BASIC INFERTILITY WORK UP

AND INITIAL TREATMENT

DEFINITIONS:
• Infertility- when a couple has a reduced
capacity to conceive compared with the
mean capacity of the general population.
• 1 YEAR of unprotected coitus with out
conception
• Affects between 10-15% of couples.
• FECUNDABILITY- the
probability of achieving
pregnancy with in 1
menstrual cycle.
• About 25%

• FECUNDITY- ability to
achieve live birth with
one menstrual cycle.
MAJOR CHANGES IN
INFERTILITY PRACTICE:
• 1. Introduction of IVF and other ART
procedures.
• 2. Increased public awareness.
• 3. Increased proportion of women over the
age of 35
– 1/5 of U.S. women have first child after 35 y/o.
2 CATEGORIES:
• 1. Low fecundability- hypo fertile,
eventually able to conceive.
• E.g.. Oligospermia; mild endometriosis
• 2. Sterile- never able to conceive.
• Male: azospermia
• Female: complete occlusion of
oviducts.
2 FACTORS REDUCING
CONCEPTION:
• 1. Incidence of infertility increased in
increasing age of female.

• 2. Total length of time in which conception

is possible is decreased in older women.
AGING AND FERTILITY:
A. FEMALE
• 1/3 IN MID TO LATE 30’S= INFERTILITY
• ½ AFFECTED IN AGE >40.
• Increase in spontaneous pregnancy loss
– 10%= >30 yrs of age
– 18%=late 30’s
– 34%=early 40’s
– 75% rate of pre clinical and clinical pregnancy
loss = >40
– Due to impaired meiotic spindle formation in
older eggs
B. MALE
• PATERNAL AGE >40 = 20% INCREASE
IN BIRTH DEFECTS.
• DECREASE IN TESTOSTERONE
• INCREASE GONADOTROPIN
• DECREASE SPERM PRODUCTION.
CAUSES OF INFERTILITY:
FEMALE FACTOR:
• Anovulation= 10-15%
• ENDOCRINE CHANGES:
– 1. Accelerated follicular loss- in last 10-15
years before menopause.

• Begins when total # of follicle is approximately

25,000 (age 37-38)
• ↓INHIBIN and ↑ FSH- reduce quality and /or
capability of aging follicles.
• 2. SHORTER Follicular phase
– ↑FSH; Normal LH and Luteal Phase
– Cycles shortest in late 30’s , lengthen prior to
menopause.

• 3. OVARIAN FAILURE:
– ↑FSH; N Estradiol; ↓ Inhibin

• Pelvic Factors= 30-40%

– e.g.. Adhesions from endometriosis or
infection.
MALE FACTOR:
• Abnormality in male reproductive system-
30-40%
• Abnormality in the male reproductive
system= 30-40%
– Oligospermia
– increase viscosity
– low sperm motility
– low volume of semen
• Abnormal sperm –cervical mucus
penetration.
POINTS TO CONSIDER:
• Causes of infertility will not be determined in 25%
of couples.
• Optimal time in cycle for conception = day before
ovulation.
• Egg disintegrates with in a few hours after it
reaches the ampulla, then it is best that sperm be
presenting the area where egg arrives for
fertilization to occur.
• Time and timing should be emphasized.
• Couples advised to cease cigarette smoking and
drinking caffeinated beverages.
• Vaginal lubricants and chemicals may interfere
with sperm transport.
• Vaginal douching decrease chance of conception
by 30%.
ALL COUPLES:
– should do a complete history including sexual
history.
– Thorough PE
– Tests should be done to determine if female is
ovulating or with patent oviducts.
– Semen sample from male should be normal.
OVULATION DOCUMENTATION:
• should be regular monthly cycles.
• Serum progesterone level in mid luteal phase
is >10ng/ml – for adequate luteal function.
• Measurement of basal body temperature
– Shortly after awakening at least 6 -hour sleep prior
to ambulating.
– Sublingual placement of thermometer.
• Women with oligomenorrhea (interval 30 days
or longer) or amenorrhea are treated with
agents that induce ovulation irregardless if
they have occasional ovulatory cycles
SEMEN ANALYSIS:
– Abstain coitus 2-3 days before collection.
– Collect in a clean wide mouth jar after
masturbation.
– Entire specimen collected.
– Liquefaction is 15-20 minutes.
– Sperm motility declines after 2 hours.
– Specimen left warm during transport.
– if abnormality found, repeat after 2-3
occasions at least 1 month apart
• In women with Anovulation= +
hyperthyroidism or hyperprolactinemia

