Introduction Fecundability Natural conception Epidemiologic figures Factors affecting the natural conception rate Causes of subfertility Female Subfertility Female causes of subfertility ovulation Ovarian problems Marker of ovarian reserve Tubal blockage Endometrial factors Uterine factors Cervical factors History and PE Examination Investigations Treatment Male subfertility Causes Hypothalamic-pituitary disease Obesity Primary hypogonadism Sperm transport disorders Defective ejaculation History and PE Investigations Semen analysis Pathological findings Surgical Sperm Retrieval Cryopreservation of gametes

1. Diaa Mohammad Srahin
6th year Medical Student
Al-Quds University
Obstetrics & Gynecology
December/ 2018
Hebron Governmental Hospital

2. Introduction
 A delay in conception is one of the commonest reasons
that a woman will consult her doctor.
 There is no one universal definition of Subfertility, but
the commonest accepted definition is a failure to conceive
after 12 months of regular unprotected intercourse.
 The incidence of subfertility is thought to affect about one
in seven heterosexual couples in UK.

3. Subfertility can be classified as :
 Primary, in couples who have never conceived.
 Secondary, in couples who have previously conceived.
Subfertility
Primary Secondary

4. The causes of subfertility can be
 Male causes.
 Female causes.
 Mixed.
Subfertility
Male
causes
Female
causes
Factors
affect
both sexes

5. Fecundability
This is the likelihood of conception occurring with one
cycle of appropriately timed mid-cycle intercourse.
“ likelihood of conception after 1 month of mid-cyclic
unprotected sex. “
 With the female partner age of 20 years, the fecundity
rate is 20%. By age 35 years, the rate drops to 10%.
So the fecundity changes with the female age

7. What point dose the decline become significant ???
When passed 35 years it is significant

8. Natural conception
 Eggs are thought to be fertilizable for about 12–24
hours post-ovulation, while sperm can survive in the
female reproductive tract for up to 72 hours.
 For a woman with a normal menstrual cycle of 28 days,
ovulation occurs around day 14.
 The ‘Fertile window’ for women will, therefore, be
different depending on the average length of their
menstrual cycle (e.g. for a woman with a 28-day
menstrual cycle, her optimal fertile window will be
between days 12 and 15).

9. Epidemiologic figures
 80% of couples achieve conception within 1 year.
 25% within 1st month.
 60% within 6 months.
 75% within 9 months.
 90% within 18 months.

10. Factors affecting the natural
conception rate
 Age
 Female >35 years, due to decline in oocyte quality & number.
 Male age is also an important factor; semen quality tends to fall
in men over the age of 50, while frequency of intercourse tends
to fall in men over the age of40.
 Smoking
 reduces fertility in female & semen quality in males.

11. Cont.
 Alcohol
 harmful to the fetus & can affect sperm quality .
 Coital frequency
 stress & anxiety may affect libido & coital frequency & thus
impact on fertility.
 Recommended coital frequency is two to three times per
week.
 Body weight
 Over or under weight can affect ovulation.
 women with a body mass index (BMI) of >29 or < 19 will have
difficulty conceiving.

12. Cont.
Drugs
 non-steroidal anti-inflammatory drugs (inhibit ovulation).
 chemotherapy (destroys rapidly dividing cells e.g. gametes).
 cimetidine, sulphasalazine, androgen injections (affects sperm
quality).
 Occupational hazards
 exposure to chemicals and radiation adversely affects male and
female fertility.

14. Causes of subfertility
 The main causes of subfertility will vary in different
countries.
In the UK subfertility is caused by :
A. 30% Male factors
B. 30% Female factors.
C. 25% Unexplained.
D. 15% Both Male and Female or Other Causes.

17. Female causes of subfertility
Female causes
HPO axis
dysfunction
Ovarian
factors Cervical
Endometrial
factors
Tubal

18. ovulation
 Oogenesis occurs in the ovary from the 1st trimester of embryonic
life and completed by 28-30 weeks of gestation. (7 million
oocytes).
 The oocytes are arrested at the prophase stage of the 1st meiotic
division.
 At birth, the oocyte pool reduced to 2 million.
 By menarche, 500,000 oocyte are present.
 The ovulatory process is initiated once the HPO axis matures
and FSH and LH acquire their normal secretory pattern.

