About infertility

1. INFERTILITY
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2. INFERTILITY
• Is the inability to achieve conception despite one
year of frequent unprotected intercourse.
• Synonymous with sub fertility.
• Infertility can be:
 Primary Infertility:
- Applies to those who have never conceived.
 Secondary Infertility:
- Designates those who have conceived at some time
in the past. 2

3. FECUNDABILITY:
• Is the probability of achieving pregnancy with in a single
menstrual cycle.
• Of a normal couple is 20-25%.
• On the basis of this estimate, about 90% of couples should
conceive after 12 months of unprotected intercourse.
FECUNDITY:
• Is the probability of achieving a live birth with in a single
cycle.
STERILITY:
• Implies an intrinsic inability to achieve pregnancy, whereas
infertility implies a decrease in the ability to conceive.
• Affects 1-2% of couples.
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4. CAUSES OF INFERTILITY
• Male Factor = 25 – 40%
• Female Factor = 40 – 55%
• Both = 10%
• Unexplained = 10%
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5. Female Infertility
Causes of infertility in the female
• Ovulatory dysfunction = 30 – 40%
• Tubal or peritoneal factor = 30 – 40%
• Unexplained infertility =10 – 15%
• Miscellaneous causes =10 –15%
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6. Causes of female infertility...
Ovulatory dysfunction / Factor
1. Central defects
• Chronic hyperandrogenemic anovulation
• Hyperprolactinemia (drug, tumor, empty selia)
• Hypothalamic insufficiency
• Pituitary insufficiency (trauma, tumor, congenital)
2. Peripheral defects
• Gonadal dysgenesis
• Premature ovarian failure
• Ovarian tumor
• Ovarian resistance 6

7. Causes of female infertility...
Ovulatory dysfunction / Factor...
• Metabolic disease
- Thyroid disease
- Liver disease
- Renal disease
- Obesity
- Androgen excess, adrenal or neoplastic
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8. Causes of female infertility...
Pelvic Factor ( Tubo-peritoneal factors)
• Infection
- Appendicitis
- Pelvic inflammatory disease
- Uterine adhesions (Asherman's syndrome)
• Endometriosis
• Structural abnormalities
- Diethylstilbestrol (DES) exposure
- Failure of normal fusion of the reproductive
tract
- Myoma 8

9. Causes of female infertility...
Pelvic Factor ( Tubo-peritoneal factors)...
Cervical Factor
• Congenital
- DES exposure
- Müllerian duct abnormality
• Acquired
- Surgical treatment
- Infection
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10. Medical History for Female Factor Infertility
• In utero diethylstilbestrol (DES) exposure
• History of pubertal development
• Present menstrual cycle characteristics (length, duration,
molimina)
• Contraceptive history
• Prior pregnancies, outcomes
• Previous surgeries, especially pelvic
• Prior infection
• History of abnormal Papanicolaou (Pap) smear, treatment
• Drugs and medications
• General health (diet, weight stability, exercise patterns,
review of systems)
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11. Evaluation of Female Factors
Ovulatory Factor
• Review of historical factors including:
- The onset of menarche
- Present cycle length (intermenstrual interval)
- Presence or absence of premenstrual symptoms (molimina),
such as breast tenderness, bloating, or dysmenorrhea.
- Signs and symptoms of systemic disease, particularly of
hyperthyroidism or hypothyroidism
- Physical signs of endocrine disease (ie, hirsutism,
galactorrhea, and obesity)
- The degree and intensity of exercise
- History of weight loss, and
- Complaints of hot flushes
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12. Evaluation of Female Factors...
Ovulatory Factors
Follicular Pool:
• A female will have the highest number of germ cells, ≈ 6
million, in her ovaries at 20 weeks of GA.
• Only 1–2 million oocytes remaining at the time of birth.
• The ovaries contain ≈ 500,000 oocytes at the time of first
ovulation.
• Menopause signals the complete depletion of germ cells,
with a woman having ovulated about 500 oocytes during her
reproductive years.
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13. Evaluation of Female Factors...
Ovarian Reserve
• An inverse relationship exists between fecundity & the age of the woman.
• Ovarian reserve should be evaluated in women > 35 years of age who are
seeking fertility
• Evaluation of the level of FSH and estradiol in the early follicular phase
(cycle days 2–4) may provide helpful guidance in terms of the likelihood
of achieving success
Female Aging and Infertility
Female Age (years) Infertility
20–29 8.0%
30–34 14.6%
35–39 21.9%
40–44 28.7%
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14. Evaluation of Female Factors...
Confirmation of Ovulation
• History of mittelschmerz &/or regular menses with molimina
(headaches, bloating, cramping, and emotional lability) and
mild dysmenorrhea occur at intervals of 28–32 days, the
likelihood of the patient having regular ovulatory cycles is
very high.
• Perform a serum progesterone assay in the mid-luteal phase,
or the third week of the cycle.
• Progesterone level of > 3 ng/mL is consistent with ovulation.
• Pelvic Ultrasonography
• Urinary LH kits or serum LH assay.
- Ovulation occurs 24–36 hours after the onset of the LH surge
and 10–12 hours after the peak of the LH surge.
- The kits can be used to time intercourse or intrauterine
insemination. 14

