Sub-fertility
Causes &Management
Dr. Yousef Gadmour
Professor, Al-fateh university
Senior consultant, Al-Jalla Hospital
Tripoli , Libya
Definitions:
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Sub fertility- Involuntary failure to conceive
within 12 months of commencing unprotected
sexual intercourse.
Primary infertility - No previous pregnancy.
Secondary infertility- previous pregnancy.
(whatever the outcome)
Causes (and approximate incidence)
1. Idiopathic
2. Sperm defects or functional disorder
3. Ovulation failure
4. Tubal damage
5. Endometriosis
6. Coital failure
7. Cervical mucus defect
8. Obstruction of sperm ducts
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25 per cent
25 per cent
20 per cent
15 per cent
5 per cent
5 per cent
3 per cent
2 per cent
Principles of management:
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2.
3.
4.
Deal with the sub fertile couple together.
No one is at fault or to blame.
Give good explanations of causes ,
prognosis and outline of treatment of sub
fertility.
Carry out investigations and treatments
consistency in proper sequence.
History - General
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Both couples should be present.
Age.
Previous pregnancies by each partner.
Length of time without pregnancy.
Sexual history :
 Frequency
and timing of intercourse
 Use of lubricants
 Impotence, anorgasmia, dysparunia
 Contraceptive history
History - Male
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Infections; gonorrhea , tuberculosis.
Radiation, toxic exposures ,drugs.
Mumps orchitis.
Testicular injury/surgery.
occupation (Excessive heat exposure).
Smoking.
Diabetes mellitus.
History - Female
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Detailed menstrual history ; Irregular menses,
amenorrhea.
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Hirsutism.
Galactorrhoea.
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Previous pregnancies and mode of deliveries.
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Ectopic pregnancy history.
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PID.
History - Female
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Appendicitis.
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IUCD use.
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Endometriosis.
Stress.
Weight changes.
Excessive exercise.
Cervical and uterine surgery.
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Physical Examination - Male
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Weight & Height (BMI).
Size of testicles
testicles (orchidometry).
(orchidometry).
Testicular descent.
Varicocele.
Outflow abnormalities (hypospadias, etc).
General look- Klinefelter syndrome (47XXY).
Kallmann syndrome (hypothalamic hypogonadism)
(delayed puberty ,normal stature, no smell ).
Physical Examination - Female
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Weight & Height (BMI)
Hirsutism
Thyroid examination
Abdominal examination
Speculum examination - HVS, endocervical
swap
Vaginal examinationUterosacral nodularity, Uterine mobility
USS-(Vaginal)
General laboratory investigations:
Female
 FBS(GTT).
 TFT.
 chlamydial antibody titer.
 Rubella antibody titer (If negative, immunize
and advise not to try for pregnancy for 3
months).
 HIV,HBV,HCV.
General laboratory investigations:
Female
 Day 2 FSH, LH.
 Serum prolactin (fasting).
 Day 21 serum progesterone.
General laboratory investigations:
Male
 HIV,HBV,HCV.
 FBS (GTT).
 TFT.
 Serum Testosterone, FSH, PRL levels.
Routine investigation in the female
Assessment of Ovulation
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Basal body temperature
Mid luteal serum progesterone
Endometrial biopsy
Ultrasound monitoring of ovulation
BBT
Cheap and easy, but…
1. Inconsistent results.
2. Provides evidence after the fact.
3. May delay timely diagnosis and treatment;
98% of women will ovulate within 3 days of the
nadir.
4. Biphasic profiles can also be seen with LUF
syndrome.
Luteal Phase Progesterone
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Pulsatile release, thus single level may not be
useful unless elevated.
Performed 7 days after presumptive ovulation
( day 21 ).
If done properly , level >15 ng/ml consistent
with ovulation.
Endometrial Biopsy
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Invasive, but the only reliable way to diagnose luteal
phase defect (LPD).
Performed around 2 days before expected menstruation
(= day 28 by definition).
Lag of >2 days is consistent with LPD.
Must be done in two different cycles to confirm diagnosis
of LPD.
Controversy exists over the relevance of luteal phase
defect as a cause of infertility and the accuracy of the
endometrial biopsy in assessing the delay.
Postcoital test (PK tests)
Scheduled around 1-2d before ovulation
(increased estrogen effect)
 48hours of male abstinence before test
 No lubricants
 Evaluate 8-12h after coitus
(overnight is ok!)
 Remove mucus from cervix
(forceps, syringe)
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Postcoital test (PK test)
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PK (normal values in yellow)
Quantity (very subjective)
 Quality (spinnbarkeit) (>8 cm)
 Clarity (clear)
 Ferning (branched)
 Viscosity (thin)
 WBC’s (~0)
 progressively motile sperm/hpf (5-10/hpf)
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Problems with the PK test
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Subjective.
Timing varies; may need to be repeated.
In some studies, “infertile” couples with an
abnormal PK conceived successfully during that
same cycle.
Tubal Function
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Evaluate tubal patency whenever there is a
history of PID, endometriosis or other
adhesiogenic condition.