20. Ovarian problems
1. Central
 Pituitary insufficiency (trauma/ tumor/ congenital)
 Hypothalamic insufficiency
 Hyperprolactinemia (drug/ tumor/ empty sella)
 Luteal phase defect
2. Peripheral defects
 Gonadal dysgenesis
 Premature ovarian failure
 Ovarian tumor
 Ovarian resistance
3. Metabolic diseases.
 PCOS ( most common cause of anovulation)
 Thyroid
 Obesity
 Androgen excess (adrenal/ neoplastic)

21. The most common cause of anovulation is PCOS.
 Women with PCOS also suffer from menstrual
irregularities (usually oligo- or amenorrhoea).
 increased hair growth (hirsutism), acne and are more
commonly overweight.
 They also are at higher risk of diabetes and cardiovascular
disorders.

22.  The diagnosis of PCOS is based on a score of two out
of three of the Rotterdam criteria

23. Marker of ovarian reserve
 In the ovary, anti-Müllerian hormone (AMH) is produced by the
granulosa cells.
 AMH levels can be measured in blood and are shown to be
proportional to the number of small antral follicles.
 In women, serum AMH levels decrease with age and are undetectable
in the post-menopausal period.
 AMH levels represent the quantity of the ovarian follicle pool and are a
useful marker of ovarian reserve.
 AMH measurement can also be useful in the prediction of the extremes
of ovarian response to gonadotrophin stimulation for in vitro
fertilization.

24. Cont.
 Female reproductive potential is directly proportionate to the
remaining number of oocytes in the ovaries, which is called ovarian
reserve.
 Ovarian reserve declines after the age of 35 in an average healthy
woman, or at an earlier age due to genetic predisposition, surgery or
following exposure to toxins, such as chemotherapy.
 The ovarian reserve can help to predict the response to ovarian
stimulation in ART.
 The AFC seen on TVUSS is a good indicator of ovarian reserve (<4
predicting low response, >16 high response).
 Neither AMH nor AFC are perfect indicators and most clinics utilize
both to assess ovarian reserve

25. Tubal blockage
 Causes:
1. previous PID such as chlamydia infection
2. Inflammatory process within the abdomen/pelvic
cavity
3. Inflammatory process as a result of surgery or
endometriosis => internal scares (adhesions).
4. History of ectopic pregnancy.

26. Endometrial factors
Any abnormality in the endometrium may prevent successful
implantation of embryo.
 Examples:
 Endometriosis (15% of infertile females have endometriosis)
 Uterine fibroids
 Adhesions.
 Polyps.
 Tubal ligation
 Can be surgically managed.

27. Uterine factors (less than 10%)
 Congenital malformations
 Submucosal fibroids
 Uterine polyps
 Asherman’s syndrome (adhesions and/or fibrosis of the
endometrium particularly but can also affect the myometrium.)

28. Cervical factors
 Cervicitis
 Cervical stenosis
 Mullerian duct abnormalities
 Inadequate mucus production

29. History and PE
Hx:
 Length of time spent trying for pregnancy.
 Any previous pregnancies.
 Coital frequency .
 Occupation.
 Menstrual history.
 Previous history of pelvic inflammatory disease .
 Previous medical and surgical history.
 Previous fertility treatment.
 Cervical smear history.
 General health – screen for history of thyroid disorders

30. Examination
 Signs of PCOS
 Thyroid disease signs
 Pelvic examination
 any uterine pathology such as fibroids
 Vaginal atrophy in POF
 Cervical stenosis & mucus
 General BP, pulse, height and weight

31. Investigations
 Check for ovarian reserve
 Check for HPO dysfunction.
 Check tubal patency:
 Hysterosalpingogram (HSG).
 Hysterocontrast synography (HyCoSy).
 Operative laparoscopy and dye test.
 HSG => radio-opaque dye => X-ray.
 HyCoSy => sono-opaque contrast =>ultrasound.

32.  Hysterosalpingogram (HSG)

33. Hysterocontrast synography (HyCoSy)

34. Treatment
 Ovulation induction(OI):
Clomifene Citrate (CC).
 Induce gonadotropin release by occupying the estrogen receptors in
the hypothalamus, thereby interfering with the normal feedback
mechanisms, increasing the release of FSH and stimulating the
ovary to produce more follicles.
 70% of women on CC will ovulate, with a pregnancy rate of 15–20%.
 There is a risk of multiple pregnancies (12%) &therefore women on CC
should be monitored by us scans to track the growth of their follicles.

