2015 women's health conference presentations

Public Funding for Fer0lity Dr Olivia Stuart Fer.lity Specialist

Initial Fertility Consultation

Fer.lity specialist • Public • Private

Private consultation option

• Pa.ents can self refer • Pa.ents can choose their fer.lity specialist • No mandatory tests required pre-‐referral • Fer.lity Associates’ specialists can see new pa.ents within 2 weeks in all our clinics

• consulta.on, scan, organise all their tests, assessed for public treatment, nurse

Public consultation • Condi.ons apply • Referring doctor needs to do a preliminary workup • Wait .me 3-‐4 months • Randomly allocated to one of 3 Auckland units, no choice

Eligibility criteria for public consultation

NZ residency Both partners must have • NZ residency, citizenship or • Work visa showing at > 2 years

Additional criteria for initial consultation

Work-up tests for initial consultation

Female Male

Day 2-3 FSH Oestradiol Semen analysis

Hepatitis B,C HIV syphilis rubella

Hepatitis B,C HIV

Blood Group FBC

Smear

Day 21 Progesterone

Publicly funded treatment

• Clinical Priority Access Criteria (CPAC) form • Criteria are the same across New Zealand • People need > 65 points using the fer.lity CPAC scoring tool • Score > 65 means eligible • All have same wait .me .l treatment

• The CPAC score can only be calculated by a fer5lity specialist.

> 65

CPAC Form

6

100

10

10 1

50

30

20

Couple A – Unexplained Infertility

6

80

10

10 1

40

30

10

Couple B – Male vasectomy

6

70

10

10 1

20

30

20

Couple C – Same sex couple

6

Waitlist for treatment

• The wait to treatment varies across the country • Generally 12–18 months • Pa.ents can access private fer.lity treatment whilst on the public wai.ng list

Second publicly funded packages

•  Requires rescoring •  All same eligibility criteria apply •  S.ll need CPAC score > 65 •  wait .me less •  Same unit

Treatment pathways to having a baby…

Couple Start Trying

See GP

First Appointment Public ($0)

Laparoscopy Public ($0)

Follow Up Public ($0) Need IVF

Funded Appointment FA ($0)

Funded IVF ($0)

12 Months 3 Months

6 Weeks

6 Weeks

6 Months

12 Months

•  Do everything Publicly Funded •  Total Cost $0 •  Total Time from GP to IVF – 24 months

All public…

Couple Start Trying

See GP

First Appointment FA ($270)


Funded IVF ($0)

Follow Up Private ($165) Need IVF

12 Months

6 Months

2 Weeks

2 Weeks

12 Months

•  1st Appointment in Private then Lap and IVF Public •  Total Cost $435 •  Total Time GP to IVF – 19 Months

Public and private 1…

Couple Start Trying

See GP




Private IVF ($10,000)

12 Months

6 Months

2 Weeks

4 weeks

2 Weeks

•  1st Appointment in Private then Lap in Public and IVF Private

•  Total Cost $10435 •  Total Time GP to IVF – 8 Months

Public and private 2…

Couple Start Trying

See GP


Laparoscopy Private (?Insurance)


Private IVF ($10,000)

12 Months

2 Weeks 2 Weeks

4 weeks

2 Weeks

•  1st Appointment in Private then Lap and IVF Private •  Total Cost $10435 +/-‐ Lap cost (insurance) •  Total Time GP to IVF – 10 weeks

All private…

On the horizon…

• Male smokers • Unexplained infer.lity for > 3 years in > 36 year old women

• BMI < 36

Ques0ons?

Infertility Diagnosis

When to refer? What’s New?

Dr Simon Kelly

Medical Director

Fertility Associates, Auckland

Look how far we have come?

The amazing story of IVF: 37 years

and 5 million babies later!

Infertility

Male

30%

Female

30%

Unexplained

25%

Combined

10%

Other

5%

• 1 in 7 couples

• Age single most important factor

When to refer?

• Trying for 12 months

• Ask about contraception

Infertility: (n)

A medical condition that diminishes self-esteem,

your social life as well as your checking and savings

accounts. Causes sudden urges to pee on sticks,

cry,scream and a fear of pregnancy announcements.

Treated by a Medical Specialist who you pay to

knock you up-this does not always work

Affects about 1 in 10 couples

Who to refer?

• Consider early referral if:

• >35yrs

• Irregular or absent periods

• Medical or surgical conditions that may affect fertility

eg endometriosis/pelvic surgery/chemo or radiotherapy

• Family history early menopause

• Recurrent miscarriage

• Genetic conditions amenable to PGD

• Patient Request

Free Nurse Consult - available for your patients

• 15 minute phone consult with a fertility nurse

• Answers questions like: • When to seek help • Treatment options • Costs • Public funding • Their % chance of having a baby

• Chinese speaking Free Nurse Consult now

available

Investigations • Male

• Semen Analysis

• Hep B/C/HIV

• Female

• FSH/Estradiol day 2-4cycle

• Thyroid function

• Rubella status/ Hep B/C HIV

• Prolactin if irreg cycles/galactorhoea

• HSG or HYCOSY if suspect tubal disease or previous PID*

• Ultrasound*

• AMH*

• Chlamydia swabs

• Check smear current

Advice- Improving Fertility

•Start Folic Acid and Iodine

•Minimize alcohol

•Reduce caffeine consumption

•Stop smoking

•Maintain ideal BMI (20-25)

•Improve diet

•Exercise

•Reduce Stress

New Diagnostic Tools

• AMH

– Currently best measure of ovarian reserve

– produced by small follicles as they grow on ovary

• Sperm DNA Fragmentation Testing

Sperm DNA Fragmentation Testing

• High levels DNA fragmentation may be

associated with:

– Poor fertility outcome

– miscarriage

• Causal Factors:

– Environmental / pollution exposure

– Advanced age

– Varicocoele

– Drug use

– Smoking

– Chronic Disease

Sperm Chromatin Structure Assay - SCSA

Sperm DNA Fragmentation

How do we treat?

