pcos and infertility

PATHOLOGICALCLINICO-

CORRELATION

SUPERVISOR:DR. TAN NUGROHOCIPTO RIYANTO

MOHD

HANAFISURYA

RAJMICHAEL

WONGANGEL

KWANNUR

AINURAFATIN

AKMALCPC

Infertility is defined as failure to conceive after one year of unprotected coitus at frequent intervals.

Primary Infertility

happened in woman who has never conceived

Secondary Infertility

happened in a woman who has conceived before

DEFINITION: INFERTILITY

AETIOLOGY: INFERTILITY

Unexplained infertility; 28

Male factor; 21Ovulatory disorder; 18

Tubal diseases; 14

Endometriosis, Fibroid; 9

Coital problems; 5

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)

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)

COMMENT THE

FINDINGS?ULTRASOUND

1

WHAT IS THE SUGGESTIVE

AND HOW TO DIAGNOSE

THAT DISEASE?

2

DIAGNOSIS?

POLYCYSTICOVARIAN SYNDROME

• 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

WHAT IS 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

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.

PATHOPHYSIOLOGY: PCOS

• Rotterdam criteria for diagnosis• The diagnosis of PCOS requires the

exclusion of all other disorders that can result in menstrual irregularity and hyperandrogenism:

HOW TO DIAGNOSE: PCOS

congenital adrenal hyperplasia

cushing syndrome

androgen secreting tumours

hyperprolactinaemia

1

• polycystic ovaries (either 12 or more peripheral follicles or increased ovarian volume up to 10mm3)

• -via TVUS

2• oligo- or anovulation (manifested as oligo- or amenorrhea)

3• clinical and/or biochemical signs of hyperandrogenism.

Rotterdam criteria for diagnosisTwo or more of the three following criteria:

HOW TO DIAGNOSE: PCOS

Clinical

• Early sign-acne• Later develop

hirsuitism or even male pattern alopecia

Biochemical

• Free serum testosterone level (not more than 5nmol/L)

CLINICAL AND/OR BIOCHEMICAL

SIGNS OF HYPERANDROGENISM

A raised luteinising hormone/follicle-stimulating hormone ratio (LH:FSH 2:1) is NO LONGER

a diagnostic criteria!!!!

SCENARIO

• Husband: Seminal fluid – severe oligoasthenoteratoazoospermia

• Day 21 serum progesterone – not ovulating

• Ovarian stimulating induction + IVF

• 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

PREPARATION: 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.

COLLECTION: SEMEN SAMPLING

• 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)

HOME: 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)

CONDOM: SEMEN COLLECTION

SEMEN ANALYSIS: WHO

• > 1.5 mLVolume

• ≥ 7.2pH

• 39 × 10^6 spermatozoa per ejaculate

Total Sperm Number

• 15 × 10^6 spermatozoa per mlSperm Concentration

• 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%

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%

SEMEN ANALYSIS: 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%

NOMENCLATURE: WHO 2010

• Teratozoospermia: < 4% morphologically normal spermatozoa

• Azoospermia: No spermatozoa in the ejaculate

• Aspermia: no semen (no or retrograde ejaculation)

NOMENCLATURE: WHO 2010

WHAT DOESOLIGOASTHENOTHERATOZOOSPERMIAMEAN?

3

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

OLIGOASTHENOTERATOZOOSPERMIA

COMMENT ON THEREASON OF USING

DAY 21PROGESTERONE TESTTO CHECK OVULATION?

4

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

CRITERIA FOR TEST

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

- 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

5

WHAT ARE THE POSSIBLE

COMPLICATIONSASSOCIATEDWITH

IVF?

• Tubal problems: blocked or damaged Fallopian tubes

• Severe endometriosis• Pelvic inflammatory disease with

severe adhesion• Male factor• Unexplained infertility

INDICATIONS 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:

COMPLICATIONS OF IVF

Failure of treatment

Ovarian hyperstimulation

Multiple pregnancy,

The possibility of ectopic pregnancy.

Bladder, bowel injury and other risk related to egg retrieval

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

WHAT IS IVF?

• 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.

OVULATION INDUCTION

OVARIAN HYPERSTIMULATION SYNDROME (OHSS)

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

Mild to Moderate

OVARIAN HYPERSTIMULATION SYNDROME (OHSS)

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).

Severe

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.

CAUSES OF OHSS

When the eggs are “ready”, that is, the majority of eggs are ripe for harvesting but

they are not yet truly mature.

Retrieval is done after at least 3 mature follicles of 18

mm or more to produce a mature egg, a final injection

must be taken.

This final shot is called HCG.

minor surgical-Follicles are located by ultrasound and

then a needle is guided through the vaginal wall into the ovary to aspirate the eggs

from the follicles.

It is at this time, shortly rafter the conclusion of the egg

retrieval,

that we ask the male partner to produce a semen sample

Mature eggs will be collected by ultrasound guided needle

aspiration.

This technique is performed in the office with IV sedation.

RETRIEVAL

ICSI

intracytoplasmic sperm injection

inject a single sperm into each egg.

48 hours the fertilized eggs – now called embryos – will be left alone in

the incubator- for 3 to 5 days.

the embryos will have been carefully examined

INSEMINATION OF EGGS AND EMBRYO CULTURE

IVF

In-Vitro Fertilisation

decision regarding the number of embryos to transfer is not always easy

depends on such things as patient age, past IVF cycles and the quality of the embryos.

objective is to maximize the chance of pregnancy while minimizing the chances of multiple

pregnancies.

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).

TRANSFERRING EMBRYOS TO UTERUS

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

• 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

ON EXAMINATION

DIAGNOSIS

POSSIBLE

-RELATED

PREGNANCY

LIST 46

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

7COMMENT THE

FINDINGS?ULTRASOUND

Empty uterus, free fluid in pouch of Douglas (POD)

a gestational sac extra uterine

ECTOPICDX

PREGNANCY

RUPTURED

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.

THANKYOU