Minimising IVF related mortality and morbidity. Scott Nelson Muirhead Professor in Obstetrics & Gynaecology

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1 Minimising IVF related mortality and morbidity Scott Nelson Muirhead Professor in Obstetrics & Gynaecology

2 We rarely say no - so what I will cover today VTE as an example of a modifiable IVF complication How we can predict IVF outcomes How we can reduce the risk of multiple pregnancy How we can personalise treatment and minimise risk for your patients

3 How we do IVF Van Voorhis et al N Engl J Med 2007

4 VTE as an example of an IVF modifiable complication

5 ART increases the risk of VTE Henriksson et al. BMJ 2013

6 ART increases the risk of pulmonary embolism Henriksson et al. BMJ 2013

7 VTE in ART is a first trimester phenomenon First Second Third Postnatal Trimester Rova et al Fertil Steril 2012

8 The VTE risk factors are potentially modifiable Fresh IVF No OHSS Fresh IVF + OHSS FET >40y BMI >30kg/m 2 Multiple pregnancy Rova et al Fertil Steril 2012

9 Reducing the risk of VTE obesity Aggressive stimulation hcg Fresh transfer of multiple embryos OHSS Older women We can change these

10 How we can predict IVF outcomes

11 We can predict live birth using IVFpredict.com 144,000 fresh IVF cycles Baseline characteristics Freely available Nelson and Lawlor PLOS Medicine 2011 IVFpredict.com

12 Live birth rate IVFpredict now externally validated on 130,960 cycles Observed Predicted Deciles of risk Te Velde et al Hum Reprod 2014 Smith et al submitted

13 The big challenge of assessing variability Sarah Oocyte number Melisa Age Wallace and Kelsey PLOS One 2010

14 AFC and AMH can help us predict ovarian reserve Iliodrimiti et al Hum Reprod Update 2014

15 AFC AMH Both indicate a woman s ovarian reserve at any age Age Age La Marca et al Fertil Steril 2011 Nelson et al Fertil Steril 2014

16 Both help us predict oocyte yield Chang et al Fertil Steril 1998 Nelson et al Hum Reprod 2007

17 Both help us predict extremes of ovarian response Poor Excessive Broer et al Fertil Steril 2008 Broer et al Hum Reprod Update 2011

18 We can modify ovarian response GnRH agonist approach Maximal follicular recruitment Side effects Robust Significant OHSS FSH Level Follicle size (mm) GnRH antagonist approach Reduced follicular recruitment Shorter Equivalent live births Fewer oocytes and embryos GnRH agonist trigger Reduced or no OHSS Macklon, et al. Endocrine Reviews Fauser, et al. Hum Reprod

19 We can stratify treatment and minimise risk Nelson et al Hum Repro 2009 Nelson et al. Fertil Steril 2013

20 We can use a GnRH agonist trigger to mature oocytes LH surge after GnRHa trigger Humaiden et al. Hum Repro Update 2011 Iliodromiti et al. Hum Reprod 2013

21 If we use a GnRHa trigger we will eliminate early OHSS Humaiden et al. Hum Repro Update 2011

22 Ovarian stimulation adversely affects endometrium Normal High progesterone Labarta, et al. Hum Repro 2011

23 We can segment cycle and improve perinatal outcomes Risk Ratio 95% CI Antepartum haemorrhage 0.67 (0.5, 0.81) Preterm labour 0.84 (0.48, 0.90) Small for gestational age 0.45 (0.30, 0.66) Low birth weight 0.69 (0.62, 0.76) Perinatal Mortality 0.68 (0.48, 0.96) Maheshwari et al. Fertil Steril 2013

24 How we can reduce the risk of multiple pregnancy

25 We can use extended culture to select embryo Day 1 Day 2 Day 3 Day 4 Day 5 Day 5 / 6 Pronuclear stage Blastocyst

26 Many blastocysts will still be chromosomally abnormal CGH results of 1218 cleavage-stage embryos embryos from 203 women Ata et al. RBMOnline 2012

27 We can use time lapse to select the correct blastocyst Embryoscope at Glasgow Royal Infirmary

28 We can limit the number of embryos we transfer Lawlor and Nelson Lancet 2012

29 We can limit the number of embryos we transfer Lawlor and Nelson Lancet 2012

30 But in the US more is still thought to be better Donor oocyte outcomes Year Year Kulkarni et al NEJM 2013 Kawwass et al JAMA 2013

31 How we can personalise treatment and minimise risk

32 Delivery rate at first cycle Cumulative delivery rate We need to be prepared to repeat IVF safely Maternal age Cycle number N=271,438 IVF cycles Smith et al submitted 2014

33 A safe approach to women with medical complications Use GnRH antagonist strategy GnRH agonist trigger Culture all embryos to blastocyst and freeze Replace single embryo in frozen cycle Completely removes OHSS and VTE risk Nelson et al Hum Reprod 2012

34 A safe approach to women with medical complications Use GnRH antagonist strategy GnRH agonist trigger Culture all embryos to blastocyst and freeze Replace single embryo in frozen cycle Completely removes OHSS and VTE risk Reduces multiple risk and adverse perinatal outcomes Nelson et al Hum Reprod 2012