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Shandong University Shandong Provincial Hospital Zi-Jiang Chen M.D., Ph.D. Center for Reproductive Medicine Shandong China Jinan, China The Effect of PCOS Treatment on Ovarian Function

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Shandong UniversityShandong Provincial Hospital

Zi-Jiang Chen M.D., Ph.D.

Center for Reproductive Medicine

Shandong , China

Jinan, China

The Effect of PCOS Treatment on

Ovarian Function

Shandong UniversityShandong Provincial Hospital

Ovarian Functions and Influence Factors 1

2

PCOS treatment on the ovarian function3

PCOS infertility treatment

Shandong UniversityShandong Provincial Hospital

Ovarian Functions

Two main

functions

Produce oocytesovulation

Follicle : basic functional unit. Once recruitment –

one follicle maturation more atresia

Synthesize and secrete steroids

E2 P T

Shandong UniversityShandong Provincial Hospital

Ovary age

Age No. of oocytes Significance

At birth (1 ~ 2)×106 Determination of follicular pool

Reproductive time 5×105

Later in the 30s 2.5×104 Rapid decrease phase( Deterioration phase)

Up to 51 1000 Menopause

>51 Exhaustion of follicles End of female reproductive life

Shandong UniversityShandong Provincial Hospital

Influence Factors on Follicular Pool

Radio-therapy

Inflammation

Endometriosis Passive smoking

Smoking

Immune factors

Chemo-therapy

operation

Acquired factors

1 、 Genetic factors:

The size of follicular pool is

determined at birth, and

different among individuals

2 、 Acquired factors:

Damage or disease decreases

the follicular pool, as it may

decrease the ovarian cortex

or blood supply

Shandong UniversityShandong Provincial Hospital

Ovarian Functions and Influence Factors 1

2

PCOS treatment on the ovarian function3

PCOS infertility treatment

Shandong UniversityShandong Provincial Hospital

Evaluation of pre-treatment

Comprehensive Evaluation:

Treatment history

of infertility

Ovarian function

Female age

family history

Infertility cause

and duration

Shandong UniversityShandong Provincial Hospital

PCOS infertility treatment

Life style modification

Drug

Surgery

ARTOvarian function?

Shandong UniversityShandong Provincial Hospital

First line treatment

Life style:

Exercise, smoke and diet

Medicine: CC, Letrozole, Gn…

new technology: laparoscope, IVF , IVM …

Treatment Strategy For PCOS-----2

Treatment Strategy For PCOS

Second line treatment

Third line treatment

Shandong UniversityShandong Provincial Hospital

Ideal COH protocol

Idealized COH protocols:

• Simple, convenient, economic ;• High quality oocytes ;• Better acceptability of the endometrium ;• Higher implantation rate of single embryo ;• Avoid or reduce complication.

Shandong UniversityShandong Provincial Hospital

COH with mild stimulation

Low dosage Gn /HCG

LE/Gn/HCG

LE/HCGImproved

natural cycles

CC/Gn

/HCG

CC/HCG

Natural cycles

COH protocols

Limitation :more canceled cycles

Lower pregnancy rate

Simple, low cost

Mainly used for poor-responder ,

low-income patients

Shandong UniversityShandong Provincial Hospital

PCOS ovulation induction

anovulatary PCOS patient

Life style modification, body weight, smoking, etc.

Clomiphene ovulation stimulation

euglycemic agent

gonadotropin LOP or …

IVF

Shandong UniversityShandong Provincial Hospital

Outcome of CC/LE for PCOS patients in our center

Group Age Duration BMI FSH(IU/L) MC3d

LE/HCG 28.07±3.52 3.14±2.42 23.67±3.04 6.33±1.09

CC/HCG 28.73±2.96 3.47±2.75 24.81±3.02 6.96±1.45

 cycles Ovulation rate (%)

pregnancy Rate per cycle (%)

No. of mature follicles

Em Thickness on HCG day (cm)

E2 on HCG day (pg/ml)

 58  65.5*  13.8 1.077±0.28* 0.89±0.13* 267.88±37.64* 45  46.7  13.3  1.733±0.59  0.78±0.08 456.67±101.45

Shandong UniversityShandong Provincial Hospital

PCOS Surgical Treatment

Microinvasive

surgery

Laparoscopic

Wedge resection

ultrasound-guided immature follicle

aspiration

Ovary function Evaluation

Pros and cons of variety Surgical skills are critical

Laparoscopic

Ovarian drilling

Shandong UniversityShandong Provincial Hospital

Traditional Wedge resection

Flaws :•POF rate 20-80 %•Pelvic adhesion rate 40-75 %•Lead to irreversible infertility

Laparoscopic ovarian drillingFlaws :

