Accessible infertility care - From dream to reality:first pregnancies with a simplified IVF procedure

Willem OmbeletGenk, Belgium

1st congressMale infertility750 participants34 countries

34 yearsIVF

> 5.4 million IVF / ICSI babies worldwide

SUCCESS ???

Robert Edwards2010 Nobel Prize winner

Howard Jones, US IVF pioneer

www.nightearth.com

5www.ivf-worldwide.com/ivf-directory/ www.nightearth.com

But what about …

Developing Countries

=overpopulation

More important priorities:HIV, tbc, malaria, vaccinations …

1st priority =

PreventionEducation

Family-planning

ART = expensive

Limited ResourcesArgument

ART = ethical issue

Limited budget

Limited or no interest for infertility in developing countries

Infection-related tubal blockAsia

Latin America Africa

39 %

44 %65 - 85 %

Tubal factor : why ?

Sexually transmitted diseases Post-partum infections Illegal abortions Urbanisation - mobility Polygamy Resistant micro-organisms …

1.“Men and woman of full age, without any limitation due to race, nationality or religion, have the right to marry and to raise a family”. This statement was adopted 60 years ago at the 1948 UN Universal Declaration of Human Rights and can’t be misunderstood: it implies the right to access to fertility treatments when couples are unable to have children.

2. At the United Nations International Conference on Population and Development in Cairo in 1994 the following statement was made “Reproductive health therefore implies that people have the capability to reproduce and the freedom to decide if, when and how often to do so … and to have the information and the means to do so …”

3. UN Millennium Declaration, signed in September 2000 : “Achieve, by 2015, universal access to reproductive health”.

4. In 2001, on the occasion of a WHO meeting on "Medical, Ethical and Social Aspects of Assisted Reproduction" in Geneva, a call for the integration of infertility into existing sexual and reproductive health care programmes in developing countries was made.

5. In 2004 the World Health Assembly proposed five core statements, including “the provision of high-quality services for family-planning, including infertility services”.

World community statements

• Infertility not very prevalent in

developing countries

• Infertility is not a serious problem for people in developing

countries

• “Individual problem, not a public health problem, not a

problem of the nation…”

Why should we care ?

Prevalence of infertilityPrevalence of infertility

mill

ions

mill

ions

(Source:(Source: Rutstein and Shah, Rutstein and Shah, DHS Comparative ReportsDHS Comparative Reports, no. 9, no. 9, ,

2004)2004)

Total: 186 million women

The estimate of the magnitude of the involuntary infertileDemographic definition - 5 years of childlessness (2004) (in developing countries minus China, data up to year 2000)

18

168

Primary infertile Secundary infertile

mill

ions

180

160

140

120

100

80

60

40

20

0

• Infertility not very prevalent in developing countries

• Infertility is not a serious problem for

people in developing countries

• “Individual problem, not a public health problem, not a

problem of the nation…”

Why should we care ?

WHO Current Practices and Controversies in Assisted Reproduction "Infertility and social suffering," Daar & Merali, 2001, page 18, Figure 2.

Developing/ transitional societies

Developed societies

Challenge: address infertility as an impairment of body function which is affected by societal features

Level 6

Level 5

Level 4

Level 3

Level 2

Level 1 Fear, guilt, self-blame

Marital statusDepression, helplessness

Mild marital / social violenceSocial isolation

Severe economic deprivationModerate / severe violenceTotal loss social status

Violence-induced suicideStarvation / disease

Lost dignity in death

• Transactional sex• Concurrent partners

• Multiple unions• No condom use

• Early age at first sex• Gender based violence

• Transactional sex• Concurrent partners

• Multiple unions• No condom use

• Early age at first sex• Gender based violence

unintended

pregnancies

(unsafe abortions)

unintended

pregnancies

(unsafe abortions)

INFERTILITY AND

CHILDLESSNESS

INFERTILITY AND

CHILDLESSNESS

Poverty, low education, gender inequality, high value of children, limited health care

Bad sexual health,

obstetric and

neonatal care

Bad sexual health,

obstetric and

neonatal care

STIs/HIV

• Infertility not very prevalent in developing countries

• Infertility is not a serious problem for people in developing countries

• “Individual problem, not a public health problem, not a problem of the nation…”

Why should we care ?

Mother or nothing – the agony of infertilityProf dr M Fathalla, WHO Bulletin, December 2010

“In a world that needs vigorous control of population growth, concerns about infertility may seem odd, but the adoption of a small family norm makes the issue of involuntary infertility more pressing. If couples are urged to postpone or widely space pregnancies, it is imperative that they should be helped to achieve pregnancy when they so decide, in the more limited time they will have available.”

How to prevent suffering?