15. Evaluation of Female Factors...
Confirmation of Ovulation...
• Basal body temperature (BBT):
- Progesterone has a central thermogenic effect; it elevates the
BBT by an average of 0.8 °F during the luteal phase.
• Endometrial biopsy:
- Is performed 2–3 days before the expected onset of menses
- The finding of secretory endometrium confirms ovulation
• Cervical mucous
- Within 48 hours of ovulation, the cervical mucus changes
under the influence of progesterone to become thick, tacky,
and cellular, with loss of the crystalline fernlike pattern on
drying.
• The only absolute documentation of release of an oocyte is
pregnancy 15

16. Evaluation of Female Factors...
• In the case of oligomenorrhea, amenorrhea, short
or very irregular menstrual cycles, or when
ovulation is not confirmed, evaluation of the
hypothalamic-pituitary-ovarian axis is warranted.
• A usual initial assessment includes the serum
concentrations of:
- FSH,
- estradiol,
- prolactin, and
- thyroid-stimulating hormone. 16

17. Infertility Testing
Etiology Evaluation
Ovulatory dysfunction Serum midluteal progesterone
Ovulation predictor kit
Early follicular FSH ± estradiol level (ovarian reserve)
± Serum measurements (TSH, prolactin, androgens)
± Ovarian sonography (antral follicle count)
± Basal body temperature chart
± Endometrial biopsy (luteal phase defect)
Tubal/pelvic disease Hysterosalpingography
Laparoscopy with chromotubation
Uterine factors Hysterosalpingiography
Transvaginal sonography
Saline-infusion sonography
Magnetic resonance imaging
Hysteroscopy
Laparoscopy
Cervical factor ± Postcoital test
Male factor Semen analysis
FSH = follicle-stimulating hormone; TSH = thyroid-stimulating hormone. 17