-Antioxidants

-IMSI

-Surgical sperm

retrieval

Technologies

Matthew (Tex) VerMilyea, PhD, HCLD/CC Scientific Director

How to Choose the Best Embryo for Transfer?² Observational Analysis: Embryo Development Morphology Assessment

² Genomic Analysis: Trophectoderm Cell Biopsy

² Transcriptomic / Metabolomic Analysis:

Granulosa cells Cumulus cells Culture medium

TimeLapse Morphometry Imaging

TiMI Embryo Development

One frame at a time

t2: division to 2-cells t3: division to 3-cells t4: division to 4-cells t5: division to 5-cells t8: division to 8-cells

cc1: duration of first cell cycle (cc1 = t2-t1) cc2: duration of second cell cycle (cc2 = t3-t2) cc3: duration of third cell cycle (cc3 = t5-t3) s2: duration of transition from two-blastomere embryo to four-blastomere (s2 = t4-t3) s3: duration of transition from five-blastomere embryo to eight-blastomere (s3 = t8-t5)

Photos courtesy of Matthew (Tex) VerMilyea, PhD, HCLD/CCAdapted from Meseguer et al., 2011

1-cell 2-cells 4-cells 8-cells

t3 t2 t5 t4

cc1 cc2 cc3

t8

s2 s3

Discard?(Morphology)

Exclude?

t5

s2s2

cc2 cc2 cc2cc2

A+ A- C+ C-B+ B- D+ D- E F

ACCEPT DISCARD

INCLUDE EXCLUDE

WITHINRANGE

OUTSIDE RANGE

WITHINRANGE

OUTSIDE RANGE

WITHINRANGE

OUTSIDE RANGE

WITHINRANGE

OUTSIDE RANGE

WITHINRANGE

OUTSIDE RANGE

WITHINRANGE

WITHINRANGE

OUTSIDE RANGE

OUTSIDE RANGE

Clinical validation of embryo cultureand selection by morphokineticanalysis: a randomized, controlledtrial of the EmbryoScopeIrene Rubio, Ph.D.,a Arancha Gal!an, Ph.D.,a Zaloa Larreategui, Ph.D.,b Fernando Ayerdi, Ph.D.,b

Jose Bellver, M.D.,a Javier Herrero, Ph.D.,a and Marcos Meseguer, Ph.D.a

a Instituto Universitario IVI Valencia, University of Valencia, Valencia; and b IVI Bilbao, Bilbao, Spain

Objective: To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system (TMS) and selectionsupported by the use of a multivariable morphokinetic model improve reproductive outcomes in comparison with incubation in astandard incubator (SI) embryo culture and selection based exclusively on morphology.Design: Prospective, randomized, double-blinded, controlled study.Setting: University-affiliated private in vitro fertilization (IVF) clinic.Patient(s): Eight hundred forty-three infertile couples undergoing intracytoplasmic sperm injection (ICSI).Intervention(s): No patient intervention; embryos cultured in SI with development evaluated only by morphology (control group) andembryos cultured in TMS with embryo selection was based on a multivariable model (study group).Main Outcome Measure(s): Rates of embryo implantation, pregnancy, ongoing pregnancy (OPR), and early pregnancy loss.Result(s): Analyzing per treated cycle, the ongoing pregnancy rate was statistically significantly increased 51.4% (95% CI, 46.7–56.0)for the TMS group compared with 41.7% (95% CI, 36.9–46.5) for the SI group. For pregnancy rate, differences were not statisticallysignificant at 61.6% (95% CI, 56.9–66.0) versus 56.3% (95% CI, 51.4–61.0). The results per transfer were similar: statisticallysignificant differences in ongoing pregnancy rate of 54.5% (95% CI, 49.6–59.2) versus 45.3% (95% CI, 40.3–50.4) and notstatistically significant for pregnancy rate at 65.2% (95% CI, 60.6–69.8) versus 61.1% (95% CI, 56.2–66.1). Early pregnancy losswas statistically significantly decreased for the TMS group with 16.6% (95% CI, 12.6–21.4) versus 25.8% (95% CI, 20.6–31.9). Theimplantation rate was statistically significantly increased at 44.9% (95% CI, 41.4–48.4) versus 37.1% (95% CI, 33.6–40.7).Conclusion(s): The strategy of culturing and selecting embryos in the integrated EmbryoScope time-lapse monitoring system improvesreproductive outcomes.Clinical Trial Registration Number: NCT01549262. (Fertil Steril! 2014;102:1287–94. "2014by American Society for Reproductive Medicine.)Key Words: Early pregnancy loss, embryo culture, embryo selection, implantation, ongoingpregnancy rate, time-lapse

Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/rubioi-embryo-culture-selection-morphokinetic-analysis/

Use your smartphoneto scan this QR codeand connect to thediscussion forum forthis article now.*

* Download a free QR code scanner by searching for “QRscanner” in your smartphone’s app store or app marketplace.

I n recent years, clinical practice ef-forts have been directed towardimproving embryo selection. The

identification of embryos with a highercapacity for implantation means wecan reduce the number of embryos for

transfer without reducing the chancesof pregnancy in a cycle of assistedreproduction. To this end, differentnoninvasive embryo selection methodshave been designed that provide infor-mation on how to distinguish embryoswith better prognosis (1) There aredifferent methods of embryo gradation(2), but they are all based onmorphology, and evaluation ofmorphology under microscope is sub-ject to observer subjectivity (1). One ofthe noninvasive embryo evaluationmethods to have come into the lime-light in recent years is the time-lapse

Received January 17, 2014; revised and accepted July 9, 2014; published online September 11, 2014.I.R. has nothing to disclose. A.G. has nothing to disclose. Z.L. has nothing to disclose. F.A. has nothing

to disclose. J.B. has nothing to disclose. J.H. has nothing to disclose. M.M. has received paymentfor lectures from Ferring and Merck Serono.

The instrumentation, disposables, and utensils used in this study were fully paid for by IVI. IVI is aminor shareholder in UnisenseFertiliTech A/S, but none of the authors have any economicaffiliation with UnisenseFertiliTech A/S.

Reprint requests: Marcos Meseguer, Ph.D., Instituto Valenciano de Infertilidad, Plaza de la PolicíaLocal, 3, Valencia 46015, Spain (E-mail: [email protected]).

Fertility and Sterility® Vol. 102, No. 5, November 2014 0015-0282/$36.00Copyright ©2014 The Authors. Published by Elsevier Inc. on behalf of the American Society for Repro-

ductive Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

http://dx.doi.org/10.1016/j.fertnstert.2014.07.738

VOL. 102 NO. 5 / NOVEMBER 2014 1287

ORIGINAL ARTICLES: ASSISTED REPRODUCTION

•  Time-Lapse and multivariable morphokinetic classification tree improves outcomes compared to standard incubators and traditional morphology assessment.

