Management of Women with - PowerPoint Presentation

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Management of Women with

Clomiphene

CitrateResistant Polycystic Ovary Syndrome

DR

Seyed

Mehdi Ahmadi

OB & Gynecologist

Isfahan Fertility & Infertility CenterSlide3

Indications

I. Ovulation induction: in the following cases:

a) C.C resistant PCO: Defined as failure to ovulate on a dose of 100 mg, for 5 days (recently in 3 cycles, in contrast to 6 cycles in the past ) orfailure to ovulate on incremental doses of CC(50-150mg).

b)

C.C failure PCO

:

Defined when pregnancy does not occur despite of regular ovulation on C.C for 6-9 cycles.

c)

C.C pregnancy failure:

Defined as failure to maintain pregnancy conceived with C.C.Slide4
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Various treatment modalities

Tre PharmacologicalCC

Gonadotropin

Hyperinsulinemia

? hMG Insulin sensitizer uFSH GnRH-analogs HP-FSH rec-FSHSlide7

A. Medical Treatment

Infertility is treated by increasing the rate of ovulation, in part by reducing insulin drive through exercise and weight loss .

Ovarian stimulation is used for those patients who do not ovulate, despite loosing weight by different drugs and different protocols.Slide8

Medical Treatment (cont.)

Treat

Hyperprolactinaemia with Bromocriptine.Glucocorticoids for adrenal hyperplasia . ( 0.25mg Dexamethasone at night )

COC pills or POP for dysfunctional uterine bleeding and to reduce the risk of endometrial

carcinoma

. Slide9

B. Surgical treatment modalities

Surgical Treatment

Cauterization Wedge resection ( laser, electric ) Slide10

Methods of Ovarian Surgery For Ovulation Induction In PCOS

Laparoscopic Techniques of Ovarian Surgery (LOS)

Laparoscopic Ovarian Drilling (LOD) : Diathermy / LASER. Transvaginal Techniques of Ovarian Surgery (TVOS)

1)

Transvaginal

mini-laparoscopy (Fertiloscopy)

2)

Transvaginal

ultrasound (TVS)-guided ovarian drilling. Slide11

LASER versus

electrocautery

for LOS:Electrocautery IS superior why?

1) Less coast &easy application.

2) Achieve higher ovulation and pregnancy rate.

3) Less surface injury than CO2 LASER → Surface adhesion.

4) Effect of diathermy may last longer than the effect of LASER . Slide12

1)

lifestyle modifications :Weight lossC

affeine intake

A

lcohol consumption

Smoking

D

ietary modification

ExercisePsychosocial stressorsSlide13

Role of weight loss in PCOS treatment:

R

educe insulin resistance by about 50%

R

estore ovulation

R

egulate menstrual cycles

R

educe pregnancy complications

I

mprove fertility

I

mprove health during pregnancy

I

mprove the health of a child during pregnancy

I

mprove emotional health (self-esteem, anxiety, depression)

R

educe risk factors for diabetes and heart diseaseSlide14

PROTOCOLS OF MANAGEMENT IN ADOLESCENTS

Counselling

for weight reduction and life style modification.Carbohydrate and fat restricted diet.Diet restriction and exercise is the sheet anchor of treatment for overweight.Low glycemic index diet upto 85% will improve menstrual cycle regularity and ovulation in about six monthsSlide15

Even 7% weight reduction may lead to spontaneous resumption of menses

.

Moderate physical activity, 30-60 minutes per day should be goal of all patient with adolescent PCOS.M.O.A:-lowers circulating free androgen and insulin levels.Increases SHBG, thereby decreases level of free testosterone.Slide16

FSH Ovulation Induction Protocol

Increase dose slowly - can be very sensitive

25-50iu/day

Increase dose

by 50%

Increase dose

by 50%

Starting

dose

Scan

d14

Scan

d7

Scan

d21

hCG 5000u

Follicle

=16mmSlide17
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2) Gonadotrophins :

Ovulation

induction with gonadotrophins has been used as a second line treatment for CC-resistant PCOS women.Disadvantage : expensive/ requires extensive monitoring /risk for OHSS & multiple pregnancy .The high sensitivity of the

PCOS to

gonadotrophic stimulation

is: they

contain twice

the number

of

FSH -sensitive antral follicles than the normal ovary.A lowdose,step-up gonadotrophin therapy should be preferred.Slide19

R

ecommended

approach is : begin with a low dose of gonadotrophin, (typically 37.5– 75 IU/day) increasing after 7 days or more if no follicle >10 mm has yet emerged, in small increments, at intervals, until evidence of progressive follicular development is observed.The maximum required daily dose of FSH/hMG seldom exceeds 225

IU/day.

There is

no evidence of a difference between recombinant FSH (

rFSH

) and

uFSH

for ovulation induction in CC- resistant PCOS women.Slide20

3)

Laparoscopic

Ovarian Drilling WHO BENEFITS FROMMechanism LEOS • ?Removalresistant, CC androgen-producing tissueProblems Slim, Anovulatory ,

•

Hazards of laparoscopic surgery & GA (although rare) raised S.LH

•

TemporaryEfficacy

•

<50% clomiphene-resistant women conceive (ovulation rate 80%+) • Hormone profile returns to normal • ?Fewer miscarriages compared to gonadotrophin injection treatmentSlide21

3)

Laparoscopic Ovarian

Drilling (LOD):

Being

as effective as

gonadotrophin treatment

and is not associated with an increased risk of multiple pregnancy or

OHSS.