• Treatment:
– Thyroid hormone replacement
– Bromocriptine
LUTEAL DEFECIENCY:
• serum progesterone level below 10ng/ml
in luteal phase of several cycles.
– deficit in progesterone production.
– Never established to cause infertility.
– Diagnosed Histologically- the normal
secretory endometrial development must lag
3 days or more , behind the expected pattern
of the time of the cycle, consistent finding in 2
cycles.
IMMUNOLOGIC CAUSE OF
INFERTILITY:
• In women:
– sperm agglutinating antibody

– sperm immobilizing antibody

INFECTION:

Occult infection in the :

• A. Upper female genital tract
– -Mycoplasma hominis
– - Mycoplasma fermentans
– - C. trachomatis

• B. Male Genital Tract:

e.g.: Ureaplasma Urealyticum
ZONA-FREE HAMSTER EGG
PENETRATION TEST:

– Originally developed by Yanagimachi et al.

– Used to predict the fertilizing ability of sperm
and provides an additional more sensitive
parameters to assess sperm function than the
routine semen analysis
– Its value in the infertile couple – not
satisfactorily demonstrated.
– Expensive assay
– Should not be used as a part of infertility
diagnostic evaluation.
PROGNOSIS:
– prognosis for pregnancy is associated with
treatment of their particular cause of infertility.
– Increase probability in Anovulation as cause of
infertility.
– More chances of becoming pregnant in women
younger than 35 about 75%, than in women older
than 35% about 50%.
– Cumulative conception rate 75% in those who
tried to conceive < 3 years, and > 3 years = 30%.
LABORATORY TESTS:
Part I = Non – costly procedures.
• CBC
• Urinalysis
• FBS
• Cervical Cytology
• If women > 35 y/o a serum FSH and Estradiol
level done at Day 2,3, or 4.
• Impending ovulatory failure:
– Increase FSH levels >20 mIU/ml
– If Estradiol level > 100pg/ml
• CA -125 detect presence of endometriosis.
Other test not routine :
– TSH
– Prolactin
PART II: More costly Examinations
• 1. Hysterosalpingogram
– Fluorescence and radiographic visualization.
– Uncomfortable examination of the female
upper genital tract after instillation of
radiopaque dye following the end of menses.
– Antibiotic prophylaxis: Doxicycline 100mg BID
x 5 days, 2 days prior to procedure.
• 2. Diagnostic Laparoscopy
• - direct visualization of tubes.

• 3. Additional tests:
• - Serum FSH and prolactin in ovulatory women.
• - Luteal phase endometrial biopsy.
• - Measure of anti-sperm antibody of both male and
the female partner.
• - Bacteriologic cultures of cervical mucus and semen.
• - Hamster egg penetration test.
MANAGEMENT:
• MALE:
– General measures
– adequate sleep, diet and exercise
– Moderation in use of alcohol, and tobacco
– Relief of emotional tension.
– avoidance of regimented coitus, as long as
exposures average 2-3 times a week.
– weight reduction in obesity.
– Treatment of chronic illness or metabolic
disorder.
– avoidance of prolonged heat to scrotum.
– Urologic consultations in those with
oligospermia or azospermia.
– Varicocoele should be excluded.
– Chromosomal studies in those with
abnormality in external genitalia.
Treatment of Oligospermia:
• Triiodothyronine
• -Clomiphene Citrate
• -Human Menopausal Gonadotropin
• -HCG
• - oral androgens
• -Cortisone therapy
Treatment of FEMALE:
• OVARIAN FACTOR:
• Ovulation Defects
– nutritional deficiencies
– metabolic disorders
– chronic illness
– neurogenic disorders
– psychogenic disorders
– specific ovarian disorders
• e.g.. Ovarian tumors, PCOS, ovarian dysgenesis
• Endometriosis
– OCPs
– Danazol
– GnRH agonists
• Peri-ovarian Adhesions
– a. lysis of adhesions
– b. suspension of uterus
– c. corticosteroids
• Inadequate Luteal Phase
– General constitutional measures should not be
over-looked.
– Clomiphene Citrate = 50 mg/day for 5 days at Day 5
of cycle.
– Low dosage Estrogen from day 5 to midcycle.
– Progesterone deficiencies- give progesterone
– HCG to induce endogenous progesterone secretion.
TUBAL FACTOR:

– Peri tubal adhesions

– Fimbrial end obstruction
– middle third obstruction
– Cornual obstruction

• Operative Techniques done:

• Fimbriolysis
• Salpingolysis
• Salpingostomy
• Resection and anastomosis of midtubal obstruction
• tubal implantation for cornual obstruction.
UTERINE FACTORS:
• Leiomyoma Uteri- Myomectomy
• Retroversion- fixed, if with underlying cause of
PID, treat infection.
• Anomalies:
– uterus didelphis
– bicornuate uterus
– septate uterus- most common associated
with secondary infertility.
• Traumatic Intrauterine Synechiae-
Ashermans Syndrome
– treatment:
– gradual dilatation of cervix
– sounding or hysteroscopic visualization
during proliferative phase.
• Endometrial polyps and Hyperlasia –
direct removal during hysteroscopy.
CERVICAL FACTOR:
• Failure of sperm deposition=
Improvement of coital techniques
• Poor or hostile cervical mucus causes
are:
– endocervicitis or infections.= give antibiotics
– Inadequate estrogenic stimulation= small
doses of estrogen
– Immunologic problems= high dosage
cortisone for sperm Antibodies
• Local Cervical Pathology:
– Endocervical polyps= removed
– Cervical stenosis- gentle careful sounding
– Cervical erosions- treat infections;
electrocautery done in stages interval 4-8
weeks.
– Synechia and hypoestrenism
– Incompetent cervix- operative cerclage done
may be done at 14 weeks AOG.
INFERTILITY TESTING: AFS 1994
• 1. SEMEN ANALYSIS
• 2. HYSTEROSALPINGOGRAM
• 3. ASSESSMENT OF OVULATION
• 4. **POST COITAL TEST- not evidence based
• 5. LAPAROSCOPY- indicated cases only

• ADDED: OVARIAN RESERVE TESTING

(ASRM)
BASAL TESTING: OVARIAN
RESERVE
• 1. Day 3 FSH • <10-15mIU/ml
• 2. Estradiol • <80 pg/ml
• 3. Antral Follicle count • >3-4
– Antral volume: – VOL: > 3ml
• 4. Anti-Mullerian • >2.7
Hormone
• 5. Inhibin B • >45
CLOMIPHENE CITRATE
CHALLENGE TEST ( CCCT)
• BIO ASSAY OF FSH RESPONSE
• 100 MG/DAY DAY 5-9
• CHECK FSH DAY 3 AND DAY 10
• SUM OF >26 IU/L= POOR PROGNOSIS
• 85% OF WOWMEN WITH INCREASED
FSH= POOR STIMULATION
SCREENING
RECOMMENDATION:
• CYCLE DAY 3 FSH
• ESTRADIOL
• CCT
– REQUIRED IN :
• INFERTILE WOMEN >30 Y/O
• ANY AGE WITH UNEXPLAINED INFERTILITY
• HISTORY OF POOR RESPONSE TO
OVULATION INDUCTION.
• UTILITY IN WOMEN >40 Y/O IS UNCLEAR
– NORMAL TEST NOT REASSURING
– ABNORMAL TEST MAY BOLSTER
RECOMMENDATION OF OVUM DONATION.
IMPROVE PREGNANCY RATES:
• Cessation of smoking- depletes follicles
– Menopause 1-4 years earlier
– Inc. FSH level
– 50% decrease in implantation rate
• Keeping BMI below 25
– If more than 25, less 25% in pregnancy rate
• Metformin for PCOS
• Assessment of Ovarian reserve
• Removal of hydrosalpinges
• Removal of myomas that indent uterine cavity.
• Fertility decreases at age 40y/o.
TECHNOLOGY:
• Optimistic hope for the problem of
INFERTILITY.
• There is an increase in 2.2% in IVF
technology.
• ART- oferred in the context of marriage:
– No donor eggs
– No donor sperms
– No surrogate parenting
COMPLICATIONS:
• Ovarian Hyper stimulation
• Multiple Gestation
– Limitation of maximum of 2 embryo
transferred.
– Lessen HOM( high order multiple) pregnancy
• - ability of using frozen embryos
• New media used to be able to support
embryos day 3-5 improving implantation
rate.
• Use of ICSI= Intra-cytoplasmic sperm
injection.
Futuristic view: Menopausal women able to
conceive
– ability to auto-preserve ovum.
GOALS OF PHYSICIAN:
• SEEK AD CONSULT THE CAUSE OF
INFERTILITY
• PROVIDE ACCURATE INFORMATION.
• PROVIDE EMOTIONALSUPPORT.
• ADVISE WHEN TO STOP.