•  Ongoing pregnancy rate increased from 41.7% to 51.4% (95% CI P-value .005)

•  Early pregnancy loss decreased from 25.8% to 16.6% (95% CI P-value .01)

•  Implantation rate increased from 37.1% to 44.9% (95% CI P-value .02)

ARTICLE

Computer-automated time-lapse analysisresults correlate with embryo implantationand clinical pregnancy: A blinded, multi-centre study

Matthew D VerMilyea a, Lei Tan b, Joshua T Anthony a, Joe Conaghan c,Kristen Ivani d, Marina Gvakharia e, Robert Boostanfar f, Valerie L Baker g,Vaishali Suraj b, Alice A Chen b, Monica Mainigi a, Christos Coutifaris a,Shehua Shen b,*

a Penn Fertility Care, University of Pennsylvania, 3701 Market St. Suite #800, Philadelphia, PA 19104, USA; b Auxogyn, Inc,1490 O’Brien Drive, Suite A, Menlo Park, CA 94025, USA; c Pacific Fertility Center, 55 Francisco Street, Fifth Floor, SanFrancisco, CA 94133, USA; d Reproductive Science Center of the Bay Area, 3160 Crow Canyon Road, San Ramon, CA 94583,USA; e Palo Alto Medical Foundation Fertility, Fertility Physicians of Northern California, 2581 Samaritan Drive, San Jose,CA 95124, USA; f HRC Fertility, 15503 Ventura Blvd, Suite 200, Encino, CA 91436, USA; g Stanford Fertility & ReproductiveMedicine Center, 900 Welch Road, Suite 350, Palo Alto, CA 94304, USA* Corresponding author. E-mail address: [email protected] (S Shen).

Matthew VerMilyea, PhD, HCLD, is Director of Assisted Reproductive Technologies and Andrology Laboratoriesat the University of Pennsylvania, USA, and Scientific Director of Fertility Associates, New Zealand. He gradu-ated from Cornell University, and received training in human embryology at Shady Grove Fertility, USA. Hethen obtained his PhD in Epigenetics from the University of Birmingham, UK. Matthew received a postdoctoralfellowship from the Japanese Society for the Promotion of Science for mammalian molecular embryologyresearch at the RIKEN Institute, Kobe. Research interests include non-invasive and uninterrupted embryoculture protocols, time-lapse video imagery, micro-environment culture settings and early embryo histonemodifications.

Abstract Computer-automated time-lapse analysis has been shown to improve embryo selection by providing quantitative and ob-jective information to supplement traditional morphology. In this multi-centre study, the relationship between such computer-derived outputs (High, Medium, Low scores), embryo implantation and clinical pregnancy were examined. Data were collected fromsix clinics, including 205 patients whose embryos were imaged by the EevaTM System. The Eeva scores were blinded and not consid-ered during embryo selection. Embryos with High and Medium scores had significantly higher implantation rates than those withLow scores (37% and 35% versus 15%; P < 0.0001; P = 0.0004). Similar trends in implantation rates were observed in different IVFcentres each using their own protocols. Further analysis revealed that patients with at least one High embryo transferred had sig-nificantly higher clinical pregnancy rates than those with only Low embryos transferred (51% versus 34%; P = 0.02), although pa-tients’ clinical characteristics across groups were comparable. These data, together with previous research and clinical studies, confirm

http://dx.doi.org/10.1016/j.rbmo.2014.09.0051472-6483/© 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Reproductive BioMedicine Online (2014) 29, 729–736

www.sciencedirect .comwww.rbmonl ine.com

37%(41/111)

23%(50/220)

0%

10%

20%

30%

40%

High Low

p = 0.003

Known Implantation

Eeva High

Eeva Low

Using a proprietary algorithm, images are automatically

analyzed

Multi-well Eeva™ Dish provides individual culture within the same media drop

Eeva System using /me lapse imaging and intelligent computer vision so6ware collects data inside a standard incubator

Eeva Test results provide objective information to assist embryo selection

PICSI & IMSIChoosing the best sperm

ICSI with PICSI• Washed sperm are tested to see what

proportion bind to a glass microscope slide covered with HA.

• If it is less than 65%, then washed sperm are added to a special Petri dish (PICSI dish) which contains a spot of HA.

• Sperm bound to the HA spot are removed and selected for use with ICSI.

Mature sperm bind to a substance called hyaluronic acid (HA) as they make their way through the cells protecting the egg in the human Fallopian tube. This is one of several mechanisms the body is known to use to select a good sperm to fertilise the egg.

PICSI may improve pregnancy rates and reduce the miscarriage rate. PICSI is suitable for:• Men having ICSI with at least

1 million sperm/ml in their ejaculate.• Men who have less than 65% HA

binding in the test (approximately 15% of men will be affected).

There are several ways to ensure that you are getting the best chance of pregnancy in IVF treatment. This fact sheet summarises the techniques available to help sperm selection in IVF-related treatment.

How to Choose the Best Sperm for Fertilisation?

•  Conventional IVF: ~100,000 sperm added to each egg

•  ICSI : Poor movement, number and shape

WHO ‘Normal Range’

Semen Volume 1.5 ml or more

Sperm Concentration 15 million /ml or more

Proportion of sperm motile 40% or more

Proportion with progressive motility

32% or more

Proportion of sperm with normal shape, using strict criteria

4% or more

Conventional In-Vitro Fertilisation

Intracytoplasmic Sperm Injection (ICSI)

Intracytoplasmic Morphologically selected Sperm Injection (IMSI)

x100 Magnification x600-6,000 Magnification

Intracytoplasmic Sperm Injection (ICSI)

embryos at the blastocyst stage were transferred into theuterus on day 5 by the TDT catheter set (CCD, Neuilly,France); if blastocysts did not develop, one or two morulawere transfered, whereas lower-cell embryos were nottransfered. Biochemical pregnancy was confirmed by thepositive serum b-hCG test (> 48 mIU/ml) 15 days afterthe embryo transfer, and clinical pregnancy by an ultra-sound scan of the gestational sac and the embryo heartbeats 14 days after the positive b-hCG test.

StatisticsTo evaluate the role of sperm selection by their morphol-ogy, the laboratory and clinical outcomes between theIMSI and ICSI groups of couples were compared. The

SPSS (Statistical Package for the Social Science; SPSS Inc.,Chicago, IL, USA) statistical program for MicrosoftWindows was used for statistical calculations. The labora-tory outcomes were expressed as fertilization rate (numberof fertilized oocytes per injected oocytes), number of blas-tocysts (%), number of blaststocysts per cycle, and numberof cycles with at least one blastocyst (%). The clinical out-comes were expressed as implantation rate (number ofimplanted embryos per transferred embryos), number ofpregnancies, pregnancy rate per cycle, and number ofspontanous abortions. For comparing categorical data, thechi-square (c2) test was performed, and Spearman’s rankcorrelation coefficient was used as a non-parametric mea-sure of statistical dependence between the two variables.

