IN VITRO FERTILIZATION AND LONGEVITY KOSTAS PANTOS · 2017. 9. 8. · •Oocyte donation was early...

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KOSTAS PANTOS Obstetrician-Gynecologist, PhD Head of IVF UNIT, Genesis-Athens Clinic, Greece IN VITRO FERTILIZATION AND LONGEVITY

Transcript of IN VITRO FERTILIZATION AND LONGEVITY KOSTAS PANTOS · 2017. 9. 8. · •Oocyte donation was early...

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KOSTAS PANTOS Obstetrician-Gynecologist, PhD

Head of IVF UNIT, Genesis-Athens Clinic, Greece

IN VITRO FERTILIZATION

AND LONGEVITY

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In the sacrament of marriage, the absolute union in body and soul,

in Christ’s love, between man and woman, the childbearing arises

as the great purpose and splendid, according to the Divine Law.

1st Rel. Annex Sec. 11th , pg. 702, V.Moustakis et al.

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The God most pure, Author of all creation, Who through Your

manbefriending love transformed a rib of Adam the forefather

into a woman, and blessed them and said, "Increase and

multiply, and have dominion over the earth”, and, by the

conjoining … and the two shall be one flesh-and whom God …

Who did also bless Your servant Abraham, and opened the

womb of Sara, and made him the father of many nations;

Wishes of Church for childbearing: Wedding Wish

Holy Matrimony - The Service of Betrothal

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Among God's promise to Abraham one was that of having a

child, though he had reached the age of 100 years old and

Sarah the age of 90.

Having child at old age in the Old Testament

Old Testament, Genesis 18: 11,12, 14, 15, 18,19

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As Adam the first progenitor of mankind was blessed by God, (Gen. Ch. 1:28-30) to the

same way God blessed Noah as the new progenitor of mankind.

The blessing is threefold:

The first part concerns the proliferation of people, the domination over the animals

and the food.

Next the Testament of God follows (Gen. Ch.1: 8-17), that He will not Bring about

cataclysm again and the Rainbow will be the symbol and sign of God’s promise.

The third part of the Testament (Ch. 9: 18-29) is the rest of Noah's life, which lasted

here on Earth 350 years and promises in relation to his sons Shem, Ham, and Japheth.

Correlation of Longevity in the Old Testament

Old Testament, Genesis 1

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Reproduction later in life is a marker for longevity in womenBoston University Medical Center, ScienceDaily, 25 June 2014

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• Women who are able to naturally have children later in life tend to live longer and the

genetic variants that allow them to do so might also facilitate exceptionally long life spans.

• A Boston University School of Medicine (BUSM) study published in Menopause: The Journal

of the North American Menopause Society, says women who are able to have children after

the age of 33 have a greater chance of living longer than women who had their last child

before the age of 30.

• "Of course this does not mean women should wait to have children at older ages in order to

improve their own chances of living longer. The age at last childbirth can be a rate of aging

indicator. The natural ability to have a child at an older age likely indicates that a woman's

reproductive system is aging slowly, and therefore so is the rest of her body."

Thomas Perls, MD, MPH, Director of the New England Centenarian Study (NECS)

Reproduction later in life is a marker for longevity in women

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• The study was based on analysis of data from the Long Life Family Study (LLFS)-a biopsychosocial and

genetic study of 551 families with many members living to exceptionally old ages.

• The study investigators determined the ages at which 462 women had their last child and how old those

women lived to be.

• The research found that women who had their last child after the age of 33 years had twice the odds of

living to 95 years or older compared with women who had their last child by age 30.

• The NECS found that women who gave birth to a child after the age of 40 were four times more likely to

live to 100 than women who had their last child at a younger age.

Boston Medical Center - LLFS

Boston University School of Medicine (BUSM), Menopause: The Journal of the North American Menopause Society

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AGING

Older Moms May Live LongerAlice Park Nov 17, 2016 TIME Health

http://time.com/4574770/older-moms-may-live-longer/

TIME Health

• Α multi-year study οf the nearly 28,000 post-menopausal women in the U.S., found that around half survived to reach age 90, and researchers showed that delaying childbirth is associated with longer life.