Pelvic adhesion rate : 19%–82%

Ovulation dysfunction due to cicatricle

on the surface of ovary

Difficulty in control quality and depth

of drilling

Shandong UniversityShandong Provincial Hospital

a Ovary before puncture

b Reinspection two weeks after puncture

Schematic diagram for ultrasound mini invasive surgery

Ultrasound-guided immature follicle aspiration

( IMFA) to treat severe PCOS

Shandong UniversityShandong Provincial Hospital

Methods

PCOS ( 108 cases )

Preoperative use hMG ( 37 cases )

No use hMG( 71 cases )

IMFA2-3 cycles

No. of antrum follicles<10/ovary

hMG ovulation treatment

Shandong UniversityShandong Provincial Hospital

I group II groupage 27.9±3.6 28.9±2.4Infertile years 3.1±1.5 2.9±1.7Before

treatment

LH/FSH 2.5±0.2 2.1±0.6

T076.3±12.5 67.8±25.7

No. of antrum follicles 24.5±13.1 27.3±11.8After

treatment

LH/FSH 0.8±0.2* 1.2±0.6*

T036.8±16.5* 41.4±12.5*

Mean No. of antrum follicles

9.2±3.4* 8.9±2.7*

Mean Puncture times 2.38 2.56

Mean hMG doses (ampoule) Per cycle

20.8±6.3 22.6±10.5

With OHSS cases 0 2

pregnancy rate ( cases (%) ) 20 ( 54.1% ) 16 ( 47.1% )

Ultrasound-guided immature follicle aspiration

( IMFA) to treat severe PCOS

Shandong UniversityShandong Provincial Hospital

Advantages of ultrasound-guided immature follicle

aspiration for PCOS infertility treatment :

• Smaller lesion , safe , less pelvic adhesion• reduce OHSS risk by decreasing number of antral

follicles directly, • No risk of POF• Improve metabolic and endocrine status of PCOS patients

Shortage: temporarily, invasively

Shandong UniversityShandong Provincial Hospital

Ovarian Functions and Influence Factors 1

2

PCOS treatment on the ovarian function3

PCOS infertility treatment

Shandong UniversityShandong Provincial Hospital

The safety issue of

Clinical treatment for PCOS

PCOS patients

The safety during ovulation inductionThe safety during ovulation induction

The safety of minimally invasive surgery

(LOD, Transvaginal Ultrasound puncturation)

The safety in ART

Shandong UniversityShandong Provincial Hospital

Safety issues in ovulation induction

ovarian hyperstimulation syndrome

multiple pregnancy

ovulation induction and tumor

ovulation induction and ovarian functional

lesion

Shandong UniversityShandong Provincial Hospital

Ovulation induction and ovarian cancer

Rossing MA et al N Engl J Med. 1994 Sep 22;331(12):771-6

Whittemore AS et al Am J Epidemiol. 1992 Nov 15;136(10 .

3837 cases infertility patients for 7-18 years, shows that using

CC for over 12 months, the onset risk of ovarian cancer and

ovarian borderline tumor increased.

In patients with ovulation induction:

ovarian cancer elevated 2.8 folds, ovarian borderline tumor

increased 4 folds

Shandong UniversityShandong Provincial Hospital

33 cases with epithelial cancer

16 cases with borderline tumour

15 cases with granular cell tumor

1 case with malignant teratoma

Reports on ovarian tumor after ovulation induction

Average onset age is 30.3-year-old,which is 20 years earlier than normal onset age

Ali Mahdavi, et al. Farr Nezhat. 2006,85(4):819-826

Franco C,et al. 2000 Apr;52(4):103-9.

Shandong UniversityShandong Provincial Hospital

Can repeated stimulated ovulation influence ovarian reserve by excessive consumption of follicles?

Can it influence normal menstrual cycle and even if cause premature menopause?

For PCOS patients , superovulation can only decrease Antral Follicle Numbers and ameliorate menstrual cycle for a short time, no influence on ovarian reserve function

Nikolaou D et al. Hum Reprod. 2002 Apr;17(4):1106-11. de Boer EJ et al. Fertil Steril. 2002 May;77(5):978-85

Ovulation stimulation and ovarian reserve

Shandong UniversityShandong Provincial Hospital

• Repeated superovulation is non-physiological stimuli, over

consumption of follicle may exceed physiological limit

• So far, no strong evidence show a adverse influence on ovarian

reserve

• Mild stimulation schemes has been advocated

• large sample studies are needed in the future

Ovulation stimulation and ovarian reserve

Shandong UniversityShandong Provincial Hospital

Take home messages

Treat PCOS patients with

Minimum cost

Maximum efficiency

Never forget to treasure ovaries!

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