Figure 1 Classification of spermatozoa selected at 6,000 × magnification into 3 different categories. Class I - spermatozoa of goodquality, Class II - spermatozoa of worse quality, and Class III - spermatozoa of poor quality. Legend: a,b,c - spermatozoa of Class I; d,e,f -spermatozoa of Class II; g,h,i - spermatozoa of Class III.

Knez et al. Reproductive Biology and Endocrinology 2011, 9:123http://www.rbej.com/content/9/1/123

Page 4 of 8

•  Sperm do not have efficient DNA repair mechanisms.

•  Round vacuoles identified in sperm heads are associated with DNA fragmentation.

•  DNA damage caused by Reactive Oxygen Species (ROS) can be associated with age, temp, varicocele, smoking, diet, environmental toxins.

•  No implantation after >4 embryos transferred.

•  Poor embryo development from Day3.

•  Recurrent miscarriage from natural miscarriage.

•  Intracytoplasmic Morphologically selected Sperm Injection (IMSI) by Ultra-high magnification selection is available and can improve reproductive outcomes.

•  Fertility Associates is committed to providing the latest technology to our patients.

•  Time Lapse Morphometry Imaging (TiMI) service now available at FA which provides an uninterrupted growth environment and detailed assessment of embryological milestones.

Technologies

Matthew (Tex) VerMilyea, PhD, HCLD/CC Scientific Director

One Healthy Baby at a Time.

Thanks for the opportunity!

Fertility Preservation By Dr Mary Birdsall

Chair, Fertility Associates

Freezing Sperm

•60 years ago first human pregnancy from frozen sperm

•60 years ago first sperm bank

•Able to freeze low numbers

•Use insemination or ICSI

Who Should Freeze Sperm?

•Chemotherapy or radiotherapy or experimental medications

•Surgery eg prostatectomy or major pelvic surgery or orchidectomy

•Pre vasectomy or geographical challenges

•Pre gender reassignment surgery

•Sperm donors

•Klinefelters 47 XXY

Heterosexual couples Single women Lesbian couples

Donor Sperm

Freezing testicular sperm

• Unable to ejaculate

• Spinal injury

• Vasectomy

• Congenital bilateral absence of vas

• Azospermia

• Testicular cancer

Should young men freeze sperm for later?

•Sperm quality reduces with age

• Increase in schizophrenia, autism, achondroplasia with increasing paternal age

Prepubertal boys and fertility preservation

•No mature spermatogenesis

•Testicular tissue currently not being frozen

•No proven method to transform immature germ cells into functional sperm

• In mice: germ cell extraction, cryopreservation and re-injection with recovery of fertility

Spermatogenesis

Funding and the Law

•Pre cancer treatment sperm may be frozen free of charge

•Usual criteria for public funding for partners apply (woman less than 40, non smoker, BMI 19 to 32)

•May be stored for 10 years then must be discarded unless application for extension for storage made to ECART

Embryo Freezing

•First pregnancy - 1983

•Slow cooling

•Vitrification

•Need consent from both parties to thaw and use

•Who freezes embryos ?: surplus from IVF, pre chemo if have a partner and time, social, reduced ovarian reserve

RT

-6°C

-35°C

LN2

Equlibration

with

cryoprotectant

seedingSlow cooling rate

time

Equlibration

with

cryoprotectantRT

LN2

time

Slow cooling Vitrification Programmed equipment

Vitrification 2013

• 262 warming cycles • 289 embryos warmed (1.1 per cycle) • 279 embryos survived (96%) • 258 embryo replacement cycles (98%) • 115 pregnancies (44%)

Perinatal outcomes in Fresh IVF

cycles vs Frozen cycles

Frozen vs Fresh: antepartum haemorrhage

Frozen vs Fresh: SGA

Frozen vs Fresh: perinatal mortality

Fetal Abnormalities Frozen vs Fresh

•Reproductive Technologies and the Risk of Birth Defects M Davies et al NEJM 2012 366 1803-13

•South Australia population cohort study of more than 327,000 births

•Birth defects 8.3% after IVF vs 5.8% in spontaneous OR 1.47 (CI 1.33-1.62)

•No increased risk seen in frozen embryos

Summary Fresh IVF vs Frozen

•Frozen embryo cycles appear to have fewer obstetric and perinatal complications compared with fresh IVF cycles

•Suggests that ovarian stimulation may have a detrimental impact ? on endometrium

•So are frozen embryo pregnancy cycles comparable to spontaneous pregnancies?

Singletons after frozen transfer vs singletons after spontaneous conception

Outcome FET pregnancies Overall effect (RR, 95% CI)

Caesarean section 2947 1.76 (1.65 - 1.87)

Birthweight <2500g 2947 1.27 (1.05 – 1.52)

Birthweight <1500g 2787 1.51 (1.01 – 2.27)

Delivery at < 37 weeks 2947 1.39 (1.20 – 1.61)

Delivery at < 32 weeks 2947 1.45 (0.98 - 2.13)

Egg Freezing

Fertility preservation: cancer, social, religious or ethical objections to embryo freezing, no sperm at IVF, rapid reduction of ovarian reserve

•Vitrification

•Not funded $10,000

•3000 babies

Ovarian Tissue Cryopreservation

Ovarian Tissue Cryopreservation

•Oncological fertility preservation

•Only option for pre-pubescent girls

• Laparoscopy required

•Malignant cells being re-implanted a concern

•32 babies in world

•HRT

Ovarian cryopreservation in NZ

•46 ovarian tissue samples stored

•Permission to store but not yet an approved procedure

•2 pregnancies in Australia

Summary

• Men: can freeze sperm or testicular tissue

• Prepubertal boys: no options

• Couples: can freeze embryos

• Women: can freeze eggs or ovarian tissue or embryos with donor sperm

• Prepubertal girls: can freeze ovarian tissue

Questions from the floor

Babies, bones and body fat percentage Why worry about hypothalamic

amenorrhea?

Dr Megan Ogilvie

The Endocrine Group

Fertility Associates

Outline • What is Hypothalamic Amenorrhea? • Nomenclature

– Female athlete triad – IOC consensus statement – REDs

• How to diagnose – PCOS vs HA

• Why should we worry? – Bone Density – Future Fertility

• What can we do? – Multidisciplinary approach – Timing

Too Fat Too Thin or Just Right?