35.  laparoscopic ovarian drilling (LOD)
 For unknown reasons, passing electrical energy through polycystic
ovaries can result in the induction of ovulation.
 it is a surgical procedure, & it’s only appropriate to offer such treatment
to who have not responded to CC.
 OI can also be performed by offering a small dose of FSH
to induce follicular growth.
 It require follicular tracking with US scan to minimize the risk of
multifollicular ovulation & risk of multiple pregnancy.

36.  Intrauterine insemination (IUI):
 Performed by introducing a small sample of prepared sperm into
the uterine cavity with a fine uterine catheter.
 This process usually requires mild stimulation with FSH to
produce 2-3 mature follicles.
 Follicular tracking is essential to avoid over or under stimulation.
 The success rate of this procedure ranges between 15 and 20
percent in top fertility units.

38.  In vitro fertilization (IVF):
 The success rate of IVF per cycle is about 30% in women <35 years of age.
 In essence, the ovaries are stimulated with FSH, and are encouraged to
produce up to 8–10 follicles.
 Induction of ovulation is then performed with an injection of hCG, after
which the eggs can be collected during an ultrasound guided procedure via a
very fine needle.
 These eggs will be fertilized in a petri dish with sperm or, if required, the
sperm can be injected directly into the egg (intracytoplasmic sperm
injection, ICSI).
 When fertilization occurs, the fertilized embryo(s) is then replaced into the
uterine cavity.
 Approximately 2 weeks after embryo transfer, a pregnancy test is performed to
check for successful implantation.

39.  Undergoing IVF does not preclude the patient from the normal
complications of pregnancy, such as miscarriage or ectopic
pregnancies.
 The risk of ectopic pregnancy for women who have undergone IVF is
higher than for the general population, at 3–4 per cent.
 There is the added risk of overstimulating the ovaries during an IVF
cycle.
 Patients with ovarian hyperstimulation syndrome (OHSS) present
with ascites, hugely enlarged multifollicular ovaries, pulmonary edema,
and are at risk of multiorgans failure and coagulopathy.
 These patients need to be admitted to hospital and managed under
strict protocols under the care of specialist teams.

42. • Video

43. Surgical treatment
 Offered if there is tubal blockage or endometrial
abnormality (polyp, adhesion or fibroid).

45. Causes
Hypothalamic-pituitary
disease
Obesity
Primary hypogonadism
Sperm transport
disorders
Defective
ejaculation

46.  Gonadotropin-releasing hormone (GnRH) or
gonadotropin deficiency.
 Hypogonadotropic hypogonadism
Hypothalamic-pituitary disease

47. 1. Congenital idiopathic hypogonadotropic
hypogonadism.
Isolated gonadotropin deficiency resulting in eunuchoidism.
Eunuchoidism
Sexual
infantilism
Eunuchoid
body
Undeveloped
sexual organsNo sexual
hormones
Hypothalamic-pituitary disease

48. 2. Acquired:
 Tumors: Pituitary macroadenomas e.g.
macroprolactinomas and nonfunctioning adenomas.
 Infiltrative disease: sarcoidosis, tuberculosis, fungal
infections.
 Vascular lesion: Pituitary infarction and carotid
aneurysm.
 Hormonal: hyperprolactinemia, estrogen excess,
glucocorticoid excess and androgen excess
Hypothalamic-pituitary disease

49. 3. Drugs:
 Opioid-like.
 Central nervous system-acting drugs.
 Inhibit GnRH or gonadotropin secretion, resulting in secondary
hypogonadism.
 GnRH analogues
 Suppress gonadotropin secretion, as in men with prostatic carcinoma
4. Systemic or chronic illness or chronic nutritional
deficiency.
Hypothalamic-pituitary disease

50. Obesity
 Associated with decrease in serum sex hormone binding
globulin (SHBG).
 Low serum gonadotropin, total testosterone.
 Sperm quality may also be inversely related to BMI; > 25
Kg/m2 has lower motile cells.

