Infertility, Investigation and

Management
Dr. Raedah Al-Fadhli
 Definition
• Infertility is defined as inability to conceive despite
1year of unprotected intercourse.
• It can be primary or secondary.
• Primary Infertility: no previous pregnancies
have occurred
Secondary Infertility: a prior pregnancy has
occurred
• Fertility
– Ability to conceive
• Fecundity
– Ability to carry to delivery
• Fecundability: The probability of achieving
a pregnancy within one menstrual cycle. It
is 25% in normal couples.

• Fecundity: the ability to achieve a live birth

within one menstrual cycle.
FERTILITY AND DURATION OF MARRIAGE
FOR
COUPLES WITHOUT CONTRACEPTION

• 25% of pregnancies occur within 1 month

• >60% of pregnancies occur within 6 months
• 75% of pregnancies occur within 9 months
• 80% of pregnancies occur within 12 months
• 90% of pregnancies occur within 18 months
 Emotional and Educational
Needs
• Disease of couples, not individuals
• Feelings of guilt
• Where to go for information?
• Options
• Feelings of frustration and anger
• Support group.
 Causes of infertility
• Ovulatory dysfunction (30%)
1. Hypogonadotropic anovulation.
(Hypothalamic dysfunction, extreme weight
loss, vigorous exercise and emotional
disturbance)
2. Eugonadotropic anovulation.( PCOS)
3. Hypergonadotropic anovulation. (Premature
Ovarian failure, Turner Sx, Fragile X
syndrome)
• Tubal Factor infertility.(PID)(16%)
• Male factor Infertility(30%)
• Endometriosis(4.8%)
• Unexplained (13.4%)
• Cx factors 5.2%
• Uterine factors (Fibroid, uterine
abnormalities, and adhesions)
 Overview of Evaluation
• Female
– Ovary
– Tube
– Corpus
– Cervix
– Peritoneum
• Male
– Sperm count and function
– Ejaculate characteristics, immunology
– Anatomic anomalies
The Most Important Factor in
the Evaluation of the Infertile
Couple Is:
 History taking
 Both partners should be present
 Most important part of infertility evaluation

 Fertility history: duration of infertility

 Obstetric history: number and outcome of
previous pregnancies, postpartum or
miscarriage complications
 Menstrual history: age at menarche,
regularity, duration and amount of
bleeding, abnormal bleeding.
 History taking
 Contraceptive history.
 History of medical illnesses.
 Family history of genetic diseases.
 Personal history: smoking, alcohol, drug abuse.
 Sexual history: knowledge, frequency,
dysparenuia, vaginismus.
 Gynaecological history: PID, STI.
 History suggestive of ovulatory disorders:
exercise, cyclical pelvic pains, hot flushes,
hirsutism, galactorrhoea, stress, eating
disorders, stress, eating disorders.
• Previous female pelvic surgery
• PID
• Appendicitis
• IUD use
• Ectopic pregnancy history
• DES (?relation to infertility)
• Endometriosis
 History taking in Male partner
 Sexually transmitted infections
 Testicular surgery/injury
 History of Mumps
 Radiation, cytotoxic drugs usage, exposure to
toxic substances
 Excessive heat exposure
 Drugs: cimetidine, sulphasalazine,
spironolactone, nitrofurantoin, Colchicine.
 Initial Advice
 Prescribed, over-the-counter and
recreational drug use
 Folic acid supplementation
 Susceptibility to rubella
 Cervical cancer screening
Investigation of fertility problems
and management strategies
 Physical Exam-Female
 Pelvic masses
 Uterosacral nodularity
 Abdominopelvic tenderness
 Uterine enlargement
 Uterine mobility
 Cervical abnormalities
 Thyroid exam
 Physical Exam-Male
• Size of testicles
• Testicular descent
• Varicocoele
• Outflow abnormalities (hypospadias, etc)
Ovary
 Ovarian Function
• Document ovulation:
– BBT
– Luteal phase progesterone
– LH surge
– EMBx
– U/S for Ovarian volume.
• If POF suspected, perform FSH
• TSH, PRL, adrenal functions if indicated
 Ovarian Function
• Three main types of dysfunction
– Hypogonadotrophic, hypoestrogenic (central)
– Normogonadotrophic, normoestrogenic (e.g.
PCOS)
– Hypergonadotrophic, hypoestrogenic (POF)
 BBT
• Cheap and easy, but…
– Inconsistent results
– Provides evidence after the fact.
– 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
 Luteal Phase Progesterone
• Pulsatile release, thus single level may not
be useful unless elevated
• Performed 7 days after presumptive
ovulation
• Done properly, >15 ng/ml consistent with
ovulation
 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
 Endometrial Biopsy
• Invasive, but the only reliable way to
diagnose LPD(luteal phase defect)
• Pregnancy loss rate <1%
• Perform around 2 days before expected
menstruation.
• Must be done in two different cycles to
confirm diagnosis of LPD
 ULTRASOUND
• To see the ovaries and to count the
number of primodial follicles in the
ovaries(>2mm).
• To see the ovarian volume.
Ovarian Artery
Typical triple layer endometrium
Fallopian Tubes
 Screening for Chlamydia
trachomatis
 Before uterine instrumentation
 Appropriate management
 Prophylactic antibiotics
 Tubal Function
• Evaluate tubal patency whenever there is a
history of PID, endometriosis or other
adhesiogenic condition
• Kartagener’s syndrome can be associated
with decreased tubal motility
• Tests
– HSG
– Laparoscopy
– Falloposcopy (not widely available)
 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
 Hysterosalpingography (HSG)
• Can be uncomfortable
• Pregnancy test is advisable
• Can detect intrauterine and tubal
disorders but not always definitive
NORMAL HSG
LEFT TUBAL BLOCK
HYDROSALPINX
 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
Fitz-Hugh-Curtis Syndrome
 Falloposcopy
• Hysteroscopic procedure with cannulation
of the Fallopian tubes
• Can be useful for diagnosis of intraluminal
pathology
• Promising technique but not yet
widespread
 Corpus
• Asherman Syndrome
– Diagnosis by HSG, hysteroscopy or saline ultrasound.
– Usually happen after D+C, myomectomy, other
intrauterine surgery
– Associated with hypo/amenorrhea, recurrent
miscarriage
• Fibroids, Uterine Anomalies
– Rarely associated with infertility
– Work-up:
• Ultrasound
• Hysteroscopy
• Laparoscopy
 Cervical Function
• Infection
– Ureaplasma suspected
• Stenosis
– S/P LEEP, Cryosurgery, Cone biopsy
(probably overstated)
• Immunologic Factors
– Sperm-mucus interaction
 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
– Medical options remain suboptimal
 Male Factors
• Serum T, FSH, PRL levels
• Semen analysis
• Scrotal US.
• Testicular biopsy( not an option unless combined with
cryo-preservation).
• Karyotyping.(Klinefelter SX 46XXY)
• Cystic fibrosis screen( congenital bilateral abscense of
Vas deferens).
• Antisperm antibodies.
 Male Factors-Semen Analysis
• Collected after 480 of abstinence
• Evaluated within one hour of ejaculation
• If abnormal parameters, repeat twice, 2
weeks apart
Normal Semen Analysis (WHO)

