This document discusses a case of a 33-year-old nulliparous and obese woman presenting with infertility after 5 years of marriage. It defines infertility, discusses its etiologies including tubal disease, endovascular factors, and unexplained infertility. It also discusses lifestyle advice for improving fertility in males and females. The document then discusses polycystic ovarian syndrome (PCOS), describing its pathophysiology, diagnostic criteria using Rotterdam criteria, and clinical and biochemical signs of hyperandrogenism. It also discusses scenarios involving male factor infertility and use of ovarian stimulation and IVF.

1. CLINICO-
PATHOLOGICAL
CORRELATION

2. MOHD
HANAFI
SURYA
SUPERVISOR: RAJ
DR. TAN NUGROHO MICHAEL
CIPTO RIYANTO WONG
ANGEL
KWAN
NUR
AINURA
CPC FATIN
AKMAL

3. HISTORY
• 33 | nullipara | obese
• Fertility | after 5 years marriage
• Menarche: 13 (regular)
• Currently: Irregular menses | Weight gain
• Day 2: FSH 3.5 mIU/ml | LH 5 mIU/ml

4. DEFINITION: INFERTILITY
Infertility
is defined as Primary happened
failure to Infertility in woman
conceive who has
after one never
year of conceived
unprotected
coitus at Secondary happened
frequent Infertility in a woman
intervals. who has
conceived
before

5. AETIOLOGY: INFERTILITY
Coital
problems, 5
Endometriosis, Fi Unexplained
broid, 9 infertility, 28
Tubal
diseases, 14
Ovulatory Male factor, 21
disorder, 18

6. MALE: INFERTILITY ADVICES
– 2nd most common cause
– BMI > 29 may reduced fertility.
– increased scrotal temperature.
– excessive alcohol consumption
(NICE,2004).
– smoker’s sperm concentration is
on average 13-17% lower than
non-smokers. (Jenkins et. al 2003)

7. FEMALE: INFERTILITY ADVICES
– declines with age.
(NICE, 2004)
– Moderate weight loss (Health
Education Authority, 1996).
– limit their alcohol intake
(Jensen et al 1998).
– stop smoking (RCOG, 1998).
– Genital tract infection
(Winter and Ahmad, 1998)

8. 1
COMMENT THE
ULTRASOUND
FINDINGS?

10. WHAT IS THE SUGGESTIVE
AND HOW TO DIAGNOSE
2

11. POLYCYSTIC
OVARIAN SYNDROME

12. WHAT IS PCOS
• Is a heterogenous disorder
affecting the
reproductive, endocrine and
metabolic systems.
• PCOS is often complicated by
chronic anovulatory infertility
and hyperandrogenism with the
clinical manifestation of
oligomenorrhoea, hirsutism
and acne

13. PATHOPHYSIOLOGY: PCOS
Genetically have insulin receptor disorder
and thus insulin resistance-
HYPERINSULINAEMIA
During puberty- GH spurt- IGF1 ↑↑
Hyperinsulinaemia+IGF1 cause ovarian
hyperstimulation
Ovarian hyperstimulation- cause thecal cell
hyperplasia and excessive androgen
production

14. PATHOPHYSIOLOGY: PCOS
HYPERINSULINAEMIA- also act on liver to reduce
sex hormone binding globulin (SHBG)- increase
free testosterone
Increased LH production by anterior pituitary relative
to FSH. Cause theca cell stimulation. Cyst formation
Follicles do not mature due to premature surge
in LH. Decreased FSH:LH cause inability of ovary
to convert androgen to estrogen.

15. HOW TO DIAGNOSE: PCOS
• Rotterdam criteria for diagnosis
• The diagnosis of PCOS requires the
exclusion of all other disorders that can
result in menstrual irregularity and
hyperandrogenism:
congenital adrenal hyperplasia
cushing syndrome
androgen secreting tumours
hyperprolactinaemia

16. HOW TO DIAGNOSE: PCOS
Rotterdam criteria for diagnosis
Two or more of the three following criteria:
• polycystic ovaries (either 12 or more peripheral follicles or
increased ovarian volume up to 10mm3)
1 • -via TVUS
• oligo- or anovulation (manifested as oligo- or amenorrhea)
2
• clinical and/or biochemical signs of hyperandrogenism.
3

17. CLINICAL AND/OR BIOCHEMICAL
SIGNS OF HYPERANDROGENISM
Clinical Biochemical
• Early sign-acne • Free serum
• Later develop testosterone
hirsuitism or level (not more
even male than 5nmol/L)
pattern alopecia

18. A raised luteinising hormone/follicle-
stimulating hormone ratio
(LH:FSH 2:1) is NO LONGER a
diagnostic criteria!!!!

19. SCENARIO
• Husband: Seminal fluid – severe
oligoasthenoteratoazoospermia
• Day 21 serum progesterone –
not ovulating
• Ovarian stimulating induction + IVF

20. PREPARATION: SEMEN SAMPLING
• Advice patient - abstinence from
sex and masturbation for 2 - 7
days prior
• collected in a private room near
the laboratory to limit the
exposure of the semen to
fluctuations in temperature and to
control the time between
collection and analysis
• semen sample needs to be
complete & should report any loss
of any fraction of the sample

21. COLLECTION: SEMEN SAMPLING
• obtained by masturbation and ejaculated
into a clean and wide mouthed container
• specimen container should be kept at
ambient temperature, between 20 C and
37 C
• placed on the bench or in an incubator (37
C) while the semen liquefies.

