1. IVM is ready as a treatment for PCOS patients
Dr. Milton Leong
MDCM DSc (McGill)
Director, IVF Center, HKSH
Adjunct Professor, OBS-GYN, McGill University

2. PCOS Commonest endocrine disorder in women
May be 80% anovulatory infertility?
Ovulation induction required
Most are clomiphene responsive
Cumulative pregnancy rates lower than non-PCOS patients
Balen

3. PCOS Ovulation Induction: Low dose - reduced response
Higher dose - over-response
Leading to multiple pregnancies
Higher risk OHSS

4. PCOS and IVF
IVF is an effective, may be preferred choice of therapy because of the problems associated with ovulation induction
Significantly more oocytes
Lower fertilization rate
Dor et al, Homburg et al Kodama et al

5. PCOS and IVF Pregnancies were comparable to non-PCOS patients
Increased miscarriage rate
FSH requirement leads to under or over response
Higher cancellation rate
Much higher chance of OHSS

6. PCOS, OHSS and IVF Risk up 5-30 fold (6-30%) Estradiol >3000pg/ml
# Follicles >20

7. OHSS in PCOS Undergoing IVF
Preventive Measures:
Pre-treat with laparoscopic drilling
Use GnRH-ant then GnRH-a to trigger
Metformin (as short as 28 days)
No Transfer, Cryopreservation
Early Aspiration of Follicles - 2 operations
Conversion to IVM
IVM with and/or without stimulation

8. Progress in IVM Edwards 1965 : 1st in vitro matured oocyte
Veeck 1983 : 1st IVM pregnancy from an ovum derived from a
stimulated cycle
Cha et al : the first pregnancy from in-vitro matured oocytes derived from a caesarean section donor
Trounson et al. 1994: IVM in women with PCOS
improvements in culture condition and transfer techniques have demonstrated that IVM is an effective treatment for women with PCO or PCOS.
In general, clinical pregnancy and implantation rates for infertile women with PCO or PCOS have reached approximately 30-35% and 10-15%, respectively, (Chian et al., 2004).
Since Cha et al. (1991) reported the first pregnancy from in-vitro matured oocytes derived from a caesarean section donor, fertilization, embryo development and pregnancy by immature human oocytes matured in-vitro have been successfully achieved in women with polycystic ovary syndrome (PCOS) (Trounson et al., 1994; Cha and Chian, 1998). Recent improvements in culture condition and transfer techniques have demonstrated that immature oocyte retrieval followed by IVM is an effective treatment for women with polycystic ovaries (PCO) or polycystic ovarian syndrome (PCOS)-related infertility because there are numerous antral follicles within the ovaries in this group of patients. In general, clinical pregnancy and implantation rates for infertile women with PCO or PCOS have reached approximately 30-35% and 10-15%, respectively, (Chian et al., 2004a, b).

9. Advantages of IVM No/minimal stimulation: less OHSS
less long term effect
safety factor – cancer patients
Flexible start time, no preparation
Cancer patients
no theoretical and actual risk (esp br ca)
can treat anytime

10. IVM is a useful treatment ,particularly for women with pcos
The majority of other groups have also reported low rates of success when performing ivm for women with normal ovaries.

11. IVM/IVF vs IVF for PCOS Child TJ, et al,2002
For women with pcos who required assisted conception, IVM is a promising alternative to conventional IVF treatment.
Child TJ, et al,2002

12. IVM-IVF in POS 210 cycles 1883 oocytes 56% maturation
83% fertilization
Pregnancy rate 31% fresh
32% frozen-thawed
50/56 pregnancies delivered
Miscarriage 11%
OHSS %
A. Fukuda et al, Fertility & Sterility 2008

13. Ovulation trigger
LH surge induced by GnRH agonist achieves identical clinical outcome as HCG in in vitro maturation, in vitro fertilization and embryo transfer (IVM-IVF)

14. GnRHa v.s. HCG in IVF-IVF used in PCOS
300 ųg Buserelin vs unit HCG
Maturation rate same (±50%)
Fertilization rate same 85%
Pregnancy rate same 41%
OHSS rate < 1%
A. Fukuda et al, Fertility and Sterility 2008

15. Pregnancy Outcome in IVM
Malformation:
Cha, Fertil. Steril ,3% major malformation rate
Later neuromotor development:
Soderstrom-Anttila, Hum. Reprod. 2006
))) Minor developmental delay at first year
))) No Difference in the second year

16. Known live deliveries from IVM/IVF
Korea
455
Taiwan 20
Colombia 7
Canada
131
Finland 52
Turkey 8
China 58
Japan 51
Vietnam 42
Hong Kong 18
Denmark 34
Italy 56 UK
Total
930

17. McGill IVM results by age group (own oocytes only – patients with PCO or PCOS)
(years)
Implantation rate per embryo
Clinical pregnancy rate per cycle started
Live birth rate per cycle started
<35
14.4%
34.8%
20.0%
35-37
5.4%
38-40
5.0%
10.0%

18. Results of IVM from Shin Kong Wu Ho-Su
Memorial Hospital, Taipei, Taiwan*
Cycles
Age ± 4.1
No. of oocytes collected ,528 (21.9 ± 9.4)
% of oocyte maturation %
% of fertilization %
% of cleavage %
Mean of embryos transferred ± 0.9
No. of clinical pregnancies (%) (33.8)
% of implantation %
% of OHSS <1%
* Data from Dr. Lin & Dr. Hwang (2003)

19. IVM/IVF in PCOS Conclusions: PCOS is associated with OHSS
OHSS = 80% post EC hospital admissions
IVM/IVF is an established clinical technique
IVM/IVF can reduce incidence of OHSS
IVM/IVF can now be the treatment of choice for PCOS in IVF