1. Sub-fertility Causes &Management
Dr. Yousef Gadmour Professor, Al-fateh university
Senior consultant, Al-Jalla Hospital
Tripoli , Libya

2. 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)

3. Causes (and approximate incidence)
1. Idiopathic per cent
2. Sperm defects or functional disorder - 25 per cent
3. Ovulation failure per cent
4. Tubal damage per cent
5. Endometriosis per cent
6. Coital failure per cent
7. Cervical mucus defect per cent
8. Obstruction of sperm ducts per cent

4. Principles of management:
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.

5. History - General Frequency and timing of intercourse
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

6. History - Male Infections; gonorrhea , tuberculosis.
Radiation, toxic exposures ,drugs.
Mumps orchitis.
Testicular injury/surgery.
occupation (Excessive heat exposure).
Smoking.
Diabetes mellitus.

7. History - Female
Detailed menstrual history ; Irregular menses, amenorrhea.
Hirsutism.
Galactorrhoea.
Previous pregnancies and mode of deliveries.
Ectopic pregnancy history.
PID.

8. History - Female Appendicitis. IUCD use. Endometriosis. Stress.
Weight changes.
Excessive exercise.
Cervical and uterine surgery.

9. Physical Examination - Male
Weight & Height (BMI).
Size of testicles (orchidometry).
Testicular descent.
Varicocele.
Outflow abnormalities (hypospadias, etc).
General look- Klinefelter syndrome (47XXY).
Kallmann syndrome (hypothalamic hypogonadism) (delayed puberty ,normal stature, no smell ).
Weight & Height (BMI).
Size of testicles (orchidometry).
Testicular descent.
Varicocele.
Outflow abnormalities (hypospadias, etc).
General look- Klinefelter syndrome (47XXY).

10. Physical Examination - Female
Weight & Height (BMI)
Hirsutism
Thyroid examination
Abdominal examination
Speculum examination - HVS, endocervical swap
Vaginal examination Uterosacral nodularity, Uterine mobility
USS-(Vaginal)

11. 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.

12. General laboratory investigations:
Female
Day 2 FSH, LH.
Serum prolactin (fasting).
Day 21 serum progesterone.

13. General laboratory investigations:
Male
HIV,HBV,HCV.
FBS (GTT).
TFT.
Serum Testosterone, FSH, PRL levels.

14. Routine investigation in the female
Assessment of Ovulation
Basal body temperature
Mid luteal serum progesterone
Endometrial biopsy
Ultrasound monitoring of ovulation

15. 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.

16. 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.

17. 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.

18. 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)

19. 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)

20. 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.

21. Tubal Function
Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition.
Tests:
HSG
Laparoscopy
Falloposcopy (not widely available)

22. Hysterosalpingography (HSG)
Can be uncomfortable.
Done at the end of menses.
Can detect intrauterine and tubal disorders but not always definitive.

23. Laparoscopy Invasive; requires OT 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
Test of tubal patency by dye test

24. Falloposcopy
Hysteroscopic procedure with cannulation of the Fallopian tubes.
Can be useful for diagnosis of intraluminal pathology.
Promising technique but not yet widespread.

25. 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

26. 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

27. Other Male Investigation
Doppler USS (varicocele).
Testicular Biopsy.

28. Treatment Options

29. Ovarian Disorders Anovulation Central amenorrhea
Clomiphene Citrate (CC) ± hCG
Human Menopausal Gonadotropin (hMG)
Pure FSH
Central amenorrhea
CC first, then hMG
Pulsatile GnRH

30. 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

31. 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.

32. 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

33. 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

34. Fallopian Tubes
Tuboplasty
IVF

35. Corpus Asherman syndrome Fibroids (rarely need treatment)
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.

36. 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 months after treatment.

37. Male Factor Hypogonadotrophism Varicocoele Retrograde ejaculation hMG
GnRH
CC, hCG ( results poor )
Varicocoele
Ligation? ( No definitive data yet )
Retrograde ejaculation
Ephedrine, imipramine
AIH with recovered sperm

38. 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

39. 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

40. 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.

41. Thanks