Tests:
HSG
 Laparoscopy
 Falloposcopy (not widely available)
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Hysterosalpingography (HSG)
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Can be uncomfortable.
Done at the end of menses.
Can detect intrauterine and tubal disorders but
not always definitive.
Laparoscopy
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Invasive; requires OT or office setting.
Can offer diagnosis and treatment in one sitting.
Not necessary in all patients.
Uses (examples):
1. Lysis of adhesions
2. Diagnosis and excision of endometriosis
3. Myomectomy
4. Tubal reconstructive surgery
5. Test of tubal patency by dye test
Falloposcopy
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Hysteroscopic procedure with cannulation
of the Fallopian tubes.
Can be useful for diagnosis of intraluminal
pathology.
Promising technique but not yet widespread.
Assessment of uterine cavity
Hysteroscopy
 It is advisable to assess the uterine cavity
pathology as submucous fibroid, polyps,
uterine malformation, and others .
 Outpatient hysteroscopy,
hysterosalpingography are equivalent
regarding evaluation of uterine cavity
pathology
Routine investigation in the male
Semen analysis
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Test after (~3) days abstinence from intercourse.
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If abnormal parameters, repeat twice, 2 weeks apart
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Normal values:
Volume: 2 to 6 ml
Density: 20 to 250 million /ml
Motility: > 50 % with forward motion within 2 hours
Morphology: > 50 % normal sperm
Other Male Investigation
Doppler USS (varicocele).
 Testicular Biopsy.
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Treatment Options
Ovarian Disorders
Anovulation
Clomiphene Citrate (CC) ± hCG
 Human Menopausal Gonadotropin (hMG)
 Pure FSH
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Central amenorrhea
CC first, then hMG
 Pulsatile GnRH
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Ovarian Disorders
Hyperprolactinaemia:
 Drugs :Bromocriptin, Carbegoline(Dostinex),
Quinagolide (Norprolac)
 Surgery if macroadenoma
Premature ovarian failure :
 ? high-dose hMG (not very effective)
Luteal phase defect:
Progesterone suppositories during luteal phase
 CC ± hCG
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Ovulation Induction
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Clomiphene Citrate
 Compete with natural oestrogens by blocking
receptors in target organs including the
pituitary, leading to increased FHS levels.
 70% induction rate, ~40% pregnancy rate.
 Patients should typically be normoestrogenic.
 Induce menses and start on day 2 for 5 days.
 With high dosages, antiestrogen effect
dominate.
 Multiple pregnancy rates 5-10%.
 Monitor effects with USS & D21 progesterone.
hMG
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LH +FSH (also FSH alone = Metrodin)
For patients with hypogonadotrophic
hypoestrogenism or normal FSH and E2 levels
Close monitoring essential, including estradiol
levels & USS
60-80% pregnancy rates overall, lower for
PCOS patients
10-15% multiple pregnancy rate
Risks
CC
 Vasomotor symptoms
 Ovarian enlargement
 Multiple gestation
 NO risk of
malformations
hMG
 Multiple gestation
 OHSS (~1%)
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Can often be managed
as outpatient
Diuresis
Severe cases fatal if
untreated in ICU
setting
Fallopian Tubes
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Tuboplasty
IVF
Corpus
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Asherman syndrome
Hysteroscopic Lysis of adhesions (scissor)
 Postop. ; IUCD, E2
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Fibroids (rarely need treatment)
Myomectomy ( hysteroscopic, laparoscopic, open)
 ??Uterine artery embolization.
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Uterine anomalies (rarely need treatment)
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Metroplasty.
Peritoneum (Endometriosis)
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From a fertility standpoint, excision beats medical
management (Laser therapy ).
Lysis of adhesions.
GnRH-a (Not a cure and has side effects & expensive).
Danazol (side effects, cost).
Continuous OCP’s ( poor fertility rates ).
Chances of pregnancy highest within 6 -12 months after
treatment.
Male Factor
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Hypogonadotrophism
hMG
 GnRH
 CC, hCG ( results poor )
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Varicocoele
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Ligation? ( No definitive data yet )
Retrograde ejaculation
Ephedrine, imipramine
 AIH with recovered sperm
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Male Factor
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Idiopathic oligospermia
No effective medical treatment
 IVF (in-vitro fertilization)
 ICSI ( Intra- cytoplasmic sperm injection )
 TESE( Testicular Sperm Extraction )
 MESA(Microsurgical Epididymal Sperm Aspiration)
 ?? donor insemination
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Unexplained Infertility
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15-20% of couples
Consider PRL, laparoscopy, other hormonal tests,
cultures, Antisperm Abs. testing, sperm penetration
assay if not done.
Review previous tests for validity.
Empirical treatment:
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Ovulation induction
IUI
Consider IVF and its variants
Adoption
Summary
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Sub fertility is a common problem.
Sub fertility is a disease of couples.
Evaluation must be thorough, but individualized.
Treatment is available, including IVF, but can be
expensive, invasive, and of limited efficacy in
some cases.
Consultation with a reproductive endocrinologist
is advisable.
Thanks