Quality
Volume
Treatment Options
 Ovarian Disorders
• Anovulation
– Clomiphene Citrate ± hCG
– Gonadotropins
– Induction + IUI (often done but unjustified)
• PRL
– Bromocriptine, Cabergoline
– TSS if macroadenoma
• POF
– ?high-dose hMG (not very effective)
 Ovarian Disorders
• Central amenorrhea
– Gonadotropins
– Pulsatile GnRH
• LPD
– Progesterone suppositories during luteal
phase
– CC ± hCG
 Ovulation Induction
• CC
– 70% induction rate, ~40% pregnancy rate
– Patients should typically be normoestrogenic
– Induce menses and start on day 2-5
– With dosages, antiestrogen effects dominate
– Multifetal rates 5-10%
– Monitor effects with ultrasound.
 Gonadotropins
• LH +FSH (also FSH alone)
• For patients with hypogonadotrophic
hypoestrogenism or normal FSH and E2
levels
• Close monitoring essential, including
estradiol levels
• Cumulative success rates of approximately
90% after 6 treatment cycles in WH0 group 1
patients, and lower for PCOS patients (40-
50%).
• 15-20 % multifetal pregnancy rate.
 Risks
CC Gonadotropins
• Vasomotor symptoms • Multiple gestation
• H/A • OHSS (~1%)
• Ovarian enlargement – Severe cases fatal if
untreated in ICU
• Multiple gestation setting
 Metformin & Ovarian Drilling

Anovulatory women with PCOS, who

have not responded to CC and with
BMI >25 should be offered Metf
combined with CC
Women with PCOS who have not
responded to CC should be offered
with Laparoscopic Ovarian Drilling
 Fallopian Tubes
• Tuboplasty
• IVF (In vitro fertilization)
 Corpus
• Asherman syndrome
– Hysteroscopic lysis of adhesions - Postop Abx,
Estrogen treatment.
• Fibroids if sumucosal
– Myomectomy(hysteroscopic, laparoscopic, open).
– Uterine artery embolization?
• Uterine anomalies
– metroplasty
 Cervix

• If cervicitis Abx

• If scant mucus low-dose estrogen

 Peritoneum (Endometriosis)
• From a fertility standpoint, excision is
better than medical management
• Lysis of adhesions
• GnRH-a (not a cure and has side effects,
expense)
• Danazol (side effects, cost)
• Continuous OCP’s (poor fertility rates)
• Chances of pregnancy highest within 6
months -1 year after treatment.
 Male Factor
• Hypogonadotrophism
– Gonadotropins
– GnRH(pulsatile)
– CC, hCG
• Varicocoele
– Ligation? (no definitive data yet)
• Retrograde ejaculation
– Ephedrine, imipramine (daily dose of 25-50mg)
– IVF with recovered sperm from the urine.
 Male Factor
• Idiopathic oligospermia
– No effective treatment
– ?IVF
– donor insemination( not an option here)