→ accept pronatalism and try to help people to have children→ fight pronatalism : reduce the negative socio-cultural and

economic consequences of infertility

Best solution → combination of both strategies on the basis of cost-effectiveness

Pennings, 2010

Social and psychological suffering

International organisations: no International organisations: no interestinterest

International Planned Parenthood Federation◦ Only family planning research and HIV prevention

The Population Council◦ Leading role in development new contraceptives

Family Planning International◦ Focus on family planning research and HIV

prevention

World Health Organization◦ Focus on family planning & prevention STD’s // HIV

One-day clinic(diagnosis)

Ovarian stimulation for IVF

IVFLaboratory

Make itMake it

SIMPLESIMPLEEFFICIENTEFFICIENT

SAFESAFEAFFORDABLEAFFORDABLE

Arusha (expert) meetingDecember 15-17, 2007

Convincing the scientific community

Health Care Centres

Family planningMother care

Infertility care

Holistic model of reproductive healthcare horizontal and infertility included

Make it

SIMPLEEFFICIENT

SAFEAFFORDABLE

IVF laboratory

One day clinic (diagnosis)

IVF ovarian stimulation

Arusha meeting 2007

HIGH COST IVF LabExpected price

→1.5 - 3 Million €

t WE lab - a simplified IVF procedure

Simplified Culturing System

Two glass tubes connected by needles and tubing

tube 1 = CO2 generator

Citric acid + sodium bicarbonate -> CO2

tube 2 = medium equilibration / IVF

Fertilisation and culturing in separate glass tubes

CO2 incubator not neededProf. Dr. Jonathan van BlerkomUniversity of Colorado, Denver

Prof. Dr. Willem Ombelet and Prof. Dr. Carin Huyser

Step 1: Set-up and equilibration

Citric acid + sodium bicarbonate + water

produces carbondioxide to equilibrate

culture medium to pH 7.25- 7.35

6.3 - 7.1 % CO2

12 - 13% O2

Step 1: Set-up and equilibration

Step 2: Insemination

QuickTime™ en een-decompressor

zijn vereist om deze afbeelding weer te geven.

Insertion of oocytes and sperm cells: 1 oocyte per

tube with 1000-5000 good motile sperm cells

Day 0

QuickTime™ en een-decompressor

zijn vereist om deze afbeelding weer te geven.

Step 3: Fertilisation check

Fertilisation check through

the glass tube wall

Day 1

Step 4: Embryo visualisation

Day 2 Day 3

Embryo transfer

Day 2 Day 3

Couple selected for first IVF trial ♀ < 36 years

♂ IMC> 1 million

Ovarium Stimulation(Rec FSH-antagonist)

Oocyte retrieval (OR)

IMC < 1 mill

< 8 oocytes

Regular culturing

SET

Regular Culturing (RC) Simplified Culturing (SC)

If 1 top embryo

If ≥ 2 top embryos

1st TRIALIf no top embryo

If no fertilisationIf no good quality embryo

No transferExcluded

SET day 3

SET: RC embryo

SET: SC embryo

Serum HCG 9 – 11 days after OR

Negative Positive

Randomisation

Excluded

ICSI

++

Cryo surplus embryos

≥ 8 oocytes

Ultrasound 5-6 weeks after OR

Interim report

Age < 36yrs, min 8 oocytes, SET

17/28 t WE lab (60,7%) 11/28 RCS (39,3%)ET

HCG+ 7/17 t WE lab (41,2%) 2/11 RCS (18,2%)

IR 6/17 t WE lab (35,3%) 2/11 RCS (18,2%)

1 BC

FR t WE lab : 60.8%

FR SCS: 58.2%

n= 28

first pregnancy from Frozen ET

4 excluded

Day 3

Until 31-12-12

12 ongoing pregnancies

First delivery 07-11-12 – healthy boy – 3500 gr

Simplified culturing system

Day 3

t WE lab - a simplified IVF procedure

Direct costs IVF Laboratory

10 – 15 %

Cost per IVF cycle (medication excluded)2500 € → < 200 €

Laboratory Fees35%

Doctor Fees29%

Clinic Fees8%

Medication28%

Laboratory Fees48%

Doctor Fees23%

Clinic Fees6%

Medication23%

Cost analysis per procedure in a private practice in South Africa

C Huyser 2012

IVF

ICSI

3 9

D1

4 5 6 7 8 X Day 0

US OVARIESPick-up

hCG 5000 UClomiphene 100 mg

MENSES

>= 17 mm

35 h

Modified IVF protocol

Day 3

US OVARIES ET

PriceMedication

25 - 120 Euro

PriceMedicationBelgium per

cycle1075 Euro !!

Menopur 75 or Puregon 75Low dose hCG

• Studies with low stimulation protocols (CC-low dose hCG) in t WE lab setting

• Studies on sperm number needed for IVF in t WE lab setting

• Cost – analysis …

Current / future developments

tWE IVF centre

tWE training centre

Solar energy 2013

Compton Foundation

http://nnadofoundation.webs.com/

What about funding ??

www.thewalkingegg.com

Nairobi

Pretoria

Lima

Mumbai

NumberedSigned

Registrated

When a thing was new, people said,“It is not true“

Later when the truth became obvious, people said,“Anyway, it is not important“

And when its importance could not be denied, people said,

“Anyway, it is not new“

William James, 1842 - 1910