Kisspeptins

Ovary

Pituitary

Estrogen

Leptin

GnRH

FSH, LH

Energy Deficit

(Weight/ fat mass loss,

reduced nutrition, exercise)

Stress

(Physical or psychological)

Hypothalamus

Hypothalamic Amenorrhoea

Suppressed gonadotropin levels/function due to: chronic energy deficit and/or psychological stress

Lawson EA and Klibanski A (2008) Endocrine abnormalities in anorexia nervosa

IOC consensus Statement: RED-S • Energy deficiency

– Balance between energy intake and expenditure

– No standard method for assessing energy availability

• Specific sports at high risk – Runners, cyclists, jockeys, ballet

• Possibly effects males (need more studies)

– Lowered BMD

– Multisystem presentation, can be subtle (Br J Sports Med 2014;48:289)

Relative Energy Deficiency in Sport (RED-S)

Mountjoy et al, Br J Sports Med 2014;48:491–497.

Anna Smith • 25 year old woman

• Secondary amenorrhea 9 months

• Regular periods prior

• What will you ask her:

– No acne, hirsutism

– Busy lawyer – 60 hour weeks

– Recent relationship break up

– 7 hours/ week at gym, low carb diet, gluten free

– BMI 21, 5 kg weight loss 1 year ago

Polycystic ovarian syndrome vs hypothalamic amenorrhea

PCOS

– Periods weight

– Androgen excess symptoms

– Test, PRL, normal E2

– USS – normal endometrium

HA

– Periods weight

– Lanugo hair

– E2, LH, FSH

– USS – thin endometrium

– Spinal osteopenia

Don’t forget a mixed picture Robin, 2012

Assessment (What to Ask) Take your time with history – often the most informative

Aim is early diagnosis and intervention

Current BMI and pattern of weight change

Period pattern with weight change

Menarchal weight

Eating and exercise patterns - specifics

What else is going on - ?psychological stressors

Assessment (What to Measure)

Weight, BMI, waist circumference

LH, FSH and estradiol levels – FSH 5.4 LH 1 E2 <150

Prolactin, testosterone, TSH, pituitary testing

Venous bicarbonate if concerned about purging

Pelvic USS – thin endometrium

Bone Mineral Density

?Pituitary MRI

Diagnosis o Clinical history

o Less periods with energy deficit

o Psychological stressors

o Personality type – Type A, goal orientated

o Investigations

o Normal prolactin, TSH, T

o Low LH and oestradiol

o Thin endometrium

o Relative spinal bone loss THINK – hypothalamic amenorrhea

Why Worry? • Serious end points without intervention:

– Clinical eating disorders

– Osteoporosis

– Infertility

• Physical and emotional well being

– Decreased physical performance, injury rate

– Decreased cognitive performance

• Endothelial dysfunction due to low oestrogen

• High cortisol levels, low IGF1, low T

Effects on Bone • 90% of peak bone mass attained by 18 years

• Advantage of weight bearing exercise on bone lost in amenorrheic athletes

• Relative spinal BMD loss often seen

• Continued amenorrhea – 2-3% loss

bone mass/year

• OCP ineffective

• Transdermal oestrogen possibly

Effects on Fertility

• Infertility: anovulatory cycles and shortened luteal phase

• Reduced response to treatment: possible reduced pregnancy rates to IVF and increased miscarriage rate

• Adverse pregnancy outcomes: higher risks of pre-term birth and low birth weight

Prevalence of subtle menstrual disturbances among sedentary and exercising

volunteers

Assessed by daily hormone levels

De Souza M et al. Hum. Reprod. 2010;25:491-503

© The Author 2009. Published by Oxford University Press on behalf of the European Society of

Human Reproduction and Embryology. All rights reserved. For Permissions, please email:

[email protected]

A = sedentary women BMI 22.7 =/- 0.9 < 2 hr/week 100% regular periods

B = exercising women BMI 21.3 =/- 0.2 Purposeful exercise > 2 hr/week 7% oligomenorrheic 37% amenorrheic

Association between hours of vigorous physical activity per week and fecundability (BMI < 25)

Wise et al. Fertil Steril. 2012 May;97(5):1136-42.

Women age 18 – 40 yrs Self report of physical activity 12 month study Relationship preserved even when excluding women with BMI < 18.5

Lifestyle Management

Key to the reversal of all complications

Multidisciplinary approach:

– Specialist and GP – Sports physician – Nursing support – Dietician – Psychologist – CBT/hypnotherapy – Psychiatrist – Eating Disorder Unit (urgent: BMI<15.5, >4kg in

6/52, medical complications)

Lifestyle Management Need to find a reason relevant to the patient to

reverse

The art of negotiation

Adequate nutrition and maintenance of BMI within the ‘normal’ range (> 22)

Reduce exercise (at least 1 ‘rest day’ per week)

Minimise high impact exercise as much as possible

Keep addressing the anxiety caused by changes

It can take 9-12 months of stable weight before menstruation resumes

The weight needed for restoration of menses is typically higher than the weight at which menses was lost

Discuss body “burn out”

Warn that fertility may return quickly Monitor gonadotropins – LH increases first

Unclear why some respond quickly

– May be a genetic contribution

Take Home Messages Common diagnosis with the potential for

long term complications

Think about energy balance, not just BMI

Limit cardiovascular exercise fuel for exercise

Often multifactorial cause so discuss the issues and get support early (be alert to disordered eating)

Aim for a multidisciplinary approach

CBT and FHA • 20-week randomized trial CBT vs Ob

• 16 normal-weight women BMI 21-23

• < 10 hours exercise/week, no psychiatric diagnosis

• 16 CBT sessions – Healthy eating, exercise

– Problem solving and coping skills

– Body image

• Ovulation returned in 6/8 (CBT) vs 1/8(observation) BMI unchanged

Berga et al. Fertil Steril 2003;80:976-981.

Performance consequences of RED-S

Mountjoy et al, Br J Sports Med 2014;48:491–497.

The Female Athlete Triad

De Souza M J et al. Br J Sports Med 2014;48:289

Copyright © BMJ Publishing Group Ltd & British Association of Sport and Exercise Medicine. All rights reserved.

Ante Natal Screening An update about the latest screening

available in NZ including the new non-invasive prenatal diagnosis

Professor Peter Stone

Women’s Health Update

14 March 2015

SCOPE

• Antenatal(pre) natal screening-for what

• The role of the GP

• What is currently available

• Problems at present-how is the process performing?

• What is new -NIPT

• what does it mean for screening

• what is it used for

• what are the challenges

?

Are you interested in finding out about the

health of the baby?