• Compared to women who weren't yet 25 when they first gave birth, women who were older than 25 were 11% more likely to live to 90.

American Journal of Public Health: “Our study is the first to look at age at first childbirth and parity [number of children] in relation to survival to very advanced age.”

• Τhe women who had two to four children were generally healthier overall than women who had one child.

• WHI studies suggest that women who have children later and live longer are also healthier as they age.

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Old Order Amish Community in Lancaster, Pennsylvania, “Homogeneous Lifestyle”

Does the act of having a child make people live longer?

• Lifestyle has the avoiding of riskier habits.

• Offspring responsibility by taking care of their children.

• It is quite likely childless couples engage in riskier activities than women who

do not participate in these activities at all.

• Men and women with children tend to take better care of themselves.

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• Breastfeeding an infant has been repeatedly found to reduce the risk of

certain cancers. This is probably due to the temporary suppression of

production of estrogen.

• Fetus can release stem cells into their mother's blood circulation that act as

generic healing agents.

• Pregnant women tend to heal faster than non-pregnant ones. Maybe each

pregnancy "heals" the mother to some extent, conferring longer lifespan.

Legitimate health benefits associated with the actual process of bearing children

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• A study published in 2013 suggests that women who can't have children have a

shorter life expectancy than women who do not bear children, but the author

admits that this could partially be due to those childless women having other

health problems that caused their infertility: Though correlation found is not

necessarily a cause-and-effect relationship.(Agerbo, E. J Epidemiol Community Health 2013;67:374-376)

• There are also studies that show that women with more children live longer than

women with few children.(Simons et al. Age Ageing 2012;41:523-528)

Is there a difference in life expectancy between women who have children and infertile women?

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The relationship between fertility and lifespan in humansMaris Kuningas, Signe Altmäe. André G. Uitterlinden, Albert Hofman, Cornelia M. van Duijn, Henning Tiemeier, AGE (2011) 33:615–622

Fertility has also been associated with mortality. Women with

two to three children had significantly lower mortality (hazard

ratio (HR), 0.82; 95% confidence interval (95% CI), 0.69–0.97)

compared to women with no children.

True association of mortality vs fertility ?

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• Women with children tended to have their menopause at later ages

than women without children.

• Women who have their menopause at later ages have decreased

risk of having a heart attack, stroke, or other cardiovascular

disease event, but increased risk of having breast or endometrial

cancer.

Hu et al. 1999; Sowers and La Pietra 1995

Or observational phenomenon ?

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Birth rates USA 1990-2012

Birth rates by selected age of the mother: United States, 1990–2012

Source: CDC/Eunice Kennedy Shriver National Institute of Child Health and Human

Development, National Vital Statistics System.

Sauer. Reproduction at advanced maternal age. Fertil Steril 2015

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Birth rates by selected age of the mother

LANDMARK PAPERS:

Sauer et al., A preliminary report on oocyte donation extending reproductive potential to women over 40. N Engl

J Med 1990;323: 1157–60.

Sauer et al., Pregnancy after age 50: application of oocyte donation to women after natural menopause. Lancet

1993;341: 321–3

Pantos et al., Oocyte donation in menopausal women aged over 40 years. Hum Reprod. 1993 Mar;8(3):488-91

Birth rates by selected age of the mother: United States, 1990–2012

Source: CDC/Eunice Kennedy Shriver National Institute of Child Health and Human Development,

National Vital Statistics System Sauer. Reproduction at advanced maternal age. Fertil Steril 2015

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NATURAL FERTILITY DECLINE WITH AGE

THE RELATIVE EFFECT

OF AGE ON FECUNDITY

THROUGH IVF

2011 SART data, 6/2/2013

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CURRENT FEMALE REPRODUCTIVE ATTITUDES

BIOLOGICAL REALITY:

•Menopause, the loss of ovarian function,

occurs between ages of 45-55 and lasts

>9-12 months and is considered inevitable

TODAY’s CHALLENGE

•Identify perimenopausal period

•Offer realistic options in child bearing

SOCIETAL ACCEPTANCE IN DELAYED PARENTHOOD:

•Personal autonomy in decision making

•Educational goals, career pathways, ambitions

•Finding the ‘proper’ life partner

•Successful women and denial of biological reality

•Role of Reproductive Technologies in resolving reproduction issues

•Favorable reporting bias of the mass media of ‘menopausal mothers’

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Pre-Conceptional counseling for AMA

Identify peri-menopausal period

•Age

Determine ovarian reserve with Known potential markers:

•AMH (Anti-Müllerian hormone) levels

•AFC (antral follicle count) as measured

by transvaginal ultrasound1-4.