When applied properly

, does not seem to compromise the ovarian reserve in PCOS women.n economic evaluation has shown that the cost of a live birth after LOD is approximately one-third lower than the equivalent cost of gonadotrophin treatment.Four punctures per ovary using a power setting of 30 W applied for 5s per puncture.Slide22

Unilateral LOD

being equally efficacious as bilateral drilling in inducing ovulation and

achieving pregnancy in CC resistant PCOS patients and may be regarded as a suitable option with the potential advantage of decreasing the chances of adhesion formation.Mechanism :LOD drains the ovarian follicles containing a high concentration of androgens and inhibin reduction of blood androgens and blood inhibin resulting in an increase of FSH and recovery of the ovulation

function .Slide23

poor responders to

LOD :

Women with marked obesity (BMI >35 kg/m2)Marked hyperandrogenism (serum testosterone concentration >4.5 nmol/lfree androgen index (FAI) >15long duration of infertility (>3 years

)

Predictor of higher probability

of

pregnancy :

LH levels >10 IU/l in LOD respondersSlide24

Technique of Laparoscopic Ovarian DrillingSlide25

4)

Insulin-sensitizing

drugs :Slide26

IMPROVEMENT OF HYPERINSULINEMIA BY INSULIN SENSITIZERS

Directly

sensitizing insulin receptors.Preventing neoglucogenesis.Reducing absorption of glucose from intestine.Increasing hepatic synthesis of SHBG level thereby reducing the level of bioactive free testosteroneSlide27
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Metformin

Decreases

basal hepatic glucose output in patients and lowers fasting plasma glucose concentration.It increases the uptake and oxidation of glucose by adipose tissue as well as lipogenesis.S/E- diarrhoea, nausea, vomiting ,specially initially. To avoid them metformin should be taken with meals and the dose increased gradually. Or SR release formulations are used once a day 1000 mg SR or 500mg SR twice a daySlide29
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OTHER DRUGS WHICH CAN BE USED

•

Rosiglitazone ,• Pioglitazone,• D chiro inositol,• Myoinositol• N acetyl cysteine.

•

Micronutrients Slide31

OTHER DRUGS WHICH CAN BE USED IN ADDITION TO O.C.P

In

cases of failure or where there is clinical or biochemical evidence of gross hyperandrogenicity or hyperinsulinemia, addition of metformin is recommended.Spironolactone- it has antiandrogenic effects in doses 100-200 mg daily.Finasteride - a competitive inhibitor of Type-2 5a reductase to treat hirsutism. Dose 1-5 mg/day. Slide32
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5)

Third-generation aromatase

inhibitors :Anastrozole, L

etrozole

,

E

xemestaneSlide38
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DURING PREGNANCY

RECURRENT

MISCARRIAGES 50%GESTATIONAL DIABETESPREGNANCY INDUCED HYPERTENSIONINTRAUTERINE GROWTH RETARDATIONSlide40

6)

Oral

contraceptives : Oral contraceptive administration

reduce serum LH, estradiol and androgen

levels

improving the

ovarian microenvironment

Inhance

ovarian response to CCSlide41

7) N-acetyl-cysteine :

N

-acetyl cysteine (NAC) is the acetylated variant of the amino acid L-cysteine.It is an excellent source of sulfhydryl groups and is converted in vivo into metabolites that stimulate glutathione production, promote detoxification, and act directly as free-radical scavengers.combination of CC and NAC increases ovulation and pregnancy rates in CC-resistant PCOS patients who also suffer from infertility.NAC has antiapoptotic

effects on the ovary and apoptosis is definitely responsible for the process of follicular atresia.Slide42

Biological activities of N-acetyl cysteine Slide43

8)

Dexamethasone

therapy : Dexamethasone (after 2 weeks of treatment )

Reduced DHEAS

R

educed

Testostrone

R

educed LH levels and the LH/FSH ratioInhance ovarian invironmentSlide44

9) Bromocriptine :

Bromocriptine administration provided

no benefit in CC-resistant PCOS patients with normal prolactin levels.Bromocriptine administration improve ovarian response in hyperprolactinemic patients.

Dopaminergic components have control

of LH release in PCOS patients

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10) IVF/ET or IVM :

If all else fails for the infertile PCOS patient then in-vitro fertilization is a last resort providing excellent results.Slide46

33-50% OF PATIENTS REFERRED FOR IVF HAVE PCOSSlide47
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MANAGEMENT

life

style and exercisesdietinsulin sensitisersocp’sprogesterone for bleedstatins/diabetes /antihypertensives if neededomega 3 and micronutrients(inositol or

myoinositol

or n-

actyl

cysteine or alternative medicines Slide49

Algorithm for ovulation induction treatment in

anovulatory

infertile women with CC-resistant PCOS Slide50
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