Antagonist ……..is the answer

Dr Santosh Gupta MS,FRM

Consultant Reproductive Medicine Manipal Ankur Reproductive Services

Evolving human wisdom

Use of antagonist is also evolving in the hands of doctors worldwide

IVF : Miracle of millennium

From 1978 till today…………….

• Natural cycle IVF

• 1980s learned the ART of LH surge control by GnRH agonist

• IVF became a global phenomenon “ BUT” a chapter of IVF related complications opened

Emergence of new Super HERO “ ANTAGONIST”

Mechanism of action

Commercially available

• Cetrorelix

• ganirelix

Advantages of GnRH antagonist

• Shorter duration of treatment

• Less injections

• Less consumption of Gonadotropins

• No flare up /no cyst formation

• No pituatory desensitization “more physiological”

• Lesser incidence of OHSS

Brussels Consensus 2006

Pyramid of evidence

Efficacy………

1a

Endometrial receptivity

Prapas et al 2009,rep biomed; prospective RCT

Oocyte from each donor shared between 2 different recipients

Recipients were randomly allocated to either receive antagonist concomitant to donor during endometrial priming (gp1) or solely continuing endometrial preparation (gp2)

GnRH antagonist administration during the proliferative phase at a dose of 0.25mg does not appear to adversely effect endometrial receptivity

GP1 GP2

Endometrium similar similar

Implantation rate 26.1% 24.4%

Clinical pregnancy rate 55.1% 59.1%

1b

Cochrane review 2002 Al Inany et al

Antagonist versus agonist

Inexperience of the centre

Use of antagonist in higher age group

Use of antagonist in “unfavourable prognosis a priori”

Cochrane 2006

Cochrane review and meta-analysis 2011

45 RCTs

7511 randomized women

Conclusion

The GnRH antagonist protocol is short and simple protocol

with a comparable live birth rate to long agonist protocol.It

is associated with a highly significant reduction in the

incidence of OHSS compared to the agonist protocol

therefore justifies a move away from the standard GnRH

agonist long protocol to a GnRH antagonist protocol

1A

Burden of treatment……OHSS

3 OHSS related death in 100000 ART cycles

“In 2003-2005, 4 deaths (of the 12) were due to OHSS”.

3 levels of safety

• Less incidence of OHSS(1a)

• Gives freedom to use GnRH agonist as a

trigger to replace hCG

• Use of antagonist in luteal phase

Preferred protocol in PCOS……….

Cochrane review2011

8 Trials with 783 PCOS women OHSS rate 10% lower in Antagonist group

1A

11

Poor Response…….

Friendly IVF

Human reproduction 2009

Reducing treatment stress

De Clark et al 2006 ,human reproduction

In a study involving 391 women who were undergoing IVF with the conventional long agonist protocol reported statiscally significantly more symptoms of depression during the week before stimulation than control patients who did not experience downregulation.

Newer challenges…mild IVF

Fertility preservation in cancer patients

Immediate treatment

Allows shortest deferral of radio/chemotherapy

Agonist protocol requires extra 2to 3 weeks

Lower estradiol level, best for hormone responsive cancer

Random start/luteul phase start stimulation

Soft/mild ivf

Crystal ball where we are heading ……….????

IN

Antagonist protocol

OHSS free clinic

OUT

Long agonist protocol

Severe OHSS

OHSS related death

Its antagonist only………..