Dr Guy GudexDirector

Repromed

15:00 - 15:15 Assisted Reproduction 2020

Assisted Reproduction 2020

Dr Guy Gudex

ART in NZ -2014 ACART Report

• 5,891 ART cycles

• Average age women 35.6y 22% aged 40 or more

• SET rate – 84% fresh ET (70% 2012) 97% thaw (91% 2012)

• Multiple pregnancy rate 3.4 % (5.1% 2012)

The OHSS free clinic

17%

23%

29%

0%

5%

10%

15%

20%

25%

30%

35%

2015 2016 2017

Pe

rce

nta

ge

Years

Repromed Percentage of Freeze Only Cycles per OPU

Reduction of OHSS risk prior to cycle commencement

• Higher dose of FSH used during ovarian stimulation is associated with increased risk of OHSS

• Use of GnRH antagonist rather than GnRH agonist during ovarian stimulation for ART reduces the incidence of OHSS

• Concomitant use of metformin in women with PCOS undertaking an IVF or ICSI cycle reduces the incidence of OHSS

D1 (Period)

D7 D13(TVOR)

D18(ET)

D29(bhCG test)

rFSH

antagonist

Duration: 4 weeks, 3 visits to clinic (D9 scan, TVOR, ET).

B/S

Antagonist cycle – the key to “patient friendly” IVF

Current Methods of Embryo Selection

Invasive

• Preimplantation Genetic Screening (Only method to screen for Aneuploidy)

Non-Invasive

• Embryo Morphology (primary / widely used)

• Time-Lapse kinetics• Metabolomics

Aneuploidy – Why bother?

Dramatic decline in IVF success rates with maternal age is mainly caused by embryonic aneuploidy(Hassold et al., 1996; Vialard et al., 2011)

EmbryoSelect @ Repromed

• Repromed now offers ‘EmbryoSelect’ which is Pre-implantation Genetic Screening (PGS) using Next Generation Sequencing (NGS)

• Identifies the most competent (euploid) embryos for transfer

• Indications for EmbryoSelect use in IVF include

✓ Advanced maternal age (>35y)

✓ Recurrent miscarriage

✓ Repeated implantation failure

Embryo Mosaicism

• Controversial topic

• May reflect inner cell mass and / or trophectoderm

• Several studies have shown normal babies born after detection of mosaicism up to 50%

Euploid Embryo – 46,XY

Aneuploid Embryo – 47, X0 (Trisomy 18 + one sex chromosome)

Trophectoderm Biopsy – with laser

Ovarian Reserve Testing AMH

• Single blood test done at any time in a menstrual cycle

• Patient should not be taking OC or depo provera

• Cost currently $90.00, result available within two weeks

• Repromed offering AMH testing to all patients including those presenting with RPL

>75% Percentile: Probable PCOS

25-75% Percentile: Normal Ovarian Reserve

<25% Percentile: Low Ovarian Reserve

AMH Profile

Anti Oxidants and Subfertility

Improving success rates in IVF Antioxidants

• Cochrane Review 2017 on oral antioxidants for female subfertility –increase in LBR compared to placebo

• Melatonin 3mg daily , COQ10 300mg daily, Green tea

• Anti oxidants mitigate mitochondrial DNA damage and

• Increase embryo quality

Improving Oocyte Quality

• Antioxidants

• Pre-treatment with testosterone – improves ovarian sensitivity to FSH

• Double trigger GnRH agonist and hCG

Fertility Preservation

• Significant progress in the development of egg freezing and thawing techniques with improved pregnancy rates - vitrification

• Random start IVF stimulation and dual stimulation protocols

• Restart FSH stimulation 5 days after OPU

Social Egg Freezing (SEF)

• Not an insurance policy against childnessness

• Average age in UK for SEF 38 years

• Alternative to sperm donation for single women

• Ideally done under the age of 35 years

Feb 2016

Case study

• Ms AB age 53

• Presented 2016 age 51 requesting donor egg IVF in USA

• History of LSCS 2007 age 44 – healthy baby girl

• Assessed by Obstetric Physician – advised to take low dose Aspirin, Calcium in early pregnancy to reduce pre eclampsia risk

• 24 yr old donor, SET – with 10 embryos cryopreserved

• Normal pregnancy and LSCS at term 2017 age 52

• Presents requesting assistance with FET in USA- has seen obstetric physician

Issues

• Maternal mortality – low but probably risk increased

• Maternal morbidity increased e.g. risk of hypertension 35% in women aged 50 yrs with egg donation pregnancy

• Still birth risk significantly increased in VAMA group

• Ethical concerns – patient right to choose treatment vs clinical right to refuse access

• Appropriate screening e.g. ECG, HbA1C, physician review, mammography

What should we be doing?

• Try and better adapt to the needs of working and/or future mothers.

• Creating better public awareness about age related reproductive decline and fertility preservation.

• Offer age specific information and counselling – women in their 20’s and 30’s should be counselled about the age related risk of infertility when they present for sexual health or contraception discussion.

• Offer predictive tests such as AMH or AFC.

• Try and convince those women who may benefit from SEF to present before the age of 35.

Endometrial receptivity

• New tests using microarray analysis of genes involved in

endometrial implantation

• Endometrial biopsy taken post ovulation

• Results expressed as pre-receptive, receptive or post-receptive

IVM at Fertility Specialists, Perth, Australia

• Current practice: Mainly PCO/S patients, 3x days FSH, no hCG, IVM in G2 medium + 10% serum, ICSI (or IVF), freeze all cycles, blastocyst SET.

• Retrospective analysis of IVM vs IVF (Walls M et al (2015) Hum, Reprod.)

0

1

2

3

4

5

IVM IVF

Me

an /

OP

U

Useable Blastocysts

0

10

20

30

40

IVM IVF

%

CPR (per FET)

0

10

20

30

40

IVM IVF

%

Live Birth Rate (per FET)

0

20

40

60

IVM IVF

%

Cumulative Live Birth Rate/OPU

Summary

• Improved embryo selection

• OHSS reduction

• Developments in understanding endometrial receptivity and implantation

• Social egg freezing increased demand

• Increased demand for ART in advanced maternal age group

• Access to public funded treatment reviewed as demand increases