•Basal FSH levels

•Basal E2 levels

•Inhibin B

1. Broekmans et al. Menopause. 2004;11:607-14

2. Dólleman et al. Hum Reprod. 2015;30:1974-81

3. Broer et al. J Clin End Metab. 2011;96:2532-9

4. Wellons et al. Menopause. 2013;20:825-30

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PERIMENOPAUSAL CONCEPTION

“TIME IS OF THE ESSENCE”

•Natural conception

•IVF treatment

•Oocyte donation

•Oocyte or ovarian tissue cryopreservation

•OVARIAN REJUVENATION (RECENT)

•True preventive approach (best)

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IVF TREATMENT OF PERIMENOPAUSAL WOMEN

• Perimenopausal women often characterized by poor response to controlled ovarian

stimulation1 and increased probability of IVF cycle cancellation due to the

retrieval of inferior quality oocytes4

• Embryo transfer after prolonged embryo culture to blastocyst stage4

• Double same cycle follicular and luteal phase mild stimulation protocols,

cryopreservation, ET in thaw had increased pregnancy rates2

• AMH-tailored stimulation protocols claim to improve pregnancy rates for women

in advanced maternal age3

• Live birth rates in perimenopausal women decline as maternal age increases4

1. Marcus et al. Hum Reprod Update. 1996;2:459-68 3.Chi-Chun et al. Taiwan Journal of OB/GYN 55(2016)239-243

2. Yanping et al. Reprod BioMed Online 2014;684-691 4. Gleicher et al. Journal of Endocrinology 2016;230,F1-F2

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PERIMENOPAUSAL WOMEN & NATURAL IVF

• Studies show live birth rates significantly higher in modified natural cycles

compared to high-dose FSH & GnRH antagonist cycles1

• Other studies show natural cycle IVF only indicated for normal responders, while

poor ovarian responders do not appear to experience substantial benefits2

• As peri-menopausal women are usually characterized by poor ovarian response to

standard gonadotrophin stimulation, natural cycle IVF +/- embryo banking from

consecutive cycles +/- PGS could be a promising therapeutic option 4,5

• Reports of premature luteinization in older women suggest giving hCG trigger

earlier at lead follicle 16mm3

• Androgen supplementation(DHEA) still controversial3

1. Lainas et al. Hum Reprod. 2015; 30:2321-30–1547 2

2. Polyzos et al. Hum Reprod. 2012;27:3481–86

3. Gleicher et al. Journal of Endocrinology (2016) 230,F1-F6

3. Lawson et al. Hum Reprod. 2003;18:527-33

4. de Boer et al. Fertil Steril. 2002;77:978-85

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PERIMENOPAUSAL WOMEN & OOCYTE DONATION

• Oocyte donation was early stratified in the IVF treatment of peri-menopausal1 and

post-menopausal2 women with successful results even in advanced maternal ages

(63 years)2,3

• The success of oocyte donation/recipient cycles depends on donor's age4. Namely,

if oocytes are donated by young women to older women, both embryo implantation

and pregnancy rates are restored to normal levels in the recipients, regardless of

their age 4

• Given that the cumulative birth rates after four donation/recipient cycles is >80%,

oocyte donation seems to be the most reliable option for perimenopausal woman3,5

1. Sauer et al. Am J Obstet Gynecol. 1990;163:1421–4 4. Pantos K et al. Hum Reprod. 1993;3:488-91

2. Antinori et al. Hum Reprod. 1993;8:1487–90 5. Sauer et al. J Assist Reprod Genet. 1994:11:92–96

3. Paulson et al. Hum Reprod. 1997;12:835–839

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What is already known:

• Platelet-rich plasma (PRP) emerges amongst the most innovative autologous

blood products used to enhance tissue healing and regeneration

• Platelets carry more than 800 proteins, such as cytokines, hormones and

chemo-attractants of stem cells, macrophages and neutrophils, responsible

for various post-translational modifications of nearly 1,500 bioactive factors

• Platelets carry various growth factors, which are released after alpha granule

activation

• Secreted active proteins are then bound to transmembrane receptors of target

cells, causing expression of a gene sequence that directs various events, e.g.

proliferation, collagen synthesis

• Active secretion within 10 min after activation, with more than 95% of the

pre-synthesized growth factors secreted within 1 h

Platelet-rich plasma (PRP)

Dhilllon et al.Arthritis Res Ther 2012;14:219, Qureshi et al. PLoS One 2009;4:e7627,

Mussano et al, Platelets,2016 Early Online: 1–5

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PRP treatment in medicine

• Bone regeneration

• Osteoarthitis

• Nerve injury

• Tendinitis

• Myocardial infraction

• Alopecia

• Ocular surface disease

• Skin rejuvenation

• Wound healing and fat grafting

1.Yu et al., 2011 2. Mishra et al., 2009 3. Li et al., 2008 4. Khatu et al., 2014

5. Alio et al., 2012 6. Yuksel et al., 2013 7. Sommeling et al., 2013

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• Reports of fibrosis and inflammation as hallmarks of aging ovary1

• PRP treatment reported to cause angiogenesis activation, inflammation control,

anabolism increase, cell migration, differentiation and proliferation, plus reverses

apoptosis 2,3

• The study of an ischemia/reperfusion injury rat model has shown that PRP

treatment diminishes the oxidative stress and the ovarian histopathology caused by

the bilateral adnexal torsion, while it increases the peritoneal vascular endothelial

growth factor5

•PRP treatment has improved vascularization and quality of an implant in an

autologous ovarian transplantation4

•PRP has promoted endometrial growth in women with poor endometrial quality6

PRP treatment in Gynaecology

1. Shawn M Briley et al.Reproduction 2016;0129 4. Bakacak et al. Gynecol Obstet Invest. 2016;81:225-31

2. Pietrzak and Eppley. J Craniofac Surg. 2005;16:1043-54 5. Callejo et al. J Ovarian Research. 2013;6:33

3. Borrione et al. Am J Phys Med Rehabil. 2010;89: 854–61 6. Chang et al. Int J Clin Exp Med. 2015;8:1286-90

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Our experience with autologous PRP treatment

• Endometrial treatment

• Women with a history of ET failures and thin endometrium

• Women with a history of chronic endometritis

• Ovarian treatment

• Menopausal women under the age of 54 years

• Peri-menopausal women under the age of 50 years seeking IVF with own eggs

Genesis Athens Hospital Ethics Committee approved the study protocol in accordance to the Helsinki

declaration and all participants gave informed consent

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Subjects Eight peri-menopausal women undergoing PRP treatment constituted the

study population. All subjects, aged 45.13±4.42 years, had absence of

menstrual cycle for 4.88±1.13 months.

The hormonal profile was determined before the PRP treatment and at

monthly intervals after the PRP treatment in order to monitor the ovarian

function. The presence of developing follicles was confirmed by ultrasound

scan.

Methods PRP was prepared using the RegenACR®-C Kit and was infused into the

ovaries using a transvaginal ultrasound-guided injection.

All patients underwent natural cycle IVF without any ovarian stimulation or

GnRH antagonist supplementation .

When a follicle of >16 mm was observed, ovulation triggering was achieved

with 5000 IU of hCG and follicle aspiration was performed 32 hours later by

the transvaginal route.

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Results:

The successful ovarian rejuvenation was confirmed by the

menstrual cycle restoration 1-3 months after the ovarian PRP

treatment.

The subsequent oocyte retrievals were successful in all cases,

resulting in 2.50±0.71 follicles of 15.20±2.05 mm diameter,

1.50±0.71 oocytes and 1.50±0.71 MII oocytes.

All mature oocytes were inseminated by ICSI and the 1.50±0.71

resultant embryos were cryopreserved at 2pn stage until transfer.

No embryo transfer has been performed.

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PRP treatment in menopausal women

• Scope:• To investigate whether PRP treatment could have revitalizing effects on the

dysfunctional ovaries of menopausal women.