22. HOME: SEMEN COLLECTION
• Sample need to be completed. Report if
incomplete.
• Record the time of semen production
and sent to lab within 1H. Temperature
kept between 20 C and 37 C during
transport of sample
• Noted at report place of collection (home
/ outside the lab)

23. CONDOM: SEMEN COLLECTION
• Collected in a condom during sexual
intercourse
• Only special non-toxic condoms
designed used
• Information on how to use the
condom, close it, and send or
transport it to the laboratory.
• Record the time of semen production
and sent to lab within 1H. Temperature
kept between 20 C and 37 C during
transport of sample
• Noted at report place of collection
(home / outside the lab)

24. SEMEN ANALYSIS: WHO
Volume • > 1.5 mL
pH • ≥ 7.2
Total Sperm • 39 × 10^6 spermatozoa per
Number ejaculate
Sperm • 15 × 10^6 spermatozoa per ml
Concentration

25. SEMEN ANALYSIS: WHO 2010
• Sperm Motility :
– Progressive motility (PR): spermatozoa moving
actively, either linearly or in a large
circle, regardless of speed.
– Non-progressive motility (NP): all other patterns
of motility with an absence of progression, e.g.
swimming in small circles, the flagellar force
hardly displacing the head, or when only a
flagellar beat can be observed.
– Immotility (IM): no movement.
– Total motility (PR + NP) is 40%
– Progressive motility (PR) is 32%

26. SEMEN ANALYSIS: WHO 2010
• Sperm Vitality (membrane-intact
spermatozoa): 58% or more
• Sperm Normal Morphology (regular oval
head, with a connecting mid-piece and a long
straight tail): > 4%

27. NOMENCLATURE: WHO 2010
• Normozoospermia: total number of
spermatozoa, and % of progressively
motile (PR) and morphologically normal
spermatozoa ≥ lower reference limits
• Oligozoospermia: Total number of
spermatozoa <39 106 spermatozoa per
ejaculate or concentration of spermatozoa
<15 106 spermatozoa per ml
• Asthenozoospermia: Progressively motile
(PR) spermatozoa <32%

28. NOMENCLATURE: WHO 2010
• Teratozoospermia: < 4%
morphologically normal spermatozoa
• Azoospermia: No spermatozoa in the
ejaculate
• Aspermia: no semen (no or retrograde
ejaculation)

29. 3
WHAT DOES
MEAN?

30. OLIGOASTHENOTERATOZOOSPERMIA
• Total number/concentration of spermatozoa, and
percentages of both progressively motile (PR)
and morphologically normal spermatozoa, below
the lower reference limits

31. COMMENT ON THE
REASON OF USING
4 DAY 21
PROGESTERONE TEST

32. CRITERIA FOR TEST
1. Normal menstrual cycle
2. Length of menstrual cycle (28
days)
3. Not on hormonal therapy/OCP/
hormonal contraception 
interfere normal hormonal
changes
4. If on OCP, stop at least 1 month
before test

34. Ideal progesterone test done 21 days after
breeding
(Progesterone is high)

35. - Normal Day 21 progesterone level in
functioning corpus luteum > 30ng/ml
- ↓ Day 21 progesterone level 
Anovulatory cycles (no ovulation & no corpus luteum
formation to secrete the progesterone)
Abnormal menstrual cycle
Length of the menstrual cycle
On hormonal therapy/OCP/ hormonal contraception

36. WHAT ARE THE POSSIBLE
ASSOCIATED WITH
5

37. INDICATIONS OF IVF
• Tubal problems: blocked or damaged
Fallopian tubes
• Severe endometriosis
• Pelvic inflammatory disease with
severe adhesion
• Male factor
• Unexplained infertility

38. COMPLICATIONS OF IVF
• IVF is basically a safe procedure.
• As with any medical or surgical procedure, a
few patients undergoing IVF treatment will
experience side effects and complications.
• The most common complications associated
with IVF treatment are the:
Failure of treatment The possibility of ectopic
pregnancy.
Ovarian hyperstimulation
Bladder, bowel injury and other
Multiple pregnancy, risk related to egg retrieval

39. WHAT IS IVF?
The steps of IVF are as follows:
• Ovulation Induction
• Retrieval
• Insemination of eggs and embryos culture
• Transferring embryos to the uterus

40. OVULATION INDUCTION
• optional if women can ovulate normally
• the stimulatory phase of an IVF cycle must begin
on the third day of the menstrual cycle.
• patients receive daily injections of gonadotropins
– hormones, which stimulate your ovaries to
produce multiple eggs.
• The ultimate goal of IVF stimulation is to achieve
the maximum number of mature follicles- eggs-
without over stimulation.