51. Primary hypogonadism
 Testicular disorders hypergonadotropic hypogonadism.
1) Congenital disorders:
- Klinefelter's syndrome: have very small testes and almost always have
azoospermia.
- Y chromosome related defects: microdeletions in the long arm.
Testicular biopsies in these men may show germinal cell maturation arrest
or Sertoli cell-only syndrome.
- Cryptorchidism: failure of testes descent into the scrotum.
- Defective androgen receptor or synthesis

52. Primary hypogonadism
2) Aquired disorders:
- Varicoceles : dilatations of the pampiniform plexus of the spermatic veins in
the scrotum.
Infection: viral orchitis, especially mumps.
Due to germinal cell damage, ischemia, or the immune response to the
infection.
- Drugs: alkylating agents like cyclophosphamide, antiandrogens, cimitidine.
Through inhibiting testicular androgen production or action.
- Radiation.
- Hyperthermia.
- Testicular cancer.

53. Sperm transport disorders
The epididymis is an important site for sperm
maturation.
The vas deferens transports sperm from the
epididymis to the urethra.

54. Defective ejaculation
 Spinal cord disease or trauma.
 Sympathectomy.
 Autonomic disease.
 Erectile dysfunction.
 Mechanical obstruction.
 Premature ejaculation.

55. History and PE
History:
 Length of time spent trying for pregnancy.
 Fathered any previous pregnancies.
 History of mumps or measles
 History of testicular trauma, surgery to testis
 Occupation
 Medical and surgical history

56. Physical examination:
 Testicular examination : testicular volume, consistency,
masses, absence of vas deferens, varicocele, evidence of
surgical scars.

57. Investigations
Semen analysis
 It should be performed after the patients have
abstained from sexual intercourse for 3–4 days.
 Two abnormal test results are required to diagnose
male subfertility.
normal parameters for semen analysis (WHO criteria)
Volume >1.5 ml
pH >7.2
Sperm concentration >15 million/ml
Total sperm number >39 million/ ejaculate
Motility >50% grade a & b
Morphology >30% normal forms

58. Semen analysis
The WHO reference values for semen analysis:
 Semen volume: ≥1.5 mL
 Semen pH: ≥7.2
 Sperm concentration: ≥15 million spermatozoa per mL
 Total sperm number: ≥39 million spermatozoa per
ejaculate
 Total motility : ≥40% motile or
 Progressive motility: ≥32%
 Vitality: ≥58% live spermatozoa
 Sperm morphology (percentage of normal forms): 4%

59. Pathological findings
Conditions Characteristics
Aspermia No ejaculate
Hypospermia Low ejaculate volume (< 1.5 mL)
Azoospermia No spermatozoa in the ejaculate
Cryptozoospermia < 1 million spermatozoa/mL of
ejaculate
Oligospermia < 15 million spermatozoa/mL of
ejaculate
Asthenozoospermia < 32% of spermatozoa show progressive
motility (category PR)
Teratozoospermia Increased amorphous spermatozoa
Oligoasthenoteratozoospermia (OAT
syndrome)
Low concentration, insufficient
motility, and increased amorphous
spermatozoa

62.  For men with a very low sperm count or azoospermia, it is
important to check their testosterone levels (low levels suggest a
production impairment) and LH/FSH.
 It is also important to screen for the cystic fibrosis (CF) mutation
as a congenital bilateral absence of the vas deferens (CBAVD) is a
minor variant of cystic fibrosis.
 Karyotyping is also offered as there may be Y chromosome
deletion defects.

63. Surgical Sperm Retrieval
 Where the sperm quality is low but sperm are present, ICSI is
required to help achieve a pregnancy.
 However, in the absence of naturally ejaculated sperm, patients will
have to undergo surgical sperm retrieval (SSR).
 SSR can be performed under sedation or general anesthetic.
 A fine needle is inserted into the epididymis or the testicular tissue
to obtain sperm or testicular tissue with sperm, respectively.
 The retrieved sperm can then be cryopreserved or injected into the
oocyte as part of a fresh IVF/ICSI cycle.

64. Cryopreservation of gametes
 Sperm or oocyte can be cryopreserved for later use.
 Often this process is very useful in preserving fertility for
patients undergoing chemo/radiation therapy for cancer.
 Currently, the pregnancy rate for thawed sperm/egg in top
fertility centers is very near to that of normal IVF cycles.
 This process can also be used for storage of gametes from donors
who wish to donate their sperm or eggs for altruistic reasons to
help couples with fertility problems.