We can be specific about what “health” means

NIPT is screening

The offer of prenatal screening

• An offer of prenatal screening provides prospective mothers the option of choosing or declining to receive (genetic) information pertinent to their personal situation prior to conception.

• After conception, prenatal screening-diagnosis provides various benefits: it determines the outcome of pregnancy and identifies possible complications that can arise during birth. It can be helpful in improving the outcome of pregnancy using fetal treatment. Screening can help couples determine whether to continue the pregnancy and prepares couples for the birth of a child with an abnormality

It is all about the offer- what is being offered and why

The role of the GP-primary carer

• At first chance- get involved!

• Lock in pregnancy care

• Be part of “life course” approach

~70% women have pregnancy confirmed by GP or FPC

Many opportunities to influence care are missed

There is evidence that most women-couples want screening There is also evidence that carers often prejudge woman’s approach to screening

% Women with LMCs by gestation and ethnicity

The question is

• What do you

want to know?

• What goes wrong

with babies-

And worries

parents

• Chromosomal

• Genetic-identified-known

De novo

Risk recurrence

• Structural

• Environmental-Infection

Epigenetic?

• Unknown-multiple abns

Cerebral palsy

Neurodevelop.delay

What goes “wrong” with babies Microdeletion syndromes

• DiGeorge 22q11 del

• Miller Dieker 17p13.3 del

• Prader Willi 15q11-13 del

• Smith Magenis 17p11.2 del

• Wolf Hirshhorn 4p16.3 del

• Williams-

Beuren 7q11.23 del

Nonsyndromic Microdel/dup

• 16p11.2 Autism

• 1q21.1 ID, microceph,cardiac cataracts

• 16p13.11 Austism, ID, schizophrenia

ID: Intellectual disability

Postnatally 15-20% by CMA vs 3% by G-band karyotype

T21 may be in the lexicon of many when they really are thinking of other problems

Some NIPT can do some of these

Perceptions T21 could be the lexicon for all this

Spectrum of disability

• Extra help at school

• Sequelae of prematurity-NICU

• ADHD

• Cerebral palsy

• Profound developmental delay-mental retardation

• Outcomes of structural fetal abnormality

What are the problems?

What are we trying to detect and avoid?

• Preeclampsia 3-5%

• Fetal growth restriction 5-10%

• Gestational diabetes 5+%

• Fetal abnormalities* 3%

• Risk of Preterm birth 2-7%

• Obstetric problems current pregnancy 5%

• Historical problems 5% Factors are additive and change risk eg obesity, hypertension, history

What we do now

• Current pathways

• Antenatal and newborn screening

history*-what are key questions?

Bloods, incl HIV,Chlamydia,smear as needed

Screening for Down Syndrome and other conditions

• Newborn metabolic and audiology

The current pathways and outcomes offer

1stT combined

Increased risk Low risk

No action Invasive diagnostic

outcome

+2ndT serum

Nt + 2nd T serum 1st and 2nd T serum

Low risk

62%

National Practitioner Guidelines

Laminated summary sheet

Most common chromosomal abnormalities

• Trisomy 21 (Downs Syndrome)

• Trisomy 18 (Edwards Syndrome)

• Trisomy 13 (Patau’s Syndrome)

• 45XO (Turners Syndrome)

• 47XXY (Klinefelters Syndrome)

• Triploidy 69xxx or 69xxy

• Mosaics/translocations/inversions

NIPT

Young women are less likely to be screened

and less likely to have a T1 screen

77.1

83.4

89.9 91.0 91.9 91.9

71.4

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

15-20 21-25 26-30 31-35 36-40 41-45 >45

0

5

10

15

20

25

30

35

Under 16 16–19 20–24 25–29 30–34 35–39 40 and over

% births

% Screens

Maori and Pacific peoples less likely to be

screened, less likely to have T1 screen

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

Māori Pacific

peoples

Asian European Other Not stated

% births

%screens

78.9

67.5

87.7

93.4

87.3 87.1

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

Māori Pacific

peoples

Asian European Other Not stated

Total screens 1st T screens

(of all screens done)

NZDep v relative amount of screening

R2 = 0.6647

0

20

40

60

80

100

120

140

4 4.5 5 5.5 6 6.5 7 7.5 8

Rich Poor

Ultrasound NT performance standards

Meet standard 22% Too few scans to analyse 40% Underperforming to 0.4mm 31% Unclassifiable 7% (nasal bone reporting very low-2 practices only)

Performance Issues in NZ

Detection rate 78% False pos rate ~3%

>100 sonographers < 25 NT scans /year

We are in a revolution

Non Invasive Prenatal Testing

THE LANCET Vol 350 • August 16, 1997 485

Presence of fetal DNA in maternal plasma and serum Y M Dennis Lo, Noemi Corbetta, Paul F Chamberlain, Vik Rai, Ian L Sargent, Christopher W G Redman, James S Wainscoat

http://www.google.co.nz/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&docid=OEABUz75YFdmvM&tbnid=KbgLCjHPsbajyM:&ved=0CAUQjRw&url=http://www.accessexcellence.org/AB/GG/structure.php&ei=LuqHU9fWFMLClAW6qYHICA&bvm=bv.67720277,d.dGI&psig=AFQjCNFJSbySLZ33O3rAimNwqK45dajWwg&ust=1401502622712275

Microarrays

3-4Mb

Single base change

Slide courtesy of Trent Burgess GHSV

Why is NIPT not diagnostic?

• Not only fetal DNA-placental as well

• It is a counting exercise with bioinformatics

and cut offs

• It needs diagnostic tests for confirmation

“Data obtained from a variety of clinical scenarios suggest that the placenta

is the predominant source of the circulating fetal nucleic acids,

although apoptotic haematopoietic cells may contribute to the pool as

well”. Bianchi DW Placenta 2004

53µ

m

73µm

Syncytial knots Or

Syncytial nuclear aggregates

Schmorl 1893

NIPT techniques

• Massively Parallel Sequencing

Fetal chromosome copy number determined by comparing number of sequence reads from chromos of interest to those from reference chromos

• SNPs targetted amplification and sequencing of SNPs

• Microarray based cf DNA analysis

DANSR- digital analysis of selected regions Juneau K et al Fetal Diag Ther 2014

Massively Parallel Sequencing Counting statistics Follow a normal distribution Cut off determines false positive rate 3SD above mean ~0.13% 4SD above mean ~0.003%

No

rmal

ised

ch

rom

oso

me

valu

es

Bianchi D Obstet Gynecol 2012

Factors affecting test performance Maternal Obesity Gestation Chromosome Biology Depth of sequencing Bioinformatics

