shandong university shandong provincial hospital zi-jiang chen m.d., ph.d. center for reproductive...
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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
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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
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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
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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
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Safety issues in ovulation induction
ovarian hyperstimulation syndrome
multiple pregnancy
ovulation induction and tumor
ovulation induction and ovarian functional
lesion
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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.
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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