Basic Investigation of an Infertile Couple

Basic Investigation of Infertile Couple

Leedah Ranola-Nisperos, MD,

FPOGS, FPSREI, FPSGE

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

Infertility therefore affects approximately 10-15% of couples and is important part of the practice of many clinicians.

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

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

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

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.

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)

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

Ovarian Reserve tests

Day 3 serum FSH/estradiol levels

Clomiphene citrate challenge test (CCCT)

Antral follicle count

Antimullerian hormone (AMH)

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

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

◦ 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

◦ 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)

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

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

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?

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


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


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

Smoking

“ Women who smoke should be informed that this is likely to reduce their fertility.”

(NICE Feb. 2004)


Physical Examination

◦ weight and body mass index

◦ any thyroid enlargement, nodule, tenderness

◦ breast secretions and their character

◦ signs of androgen excess



◦ 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

Body Weight

“Women who have a BMI of >29 should be informed that they are likely to take longer to conceive.”

(NICE Feb. 2004)

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

Alcohol

“Men should be informed that excessive alcohol intake is detrimental to semen quality.”

(NICE Feb. 2004)

“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

Male Fertility Evaluation


◦ testicular descent, size and consistency

◦ varicocoele or penile anomalies

Causes of Infertility (Speroff 7th ed)

COUPLES

Tubal and pelvic

pathology40%

Ovulatorydysfunction

40%

Unexplained infertility10%

Unusual problems10%

WOMEN

Causes of Infertility (Speroff 7th edition)

Semen analysis

Confirmation of ovulation

Documentation of tubal patency

Basic Investigations of Infertile Couple

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)

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

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

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

Assessing ovulation

“Women with regular monthly menstrual cycles should be informed that they are likely to be ovulating”

(NICE Feb. 2004)

Ovulatory Factor

most easily diagnosed and most treatable causes of infertility

Tests: ◦ Basal Body Temperature (BBT)

◦ Midluteal serum progesterone

◦ Urinary LH excretion

◦ Ultrasound monitoring

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

Assessing ovulation

“The use of BBT charts to confirm ovulation does not reliably predict ovulation and is not recommended.”

(NICE Feb. 2004)


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


Ultrasound monitoring

◦ serial monitoring of a dominant follicle till ovulation occurs

◦ provides the most accurate estimate of when ovulation occurs

Documentation of Tubal Patency

Hysterosalpingo-graphy (HSG)

Laparoscopy with Chromopertubation

Hysterosalpingography (HSG)

Normal HSG

Hydrosalpinx

• images the uterine cavity and reveals the internal architecture of the tubal lumen • performed as out-patient basis

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

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

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)

Uterine factor of female infertility

Anatomic

abnormalities

Functional

abnormality

• Congenital

malformations

• Leiomyomas/

endometrial polyps

• Intrauterine

adhesions

•Chronic

endometritis

Basic Methods for the Evaluation of Uterine Factor

Hysterosalpingogram (HSG)

TVS or SIS

Hysteroscopy

MRI

bicornuate uterus septum myoma

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)

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)

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

Thank You!

Basic Investigation of an Infertile Couple

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