• Study population:• Thirty four women in menopause (no menses >12 - 96 months), aged 45.26±6.12

years

• Primary outcome measure:• restoration of the menstrual cycle

• Secondary outcome measure:

- Improvement of hormonal levels (FSH,LH,E2,AMH)

- Folliculogenesis reactivation, oocyte retrievals with mature (MII)

oocytes and their reproductive outcome

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Results: • In 16 / 34 menopausal women (47%) menstrual cycle

restored within 1 to 3 months

• In 7 women follicles were observed on the first month immediately after treatment

• 6 women underwent oocyte retrieval

• In 3 cycles MII eggs were retrieved

• 1 patient proceeded to embryo transfer

• Singleton pregnancy -> spontaneous abortion 13th week of gestation

PRP treatment in menopausal women

Abstract accepted 7th International congress IVI 2017

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PRP Treatment in Menopausal women

No FSH AMH M/PAUSE(YRS)

AGE PRP Rx menses cyclesPOST-PRP

IVF (Natcycles)

Outcome

1 55,5->23 0,2 2 30 Dec 2015 16 5 2 MII VITRIFIED

2 65->43 0,01 1 46 May 2016 11 1 No egg

3 58->28 0,1 1 41 July 2016 9 1 No egg/ no menses now

4* 84->47 0,01 6 49 Sept 2016 2 0 No menses now

5 47->26 0,03 2 49 Sept 2016 2 0 No menses now

6 25->13 2,2 1 41 Sept 2016 8 2 1 MII vitrified

7 67->23 0,01 3 41 Sept 2016 2 0 No menses now

8 83->23 0,01 1 50 Sept 2016 2 0 No menses now

9 99->84 0,01 6 54 Nov 2016 2 0 Spotting every 2 months

10 118->29 0,03 1 48 Nov 2016 3 0 Menses

11* 110->59 0,01 3 49 Nov 2016 2 0 Menses

12 128->23 0,01 8 37 Dec 2016 4 1 No egg/ Still menses

13 149->… 0,02 4 39 Dec 2016 1 1 Clinical Pregnancy***

14 92->39 0,01 3 41 Dec 2016 4 0** Menses

15 88->67 0,5 2 47 Jan 2017 2 0 Menses

16 144->134 0,03 46 Jan 2017 1 0 Menses

*** Spontaneous miscarriage at 13th week of gestation ** Follicle observed but not OPU * Updated data on menstruation

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PRP treatment in menopausal women

Study conclusions:

Following PRP treatment there was successful menstrual restoration in almost half of women

Some women had retrieval of mature oocytes after natural cycle IVF and embryos after ICSI

Wider application:

PRP therapy may extend the fertility potential and help menopausal women to achieve a pregnancy with own oocytes

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PRP Treatment in peri-menopausal womenFSH < 15

COUPLES AGE IVF CYCLES EGG 2PN OUTCOME RESULT

1 41 1 1 1 ET Ongoing singleton pregnancy

2 47 1 2 2 ET Negative

3 46 4 5 5 ET Ongoing singleton pregnancy

4 39 1 1 1 Freeze

5 45 1 0 0

6 45 1 1 0

7 39 2 1 1 Freeze

8 43 3 0 0

9-24 33-50 NONE NATURAL COITUS OR CYCLE RESTORATION

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COUPLES AGE IVF CYCLES EGG 2PN OUTCOME RESULT

1 46 2 2 0

2 39 4 5 4 Freeze

3 45 2 2 0

4 49 4 1 0

5 50 2 1 1 ET Negative

6 47 2 1 0

7 29 2 0

8 46 6 3 3 Freeze

9 47 1 1 1 ET Negative

10 47 1 0

11 45 1 2 2 Freeze

12-27 32-49 NONE NATURAL COITUS OR CYCLE RESTORATION

PRP Treatment in peri-menopausal women

FSH :15 - 30

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COUPLES AGE IVF CYCLES EGG 2PN OUTCOME RESULT

1 48 1 1 0

2 46 1 0

3 47 1 0

4 44 1 1 0

5 42 1 1 0

6 44 1 1 0

7 45 2 0

8 48 2 1 0

9 38 3 3 1 Freeze

10 49 3 0

11 48 4 4 0

12 42 4 3 0

13 49 4 0

14 44 4 4 1 Freeze

15 45 6 3 2 ET Negative

16 48 8 5 3 ET Negative

17 35 1 1 0

18-19 36-49 None Presence of follicles Natural coitus

20-43 32-52 None NATURAL COITUS OR CYCLE RESTORATION

PRP Treatment in peri-menopausal womenFSH > 30

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Regarding the observed folliculogenesis