Effect of Gestation and Maternal weight on fetal fraction

Dars et al 2014

Fetal Fraction- important

Chrom 21 Reference chromo

mat

ern

al

feta

l

Companies need to test and report this It affects the results

Low fetal fraction may occur in: Overweight Low PAPP-A and low bHCG T18 and T13

Performance

1stT Combined screening

• Detect rate 78-88%

• False neg >20%

• False pos 95%

• False pos rate 3-5%

• PPV (NZ) 8%

NIPT

• >99%

• <2%

• <2%

• <1%

• >80%

NIPT is very attractive as those positive-increased chance are highly likely to be a true positive on diagnostic-invasive testing And also fewer false negatives

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1:40

DOWN SYNDROME SCREENING APPROACH OBSERVED DETECTION RATES FOR 5% FALSE POSITVE RATES

Age 1960

Triple 1970

Quad 1990

Comb 2005

cfDNA 2012

OAPR 1:100 1:60 1:25 1:4 1:5

Int 2005

FPR 0.1% FPR ~3%

Current NZ performance

Meta analysis

• T21 DR99.2%(98.5-99.6) FPR0.09% (0.05-0.14)

• T18 DR 96.3%(94.3-97.9) FPR0.13%(0.07-0.20)

• T13 DR 91.0%(85.0-95.6) FPR 0.13%(0.05-0.26)

• X O DR 90.3%(85.7-94.2) FPR 0.23%(0.14-0.34)

• SCA DR93.0%(85.8-97.8) FPR 0.14% (0.06-0.24)

Ultrasound Obstet Gynecol 2015 DOI: 10.1002/uog.14791 Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis M. M. GIL, M. S. QUEZADA, R. REVELLO, R. AKOLEKAR, K. H. NICOLAIDES

Summary of NIPT- clinically realistic setting

• T21 DR 100% no false -ve

• Repeat testing 1.16% (Lau et al 2014)

• Non reportable-failure rate 0-4.9% (Benn P 2013)

• T18 DR~100%, T13 DR~91.% (Dan S 2012;Palomaki GE 2012)

Ultrasound Obstet Gynecol 2014; 43: 254–264Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single centerT. K. LAU, S. W. CHEUNG, P. S. S. LO, A. N. PURSLEY,M. K. CHAN, F. JIANG,H. ZHANG, W. WANG, L. F. J. JONG, O. K. C. YUEN, H. Y. C. CHAN, W. S. K. CHAN K. W. CHOY n=1982cases

Other examples of use of NIPT

• Fetal blood group genotyping* Targeted antenatal AntiD Determining surveillance in sensitised women • Fetal congenital adrenal hyperplasia • Cystic fibrosis • Spinal muscular atrophy etc * Available now

Some Companies • ARIOSA (US) «Harmony» (?array approach)

• VERINATA (US) «verifi» (Illumina)

• NATERA (US) «Panorama» (SNP approach)

• SEQUENOM (US) «MaterniT21»

• BGI (China) «NIFTY»

• LIFE-CODEXX (Germany) «PrenaTest»

Ask about fetal fraction, risk approach, failed test rate, what result is produced, coping with problems such as obesity, claims for twins- “expanded” screens and perhaps lastly cost

From 10 weeks 7 day turn around 21 18 13, ask doctor other SCAs Can do twins Cost-negotiate

basic verifi® Test screens for: T21 (Down syndrome) T18 (Edwards syndrome) T13 (Patau syndrome) Now a wider option is available for sex chromosomes at no extra charge: Monosomy X (MX; Turner syndrome) XXX (Triple X) XXY (Klinefelter syndrome) XYY (Jacobs syndrome) Fetal sex (XX or XY)—aids in stratifying the risk for X-linked disorders such as hemophilia, Duchenne muscular dystrophy, or cases of ambiguous genitalia, such as congenital adrenal hyperplasia

Verifir – by Illumina

http://www.ariosadx.com/

Panorama™ provides sensitivity >99% and positive predicted value (PPV) > 91% for Down syndrome. A microdeletion panel (including 22q11.2 deletion syndrome) is also available to provide unparalleled scope and reliability among non-invasive prenatal screens.

MATERNIT21® PLUS

22q deletion syndrome (DiGeorge) 5p (Cri-du-chat syndrome) 15q (Prader-Willi/Angelman syndromes) 1p36 deletion syndrome 4p (Wolf-Hirschhorn syndrome) 8q (Langer-Giedion syndrome) 11q (Jacobsen syndrome) Trisomy 16 Trisomy 22

From 10 weeks From 5 day turnaround Can expand Can do twins

Request form You do need to have counselled patient

and you do need to know

what you are requesting

MATERNIT21® PLUS

The clinician has to explain the results and discuss the limitations In practice, probably no difference from currently and for common trisomies Probably much more straightforward as the difference in likelihood of a true pos or neg result Is very wide compared with current tests ( eg 1:2chance of pos versus 1:1000 if negative)

Main difference is that clinicians are dealing with off shore companies and we have little idea of their QA and science We also take all responsibility for outcomes and it is no easy to “call up the lab”

The pathway and outcomes Current Pathway Future

offer

1stT combined


No action

Invasive diagnostic

outcome

offer

1stT combined

NIPT


No action

outcome

Invasive diagnostic

Risk cut off

A radical option?

Offer*

NIPT + scan**

Low risk

outcome

High risk

Invasive-amnio CVS

• *Be clear and simple what is the question? • **scan check list- no NT no part charge • Decide best timing of scan and ?do NIPT after

What might be missed-at this time

cfDNA may not detect:

• rare trisomies

• unbalanced structural rearrangements

• deletions and duplications

• triploidy

• marker chromosomes

• mosaicism.

Challenges

• Making a decision to do it- we have to

-it speaks for itself

• What are “the other conditions”?

- what trade offs - understanding we get what we ask for

- Where would NIPT fit infor all women or some?

• Costing the format

• Getting started in the Lab and validation

• Impact on invasives- skills of invasive operators

Cost- its not too bad actually

• Funded in Canada

• Insurance pays in USA

• UK study suggests can be cost neutral

(Morris S PLoS 2014)

• Costs vary with

Company

Techniques eg MPS vs SNPs

Volumes

Cutoffs in risk (if contingent)

What is screened for

No one costs false negs

Currently , on bulk contract could get for ~$250 NZ per test

Assumptions

Number screened now 45,000

Serum Costs

Serum 120

Scan 112

Total 232 $10,440,000

FPR 3% 1350

Invasives (75%) 1013@$1,000 $1013000

Missed cases 16 ?$$$

Total 11,453,000

NIPT Costs

NIPT 200

Scan 87

Total 287 12,915,000

False pos ~0.1

Invasives (80%) ~50 50,000

Missed cases 1-2

Total 12,965,000

Not included:

Capital costs to set up

Falling costs with volumes

Doing in a contingent way

Changed costs to patients eg cheaper scans less travel, less anxiety, fewer false pos and false negs

for trisomies

Identifiable costs Screening and invasives

Summary

• NIPT a great new advance- a new paradigm!!