41. OVARIAN HYPERSTIMULATION SYNDROME
(OHSS)
Mild to Moderate
majority of women have a mild or moderate form of the
syndrome and invariably resolve within a few days unless
pregnancy occurs, that may delay recovery.
complain of pain, a bloated feeling and mild abdominal
swelling.
In a small proportion of women, the degree of discomfort

42. OVARIAN HYPERSTIMULATION SYNDROME
(OHSS)
Severe
Very rarely is severe and the ovaries are very swollen.
The woman will feel ill, with nausea and vomiting, abdominal pain.
Fluid accumulates in the abdominal cavity and chest, causing abdominal
swelling and shortness of breath. Reduction in the amount of urine
produced.
These complications require urgent hospital admission to restore the fluid
and electrolyte balance, monitor progress, control pain and in some very
serious cases, termination of pregnancy.
Complications associated with severe OHHS include blood clotting
disorders, kidney damage and twisted ovary (ovarian torsion).

43. CAUSES OF OHSS
Women with polycystic ovaries.
Over response to fertility drugs.
Young thin women.
High estrogen hormone levels and a large number of
follicles or eggs.
Administration of GnRh agonist.
The use of hCG for luteal phase support.

44. RETRIEVAL
When the eggs are
“ready”, that is, the majority Mature eggs will be collected
that we ask the male partner
of eggs are ripe for by ultrasound guided needle
to produce a semen sample
harvesting but they are not aspiration.
yet truly mature.
Retrieval is done after at
least 3 mature follicles of 18 It is at this time, shortly
This technique is performed
mm or more to produce a rafter the conclusion of the
in the office with IV sedation.
mature egg, a final injection egg retrieval,
must be taken.
minor surgical-Follicles are
located by ultrasound and
then a needle is guided
This final shot is called HCG.
through the vaginal wall into
the ovary to aspirate the
eggs from the follicles.

46. INSEMINATION OF EGGS AND
EMBRYO CULTURE
ICSI IVF
intracytoplasmic sperm
injection In-Vitro Fertilisation
inject a single sperm into each egg. decision regarding the number of embryos to
transfer is not always easy
48 hours the fertilized eggs – now depends on such things as patient age, past IVF
called embryos – will be left alone in cycles and the quality of the embryos.
the incubator- for 3 to 5 days.
objective is to maximize the chance of pregnancy
the embryos will have been carefully while minimizing the chances of multiple
examined pregnancies.

47. TRANSFERRING EMBRYOS TO
UTERUS
the embryos will be transferred by placing very small
flexible catheter into your cervix and injecting the
embryos.
continue to take Progesterone (shots, pills or
pessaries)
A pregnancy test will be done 2 weeks after the
transfer
If the test is positive Progesterone shots are continued
as instructed (serum B-HCG).

50. 6TH WEEK AFTER IVF
• c/o lower abdominal pain associated with
per vaginal bleed for 2/7
• pain more marked on right side radiated
to the back
• vomited several times
• pain temporarily relieved by analgesia

51. ON EXAMINATION
• Blood pressure: 90/60 mmHg (↓)
• Pulse rate: 110 beats per minute (↑)
• Abdomen examination: tender on the
right iliac fossa (RIF) with no mass
palpable
• Vaginal examination: cervical os was
closed with some old blood seen on
posterior fornix
• Minimal cervical excitation and no
adnexal mass palpable

52. 6 LIST 4

53. Ectopic pregnancy
• Pregnancy occurring in sites other than endometrium of the
uterus.
Threatened miscarriage
• Vaginal bleeding (usually fresh bleed and painless) with a closed
cervix prior to 22 weeks of pregnancy
Molar pregnancy
• Pregnancy in which a hydatid mole develops from the
trophoblastic tissue of the early embryonic stage of development
Impending miscarriage (inevitable)
• Onset of miscarriage process and will end as either
complete, incomplete or septic miscarriage

54. 7
COMMENT THE
ULTRASOUND
FINDINGS?

55. a gestational sac extra uterine
Empty uterus, free fluid in pouch of
Douglas (POD)

57. RUPTURED
ECTOPIC
PREGNANCY

58. EVENTUALLY
• An emergency laparatomy was done and
found to have 2 litres of haemoperitonium
and ectopic pregnancy of right tube.
• Subsequently, right salphingectomy was
done and she was discharged after 3 days
from ward.

59. THANK
YOU