Many peri-menopausal women may maintain a restricted amount

of inactive primordial follicles, that could be activated by the PRP

growth factors for subsequent ovarian tissue regeneration and

maturate into preantral and antral follicles.

Indeed, platelet-derived growth factors (PDGFs), regulating cell

growth and division, have been shown to enhance blood vessel

formation and growth.

PDGFs have been localized in human oocytes and granulosa cells,

while their receptors in granulosa cells suggest a potential

association with primordial follicle activation.

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Regarding the observed folliculogenesis

The recent detection of ovarian stem cells1, germline stem cells1

and very small embryonic-like stem cells2 in human ovarian

surface epithelium as well as their ability to differentiate into

oocytes under certain conditions, create new data for the origin

of PRP-derived follicles.

Therefore, the continual flow of hormones and growth factors,

which may become temporarily available in the rejuvenated

ovary of peri-menopausal women and premature ovarian failure

(POF) patients by the PRP treatment, could give birth to 'new

primary ovarian follicles' and subsequently to antral follicles.

1. White et al. Nat Med 2012;18:413–421 2. Virant-Klun et al. Differentiation 2008;76:843–856

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Patient reasoning for ovarian PRP treatment

33%

17%

42%

8%

IVF

NATURAL COITUS

MENSTRUAL CYCLE RESTORATION

YOUTH

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INCREASE OF HEALTH LIMIT AND LIFE EXPECTANCYHELLENIC STATISTICAL AUTHORITY (ELSTAT) in collaboration with the European Common

Action and coordinated by the National Institute of health and Medical Research

o In the EU life expectancy at the age of 65 years old in 2011 was 18.0 years for

men and 21.4 years for women, an increase of more than one year compared

with the figures of 2005 (1.3 years for men and 1.2 years for women), touching

so highest average of 86.4 years for life expectancy of modern woman.

o On the basis of 2012 SILC evidence (Survey on income and living conditions of

Households), at the age of 65 years, women spend 7.3 years (35% of remaining

life) without limitation of day-to-day activities.

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TIME

In 2013 in the US, there were 677 births in women 50 years old and

older-over 600 deaths in 2012, according to CDC's National Vital

Statistics Report.

The largest increase was 14% in women aged 45-49, whose birth rate

jumped within one year: to 7.495 in 2013 from 7,157 in 2012."

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There are countries that have set an upper age limit in order to reduce

State spending on older women (State insurance agencies).

There are other countries where indirectly shift the responsibility to private

clinics that perform in-vitro fertilization and to the health care professional,

as is the case in the United Kingdom.

AGE LIMIT IN IVF AND THOUGHTFUL

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In countries with strict legislation and strong limitations on assisted

reproduction issues, as Australia’s age limit of 52 years , while Israel has set

the age limit for IVF at 54 years.

In European countries such as Croatia, Czech Republic, Estonia, Finland,

Ireland, Latvia, Luxembourg, Malta, Poland, Portugal, Slovakia, Slovenia and

Spain, there seems to be no similar restriction in age of the infertile women to

have access to assisted reproductive technologies (ART).

AGE LIMIT & ART IN EUROPE

Francesco Paolo Busardò, BioMed Research International, Vol. 2014, Article ID 307160, Review Article The Evolution of Legislation in the Field of Medically Assisted Reproduction and Embryo Stem Cell Research in European Union Members

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o In the USA there is great variety among the various States with

most of them not mentioning any limit (ASRM 2013).

o The advised limit by ASRM was increased to 55 years and all the

States of America tend to harmonize with it, and seems to affect

other scientific societies of infertility worldwide. (Austin J In Vitro Fertili.