• New era in performance

• Very low false pos and neg

• Much more reassuring for women

• Will further reduce invasive tests

• Provides a platform for the future- can change

• It is here now – lets do it well and ?offer to all

"I feel like the luckiest person alive," Dr Lee, a San Francisco-based anesthesiologist,

When she was 15 weeks pregnant, she underwent a whole-body MRI scan and a 7 cm tumor in the sigmoid colon was detected.

Medscape Medical News > Conference News Test for Fetal Abnormalities Finds Maternal Cancer Neil Osterweil March 06, 2015

With laparoscopic resection, the surgeons were able to completely remove the tumor. Postsurgical staging showed that it was T3N0M0 colon cancer

“The abnormalities seen are not diagnostic of cancer, Dr van den Boom explained. They could come from systemic lupus erythematosus, organ transplant rejection, or other causes, but test results in several cases have come back suggestive of various malignancies”.

As this expands do we need national and bioethical standards and controls?

http://www.medscape.com/news

http://www.medscape.com/index/section_3094_0

Click to edit Master title style

Click to edit Master subtitle style

1 3/17/2015 1 3/17/2015 1

Breast Cancer Update

Wayne Jones FRACS



2 3/17/2015 2


2 3/17/2015 2

Topics

• Breast Imaging

• Breast Surgery

• Adjuvant Treatment



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3 3/17/2015 3

Breast Imaging

• Digital mammography

• Tomosynthesis mammography

• Office ultrasound

• Image guided biopsies

• MRI − High risk screening & specific questions

− ? Lobular Ca & DCIS

− Cost, claustrophobia, over-calls cancer



4 3/17/2015 4


4 3/17/2015 4

Digital Mammography



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5 3/17/2015 5

Digital Mammography



6 3/17/2015 6

Tomosynthesis Mammography



7 3/17/2015 7

Office Ultrasound



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8 3/17/2015 8

U/S Guided Core Biopsy



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9 3/17/2015 9

Breast MRI



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Breast Surgery



11 3/17/2015 11

Mastectomy



12 3/17/2015 12

Breast Conservation Surgery



13 3/17/2015 13

Breast Conservation Surgery



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Sentinel Node Biopsy

• 40% lymph node involvement

• U/S and FNA biopsy

• Pre-op ID of sentinel node 95%+

• Smaller operation, less morbidity eg shoulder pain, lymphoedema

• No difference in DFS or OS v AND

Nodal Basin

Tumour



15 3/17/2015 15

Lymphoscintogram



16 3/17/2015 16

Patent Blue V Dye



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Hand-held Gamma Probe



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Hand-held Gamma Probe



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Is Axillary Dissection Needed?

• Currently if − SNB positive have ALND

− SNB negative avoid ALND

• Isolated tumour cells <0.2mm – not significant

• Micrometastases <2mm – increased LR, ? ALND

• Micrometastases >2mm – Do ALND

• If 3 or more nodes involved omit ALND if getting

systemic tx and DXR (Z-0011 trial, IBCSG 23-01)



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20 3/17/2015 20

Breast Reconstruction

• Offered to all ‘Mastectomy Patients’

• Psycho-social & sexuality reasons

• Immediate or Delayed

• Implants – one or two stage

• TRAM flaps - muscle, fat & skin

• DIEP flaps – fat & skin, microvascular



21 3/17/2015 21


21 3/17/2015 21

Permanent Implants



22 3/17/2015 22

How strong are they?



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One Stage Implant



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24 3/17/2015 24

Two Stage Implant – Pre-op



25 3/17/2015 25


25 3/17/2015 25

Two Stage Implants



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26 3/17/2015 26

Two Stage Implant - Expansion



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27 3/17/2015 27

Two Stage Implant – Post-op



28 3/17/2015 28


28 3/17/2015 28

TRAM Flap



29 3/17/2015 29


29 3/17/2015 29

Delayed TRAM flap



30 3/17/2015 30

Nipple Reconstruction



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Nipple Reconstruction



32 3/17/2015 32


32 3/17/2015 32

Nipple Sparing Mastectomy

• No increased risk breast cancer if preserve nipple − If >2cm from nipple, not multifocal

− Frozen Section at surgery

• Routine for prophylatic mastectomies

• Selected cancer mastectomies − Not contra-indicated as above

− Can preserve blood supply

• Inferolateral approach or peri-areola



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33 3/17/2015 33

Nipple Sparing Mastectomy



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Adjuvant Treatment



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Radiotherapy

• All cases of Partial Mastectomy for DXR

• Nodal status important − Was >3 nodes, now 1 node treated (EBCTG 2014)

• Intra-operative DXR − Controversial

− Some patients don’t need DXR at all

− Editorial Int J Rad Onc 2015 91(2), p255-7

• Partial breast irradiation



36 3/17/2015 36

Endocrine Therapy

• Aromatase Inhibitors more effective than Tamoxifen − 17% less recurrence, 53% less contralateral cancer

− Less DVT, Hot flushes, uterine Ca, more joint pain, lose bone density

• Can switch to AI after 2y

• Duration – 10y better than 5y

• Primary endocrine therapy if unfit for surgery

• Pre-menopausal women − Use Exemestane & Zoladex (GnRH inhibitor)

− More effective than Tamoxifen (SOFT trial)



37 3/17/2015 37

Chemotherapy

• More effective 3rd generation chemo

• Use of multi-agents

eg AC & Taxol, FEC & Taxol

• Tailor treatment eg basal type, gene array analysis

• Neo-adjuvant tx for Her2 +ve & “triple negative”

• Management of Her2 +ve Ca <1cm controversial

• Consider fertility treatment



38 3/17/2015 38

Herceptin (Trastuzumab)

• 20% women HER2 +ve

• HERA Study – recurrence ↓46%

• 12m course $80,000

• Give with chemo

• 3m versus 12m?

• Combination with Pertuzumab?

• Need Portacath



39 3/17/2015 39



40 3/17/2015 40 3/17/2015 40

Questions?

2015 women's health conference presentations

Documents