18. Normal Hysterosalpingiography
(HSG)
18

19. HSG of Asherman’s Syndrome
(a "moth-eaten" appearance)
19

20. HSG showing Bilateral
hydrosalpinges (tubal blockage &
dilatation)
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21. Treatment of female factor infertility
• Ovulatory factors:
- Induction of ovulation can be accomplished in 90–95% of
patients with chronic anovulation, normal ovarian reserve,
and absence of other endocrine abnormalities (eg,
hyperprolactinemia or hypothyroidism).
- Ovulation induction with:
 Clomiphene citrate
 Gonadotropins, often used in conjunction with IUI
1. Human Menopausal Gonadotropin (hMG)
- contains LH & FSH, given IM
2. recombinant FSH (rFSH)
- contains purely FSH, given SC
3. human chorionic Gonadotropin (hCG)
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22. Treatment of female factor infertility
...
• If pregnancy is not achieved with ovulation induction, IVF-
ET is the next modality in the treatment algorithm
• Modification of lifestyle or body habitus does not
successfully restore ovulation in the patient diagnosed with
hypothalamic insufficiency, pulsatile GnRH is another viable
option with high likelihood of restoring normal ovulation.
• Treatment of Hypothyroidism and hyperprolactinemia
Treatment of Pelvic Factors:
• Laparoscopic resection or ablation
- To release adhesions in Endometriosis
• Laparoscopic or open Tuboplasty in tubal blockage
• Myomectomy for myoma
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23. Treatment of female factor
infertility... ...
• Treatment of Pelvic Factors:
The Cervical Factor
• Cervicitis and inflammatory changes:
=> treatment of patient and partner with Doxycycline.
• The absence of nurturing mucus at midcycle:
=> treated by bypassing the mucus with intrauterine insemination.
• When the cervix is altered by congenital malformation or past surgical
treatment:
=> intrauterine insemination with washed sperm can be anticipated to
result in pregnancy in 20–30% of patients per cycle in each of the first 3
cycles of treatment.
• Cervical factor patients who do not respond to these therapies can be
offered: - IVF,
- Gamete intrafallopian transfer (GIFT), or
- Zygote intrafallopian transfer (ZIFT),
although GIFT and ZIFT are now rarely used.
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24. Treatment of female factor
infertility...
Unexplained Infertility
• A diagnosis of unexplained infertility is assigned to couples
with normal results of a standard infertility work-up.
• The main treatment options include:
- Expectant observation with timed intercourse,
- Ovarian stimulation with or without IUI, and IVF.
- Studies support the use of clomiphene with IUI for up to 4
cycles.
- The next step is usually hMG with IUI for 3 cycles; if
unsuccessful, IVF should be considered.
• Adoption is also an option !
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25. Male Infertility
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26. Causes of male infertility
• Hypothalamic pituitary disease
(Secondary Hypogonadism) 1-2%
• Testicular disease
(Primary Hypogonadism) 30-40%
• Post testicular defects
(Disorders of sperm transport) 10-20%
• Non-classifiable 40-50%
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27. Causes of Male Infertility…
1. Hypothalamic – pituitary disorders (GnRH; LH
and FSH deficiency):
= > Secondary hypogonadism
A. Congenital disorders
- Congenital GnRH deficiency
(Kallmann’s syndrome)
- Hemochromatosis
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28. Causes of Male Infertility…
B. Acquired disorders
- Pituitary and hypothalamic tumors
(macroadenoma, craniopharyngioma)
- Trauma, post surgery, post irradiation
- Vascular (infarction, aneurysm)
- Hormonal (hyperprolactinemia, excess of androgen,
estrogen, and cortisol levels)
- Drugs (opioids, psychotropic drugs, GnRH
agonists or antagonists)
C. Systemic disorders
- Chronic illnesses
- Nutritional deficiency
- Obesity
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29. Causes of Male Infertility…
2. Primary gonadal disorders
A. Congenital
- Klinefelter’s syndrome (47 XXY)
- Cryptorchidism
- Myotonic dystrophy
- Varicocele
- Androgen insensitivity syndrome
- 5-alpha-reductase deficiency
- Y- chromosome deletions
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30. Causes of Male Infertility…
• Acquired disorders
- Orchitis (viral, granulomatous, bacterial)
- Drugs (alkylating agents, alcohol, marijuana,
ketoconazole, spironolactone)
- Ionizing radiation
- Environmental toxins (Pb, Hg, carbon disulfide)
- Hyperthermia
- Immunologic disorders
- Trauma, torsion, castration
- Systemic illnesses (renal failure, cirrhosis, cancer)
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31. Causes of Male Infertility…
3. Disorders of sperm transport
- Epididymal dysfunction (drugs, infection)
- Abnormalities of the vas deferens
(congenital absence, infection, vasectomy)
- Ejaculatory dysfunction
(premature ejaculation, autoimmune dysfunction)
4. Unexplained male factor infertility
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32. Anatomy of male reproductive organ
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33. EVALUATION OF MALE INFERTILITY
• History
• Physical exam
• Investigations
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34. History
• Focusing on potential causes of infertility
• HX of – chronic medical illnesses : - DM
- TB
- Bronchiectasis
- Chronic bronchitis
- Sinusitis
- Renal failure
- Hepatic failure
- Infections like: - mumps orchitis
- STD
- GUT infections
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35. History Continued…
• Surgical procedures involving inguinal and scrotal
areas such as :
- Prostatectomy
- Vasectomy
- Orchidectomy
- Hypospadias
- Repair of urethral stricture
- Varicocele
- Hydrocele
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36. History Continued…
• Developmental history
- Testicular descent
- Pubertal development
- Loss of body hair
• Drugs & Environmental exposures
- Alcohol, smoking
- Radiation therapy
- Anabolic steroids
- Cytotoxic chemotherapy
- Pesticide exposure
- Drugs causing hyperprolactinemia
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37. History Continued…
• Sexual history
- Libido
- Frequency of intercourse
- Previous fertility
• School performance
E.g. learning disabilities in case of Klinefelter's syndrome.
• High grade fever >38°c with in the past 6 months.
• Testicular injury, torsion
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38. Physical Exam Findings…
• P/E: - Focuses on evidence of androgen deficiency
• GA: - Eunchoidal proportions
- Arm span>2cm than height.
- Heel to pubis >2cm than pubis to crown
- Increased body fat
- Decreased muscle mass
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39. Physical exam Continued…
• SKIN:
- Loss of pubic, axillary’s & facial hair
- Decreased oiliness of skin
- Fine facial wrinkling suggests long standing
androgen deficiency.
• BREASTS:
– Gynecomastia  decreased androgen to
estrogen ratio.
• EXTERNAL GENITALIA
- Penis  - Hypospadias
- Surgical or traumatic scars
- Ulceration
- Urethral discharge 39

40. Physical exam continued…
• Testis:
 Site of testis:
- High in scrotum
- Inguinal
- Ectopic
- Impalpable which may be intra-abdominal
or absent
 Position & Axis
 Testicular Volume
 Consistency
• Epididymes: - Palpable?
- Consistency:
- Cystic / Indurated / Nodular
- Tender? 40