2014;1(1): 3. Is There an Age Limit to Become Pregnant in the Ivf Era? Bruno Ramalho

de Carvalho, Center for Assistance in Human Reproduction, Brazil)

o Only minimal States have a limit of 45 or 50 years.

AGE LIMIT & ART IN THE U.S.

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HOW OLD IS TOO OLD: NO CLEAR - CUT ANSWERCASE:Omkari Panwar form India:70 yrs old delivered twins 2008

CONSIDERATIONS:

• Age of the mother

• Associated health complications

• Remaining life expectancy

• Proper screening medical and psychological of the mother to be

• Best interests of the child to come

• Social concerns

1. MacArthur et al. Menopause. 2016;23:799-802 2. Soderstrom-Antilla Hum Reprod Update. 2001;7:28-32

1,2

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Αγαπημένη λέξη και σεβαστή στην ελληνική κοινωνία, καταφύγιο για μικρούς και μεγάλους

The Family

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ΚΩΣΤΑΣ ΠΑΝΤΟΣ

ΤΑΣΟΣ ΚΩΝΣΤΑΝΤΟΠΟΥΛΟΣ

The Physicians

ΔΗΜΗΤΡΗΣ ΣΤΑΥΡΟΥ

ΜΙΧΑΛΗΣ ΓΡΑΜΜΑΤΗΣ

ΣΤΕΦΑΝΟΣ ΣΥΡΚΟΣ

ΝΙΚΟΣ ΜΠΑΘΡΕΛΛΟΣ

ΚΩΣΤΑΣ ΣΦΑΚΙΑΝΟΥΔΗΣ

ΒΑΣΙΛΗΣ ΚΕΛΛΑΡΗΣ

ΑΝΔΡΕΑΣ ΒΥΘΟΥΛΚΑΣ

ΓΙΩΡΓΟΣ ΚΟΥΜΑΝΤΑΚΗΣ

ΕΥΓΕΝΙΟΣ ΚΟΥΜΑΝΤΑΚΗΣ

ΓΕΩΡΓΙΟΣ ΜΑΡΟΥΛΗΣ

ΑΡΙΣΤΟΤΕΛΗΣΜΙΧΑΛΟΠΟΥΛΟΣ

ΓΕΩΡΓΙΟΣ ΖΟΥΜΗΣ

ΔΗΜΗΤΡΙΟΣ ΣΤΑΘΗΣ

ΝΙΚΟΛΑΟΣΝΙΤΣΟΣ

ΜΑΡΙΟΣΜΑΡΚΟΠΟΥΛΟΣ

ΜΑΝΟΣ ΠΡΟΜΠΟΝΑΣ

ΑΘΑΝΑΣΙΟΣΠΑΠΠΑΣ

ΑΛΕΞΑΝΔΡΟΣΔΕΡΠΑΠΑΣ

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GENESIS ATHENS CLINIC – THE EMBRYOLOGISTS

ΤΕΡΨΗ ΒΑΞΕΒΑΝΟΓΛΟΥ

ΜΑΡΓΑΡΙΤΑ ΧΡΟΝΟΠΟΥΛΟΥ

ΚΩΝΣΤΑΝΤΙΝΑ ΠΕΤΡΟΥΤΣΟΥ

ΡΕΝΑ ΑΓΓΕΛΗ

ΑΦΡΟΔΙΤΗ ΚΑΤΟΥΝΑ

ΜΑΡΙΑΦΑΚΙΡΙΔΟΥ

ΔΩΡΑΓΡΙΒΑ

ΕΦΗΚΥΡΙΤΣΟΠΟΥΛΟΥ

ΕΦΗΜΠΑΞΕΒΑΝΗ

ΧΡΙΣΤΙΝΑΜΑΡΚΟΜΙΧΑΛΗ

ΓΕΩΡΓΙΑ ΚΟΚΚΑΛΗ

ΑΛΕΞΙΟΣΦΑΛΔΑΜΗΣ

ΠΩΛΙΝΑ ΓΙΑΝΝΕΛΟΥ

ΧΡΥΣΟΥΛΑΚΑΡΑΛΕΥΘΕΡΗ

ΚΑΤΕΡΙΝΑΒΟΥΤΣΙΝΑ

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GENESIS Athens Clinic