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Sub-fertility
Causes &Management
Dr. Yousef Gadmour
Professor, Al-fateh university
Senior consultant, Al-Jalla Hospital
Tripoli , Libya
Definitions:
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
-
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:
1.
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
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
Infections; gonorrhea , tuberculosis.
Radiation, toxic exposures ,drugs.
Mumps orchitis.
Testicular injury/surgery.
occupation (Excessive heat exposure).
Smoking.
Diabetes mellitus.
History - Female
Detailed menstrual history ; Irregular menses,
amenorrhea.
Hirsutism.
Galactorrhoea.
Previous pregnancies and mode of deliveries.
Ectopic pregnancy history.
PID.
History - Female
Appendicitis.
IUCD use.
Endometriosis.
Stress.
Weight changes.
Excessive exercise.
Cervical and uterine surgery.
Physical Examination - Male
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
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
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
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
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)
Postcoital test (PK test)
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)
Problems with the PK test
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
Evaluate tubal patency whenever there is a
history of PID, endometriosis or other
adhesiogenic condition.
Tests:
HSG
Laparoscopy
Falloposcopy (not widely available)
Hysterosalpingography (HSG)
Can be uncomfortable.
Done at the end of menses.
Can detect intrauterine and tubal disorders but
not always definitive.
Laparoscopy
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
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
Test after (~3) days abstinence from intercourse.
If abnormal parameters, repeat twice, 2 weeks apart
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.
Treatment Options
Ovarian Disorders
Anovulation
Clomiphene Citrate (CC) ± hCG
Human Menopausal Gonadotropin (hMG)
Pure FSH
Central amenorrhea
CC first, then hMG
Pulsatile GnRH
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
Ovulation Induction
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
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%)
Can often be managed
as outpatient
Diuresis
Severe cases fatal if
untreated in ICU
setting
Fallopian Tubes
Tuboplasty
IVF
Corpus
Asherman syndrome
Hysteroscopic Lysis of adhesions (scissor)
Postop. ; IUCD, E2
Fibroids (rarely need treatment)
Myomectomy ( hysteroscopic, laparoscopic, open)
??Uterine artery embolization.
Uterine anomalies (rarely need treatment)
Metroplasty.
Peritoneum (Endometriosis)
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
Hypogonadotrophism
hMG
GnRH
CC, hCG ( results poor )
Varicocoele
Ligation? ( No definitive data yet )
Retrograde ejaculation
Ephedrine, imipramine
AIH with recovered sperm
Male Factor
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
Unexplained Infertility
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:
Ovulation induction
IUI
Consider IVF and its variants
Adoption
Summary
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