41. Physical exam continued…
• Vas deferens: - Should be palpated
- Congenitally absent?
• Scrotal swelling: - Varicocele?
- Hydrocele?
- Hernia?
- Orchitis?
- Testicular tumors?
- Torsion?
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42. Physical exam continued…
• Prostate: - PR
• Seminal Vesicles:
- Normally not palpable
- Obstructive Azoospermia has cystic
deformities.
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43. Investigations
1. SEMEN ANALYSIS
• A STANDARD SEMEN ANALYSIS
– Measurement of semen volume & PH
– Microscopy of debris & agglutination
– Sperm concentration, motility , and morphology
– Sperm leukocyte count
– Search for immature germ cells.
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44. Objective criteria for Dx
• Normal semen
1. Spermatozoa:
- concentration ≥ 20 million /ml
- motility ≥ 50%
- morphology ≥ 30% normal head
- MAR/ IB ≤ 10% of motile sperms are antibody coated
& no agglutinations
2. Seminal plasma:
- Volume ≥ 2ml
- PH b/n 7.2 and 7.8 inclusive
- WBC < 1million
- Culture < 1000 bacteria /ml
- Biochemistry = normal
- Appearance & consistency = normal
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45. Semen analysis…
• Teratozoospermia
- morphology < 30% normal head
• Asthenozoospermia
- motility < 25% grade A motility
• Oligozoospermia
- Concentration < 20 million /ml
• Azoospermia
- concentration = 0.0 million /ml
- seminal plasma volume > 0.0ml
• Aspermia
- seminal plasma volume = 0.0ml
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46. Semen Analysis…
• SPECIALIZED SEMEN ANALYSIS
– Sperm auto antibodies
– Semen biochemistry
– Semen culture
– Sperm- Cervical mucus interaction
– Sperm function tests
- Computer-aided sperm analysis
- Acrosome reaction
- Zona-free hamster oocyte penetration test
- Human Zona pellucida binding test
– Sperm chromatin and DNA assays
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47. Investigations…
2 . GENETIC TESTS
- sex chromosome mutation test
- somatic mutation test
- androgen receptor
3. ENDOCRINE TESTS :
- serum: - Testosterone
- LH
- FSH
- Prolactin
- TSH
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48. Investigations…
4. OTHER INVESTIGATIONS
- CBC - ESR
- LFT - RFT
- FBS - VDRL
- U/A
- Prostatic Expression fluid
- Post massage urine
- Post orgasm urine
- Scrotal thermography
- Doppler U/S
- Imaging of Hypothalamo-Pituitary area
- Testicular Biopsy
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49. …
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50. …
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51. TREATMENT OF MALE INFERTILITY
• General considerations
-Concurrent male & female infertility
• Use of ART
- improved the outlook for many couples
- complex, invasive, expensive & often unsuccessful
• Limited Available Treatment
- for irreversible infertility
- improves sexual function, mood, bone & muscle
mass
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52. TREATMENT OF MALE INFERTILITY…
 Specific Treatment Available
1. Hypogonadotropic Hypogonadism due to
hyperprolactinemia
- Dopamine agonists for lactotroph macroadenoma
- D/C drugs causing hyperprolactinemia
- Gonadotropin Rx if serum Testosterone doesn’t
increase within 6 months of correction of serum
prolactin level
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53. TREATMENT OF MALE INFERTILITY…
2. Hypogonadotropic Hypogonadism due to
other causes
- Due to hypothalamic or pituitary diseases:
=> Rx with Gonadotropins
i.e., hCG 1500-2000IU 3x/week IM/SC for
at least 6 months
- Due to hypothalamic disease
=> Rx with GnRH
53

54. TREATMENT OF MALE INFERTILITY…
• Treatment of Uncertain Efficacy
- Inconclusive evidence for their efficacy:
- Genital Infections
=> treat infection
- Sperm Autoimmunity
=> high dose glucocorticoids
- Retrograde Ejaculation
=> IUI
- Varicocele
=> high ligation or embolization of spermatic veins
- Obstructive Azoospermia
=> microsurgical end to end anastomoses or
sperm aspiration & in vitro fertilization
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55. TREATMENT OF MALE INFERTILITY…
• Empirical Therapy
- clomiphene , hormones, vitamines, cooling of testis
• Assisted Reproductive Techniques (ART)
- Intrauterine Insemination (IUI)
- In Vitro Fertilization (IVF)
- Intracytoplasmic sperm injection (ICSI)
- Artificial insemination with donor semen (AI)
• Potential Treatments in the future
- Germ cell transplantation
• Adoption is also an option !
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56. References
• Current Diagnosis & treatment in Obstetrics &
Gynecology, 10th edition, 2006
• Novak’s Gynecology, 14th edition, 2007
• WHO manual for the standard investigation and
diagnosis of the infertile couple, 1993
• Clinical Gynecologic Endocrinology & Infertility, Leon
Speroff, 7th edition, 2005
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