Dr Guy GudexDirector

Repromed

17:00 - 17:30 Recent Advances in Fertility Management

Recent Advances in Fertility Management

Practice Nurses Programme NZMA GP CME

June 2018

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

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

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%

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.

Genetic Carrier Screening

• The primary goal of carrier screening is to facilitate informed reproductive decision making by identifying those couples at risk of having an affected child with an (autosomal or X-linked) recessive disorder.

• Expanded carrier screening offers carrier screening for multiple recessive disorders, facilitated by new genetic testing technologies that enable the expansion of screening without significantly higher costs. An increasing number of commercial laboratories already offer expanded carrier screening.

• Current VCGS test offers screening for CF, Fragile X, SMA

Oral Ovulation Induction Agents

Metformin

• Taken orally 2-3 x daily (500mg tds or 850mg bd)

• Increase menstrual cyclicity and restore spontaneous ovulation

• Associated with modest weight losses, may help acne/hirsuitism

• GI side effects limit use

• Cheaper and more convenient as cycle monitoring is unnecessary

• No increase in multiple pregnancy rates

Clomiphene/LetrozoleClomiphene

• Used for OI for >50 years

• Taken daily (50-150mg) for 5 days during follicular phase

• Side effects hot flushes, nausea, breast tenderness, mood swings, (headaches/blurred vision rarely)

• Risks twins 7-9%, triplets 0.3%, OHSS <1%

• 15-20% of patients “CC-resistant”

Letrozole

• Aromatase inhibitor, used “off license” for ovulation induction

• Taken daily (2.5-7.5mg) for 5 days during follicular phase

• More favourable effects on endometrium

• Side effects fatigue and dizziness (but less than with CC)

• Risks twins <5%, 1 case sextuplets

Intrauterine Insemination

• Procedure in which washed and concentrated motile sperm is placed directly into the uterine cavity, just prior to ovulation

• Useful for couples with sexual dysfunction, discordance for STI carriage, unexplained infertility, mild endometriosis, mild male factor or for women undergoing treatment with donor sperm

• Minimum requirements:

- Ovulation in the IUI cycle

- At least 1 patent tube

- >1 million motile sperm

Intrauterine Insemination

• IUI more effective than timed intercourse (LBR, OR 1.95, 95% CI 1.10-3.44)

• Stimulated IUI more effective than natural cycle IUI (LBR, OR 0.48, 95% CI 0.29-0.82) ANZARD data 2013

Veltman-Verhulst et al, CL 2016