IVM is ready as a treatment for PCOS patients

Dr. Milton Leong MDCM DSc (McGill)

Director, IVF Center, HKSHAdjunct Professor, OBS-GYN, McGill University

1

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 2002 2004

PCOS

• Ovulation Induction:

• Low dose - reduced response• Higher dose - over-response• Leading to multiple pregnancies• Higher risk OHSS

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

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

PCOS, OHSS and IVF

• Risk up 5-30 fold (6-30%)

• Estradiol >3000pg/ml

• # Follicles >20

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

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. 1991 : 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).

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

IVM/IVF vs IVF for PCOS

Child TJ, et al,2002

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 0%

A. Fukuda et al, Fertility & Sterility 2008

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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)

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GnRHa v.s. HCG in IVF-IVF used in PCOS

300 ųg Buserelin vs 10000 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

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Pregnancy Outcome in IVM

• Malformation:– Cha, Fertil. Steril. 2005 5,3% major

malformation rate

• Later neuromotor development:– Soderstrom-Anttila, Hum. Reprod. 2006

))) Minor developmental delay at first year

))) No Difference in the second year

Known live deliveries from IVM/IVFKorea 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 8

Total 930

McGill IVM results by age group (own oocytes only – patients with PCO or PCOS)

Age

(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% 20.0% 20.0%

38-40 5.0% 20.0% 10.0%

Results of IVM from Shin Kong Wu Ho-SuMemorial Hospital, Taipei, Taiwan*

Cycles 68Age 31.3 ± 4.1No. of oocytes collected 1,528 (21.9 ± 9.4)% of oocyte maturation 72.5%% of fertilization 75.8%% of cleavage 89.4%Mean of embryos transferred 3.8 ± 0.9No. of clinical pregnancies (%) 23 (33.8)% of implantation 11.3%% of OHSS <1%

* Data from Dr. Lin & Dr. Hwang (2003)

IVM/IVF in PCOS

Conclusions:1. PCOS is associated with OHSS2. OHSS = 80% post EC hospital admissions3. IVM/IVF is an established clinical technique4. IVM/IVF can reduce incidence of OHSS5. IVM/IVF can now be the treatment of choice for PCOS

in IVF