Male Fertility Evaluation
Physical Examination
◦ testicular descent, size and consistency
◦ varicocoele or penile anomalies
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Causes of Infertility (Speroff 7th ed)
COUPLES
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Tubal and pelvic
pathology40%
Ovulatorydysfunction
40%
Unexplained infertility10%
Unusual problems10%
WOMEN
Causes of Infertility (Speroff 7th edition)
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Semen analysis
Confirmation of ovulation
Documentation of tubal patency
Basic Investigations of Infertile Couple
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Lower reference limits (5th percentiles and their 95% confidence intervals) for semen characteristics
Parameter Lower reference limit
Semen volume (ml) 1.5 (1.4 – 1.7)
Total sperm number (106 per
ejaculate)
39 (33 – 46)
Sperm concentration (106 per ml) 15 (12 – 16)
Total motility (PR + NP, %) 40 (38 – 42)
Progressive motility (PR, %) 32 (31 – 34)
Vitality (live spermatozoa, %) 58 (55 – 63)
Sperm morphology (normal forms, %) 4 (3.0 – 4.0)
(WHO, 5th edition 2010)
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Semen Analysis
advised to abstain from ejaculation for 2-3 days before collection
collect specimen in a clean, wide-mouthed jar
specimen should be kept warm during transport to the laboratory
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male fertility peaks at age 35 and declines sharply at age 45
increase aneuploid sperm with advance paternal age >55 years
increasing age accompanied by reduced female fecundity
age-related decline in gamete quality among men subtler than that observed in aging women
Aging and Male Fertility
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Menstrual History
Ovulatory Anovulatory
• regular, predictable
• consistent in volume
and duration
• moliminal symptoms
• Irregular,
unpredictable,
infrequent
• vary in flow
characteristics
• inconsistent pattern
of molimina
Ovulatory Factor
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Assessing ovulation
“Women with regular monthly menstrual cycles should be informed that they are likely to be ovulating”
(NICE Feb. 2004)
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Ovulatory Factor
most easily diagnosed and most treatable causes of infertility
Tests: ◦ Basal Body Temperature (BBT)
◦ Midluteal serum progesterone
◦ Urinary LH excretion
◦ Ultrasound monitoring
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Basal Body Temperature (BBT):
◦ least expensive and non-invasive method
◦ thermogenic action of progesterone, 0.4º-0.8ºF over the baseline
◦ presumptive evidence of ovulation can be identified retrospectively
Confirmatory tests of Ovulation
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Confirmatory tests of Ovulation
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Assessing ovulation
“The use of BBT charts to confirm ovulation does not reliably predict ovulation and is not recommended.”
(NICE Feb. 2004)
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Confirmatory tests of Ovulation
Midluteal serum progesterone ◦ taken days 21-23 of an ideal 28-day cycle
◦ ovulation occurred: >3 ng/mL
◦ optimum luteal function: >10 ng/mL
Urinary LH ◦ document LH surge to predict ovulation
◦ ovulation occurs 34-36 hours after LH surge, 10-12 hours after LH peak
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Confirmatory tests of Ovulation
Ultrasound monitoring
◦ serial monitoring of a dominant follicle till ovulation occurs
◦ provides the most accurate estimate of when ovulation occurs
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Documentation of Tubal Patency
Hysterosalpingo-graphy (HSG)
Laparoscopy with Chromopertubation
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Hysterosalpingography (HSG)
Normal HSG
Hydrosalpinx
• images the uterine cavity and reveals the internal architecture of the tubal lumen • performed as out-patient basis
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Hysterosalpingography (HSG)
Normal HSG
Hydrosalpinx
• Done during the week following the end of menses
• Prophylactic doxycycline 100 mg BID for 4 days, start day 1 before the procedure • 85-100% sensitivity, 90% specificity
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Laparoscopy with Chromopertubation
Patent tube Hydrosalpinx PID
– provides detailed information about the pelvic anatomy
– most thorough technique for diagnosing tubal and peritoneal disease
• more invasive, requires anesthesia
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Assessing Tubal Damage
“Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time.
(NICE Feb. 2004)
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Uterine factor of female infertility
Anatomic
abnormalities
Functional
abnormality
• Congenital
malformations
• Leiomyomas/
endometrial polyps
• Intrauterine
adhesions
•Chronic
endometritis
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Basic Methods for the Evaluation of Uterine Factor
Hysterosalpingogram (HSG)
TVS or SIS
Hysteroscopy
MRI
bicornuate uterus septum myoma
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Assessing Uterine Abnormalities
“Women should not be offered hysteroscopy on its own as part of the initial investigation unless clinically indicated because the effectiveness of surgical treatment of uterine abnormalities on improving pregnancy rates has not been established.
(NICE Feb. 2004)
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Cervical Factor
Post-coital testing of cervical mucus “Its routine use in the investigation of
fertility problems is not recommended because it has no predictive value on pregnancy rate.”
(NICE Feb. 2004)
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Unexplained Infertility
Normal standard infertility evaluation
◦ Semen analysis
◦ Assessment of ovulation
◦ HSG
15-30% of couples
Additional tests:
◦ Laparoscopy:
unrecognized peritoneal factors (endometriosis/pelvic adhesions)
◦ Ovarian reserve assessment
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Thank You!