HRANICE ŽIVOTA

ASISTOVANÁ REPRODUKCIA

Prof. RNDr. Michal Zeman, DrSc.

PriF UK, Bioetika

Hranice života

Počatie – Narodenie –

Dospievanie- Reprodukcia-

Postreprodukčný vek- Staroba-

Smrť

Fertilita– poznanie fyziológie reprodukcie

– poznanie antikoncepčných metód

– informované rozhodnutie o počatí

– plánované rodičovstvo

v škole a rodine mnohé tabu

BIOETIKA – zdôrazňuje právo človeka na

dostatočné kvalitné vzdelanie v súlade

s najnovšími poznatkami vedy

Nezávislosť sexuálneho styku od

reprodukcie u ľudí

- sexuálna receptívnosť počas celého cyklu

- sex - upevňovanie dlhodobých

párových vzťahov

- pro-kreačný sex sa stáva re-kreačným

Evolučné aspekty

- výhody a nevýhody „tabu“

- nedotknuteľnosť manželstva

nevera

- výrazný pokles reprodukčného fitness v

modernej industriálnej spoločnosti

Fyziológia reprodukcie

Semenníky a spermiogenéza

Nedeterminovaná mitotická aktivita spermiogónii

Hormonálna regulácia u samcov

▪ U ľudí - 250 000 oocytov, ale iba 400-500

ovuluje za život

estrogénov

▪ Folikuly – produkcia androgénov

gestagénov ➭

progesterón (neskôr corpus luteum)

▪ Folikulárny rast a diferenciácia je indukovaný

FSH a stimulačný IFG-I

Samičí reprodukčný systém

Oogenéza

Oogónie stratili mitotickú aktivitu

Menštruačný cyklus

hypofýza

ovárium

steroidy

uterus

Antikoncepčné metódy

• Koncepcia neplodných dní

• Fyzikálne metódy

• Hormonálne

Antikoncepcia – stará otázka

Čínska medicína – indukcie potratov

2 700 p.n.l.

Starý EgyptKahun papyrus – 1 850 p.n.l.

vaginálne pasty,

menzes indukujúce pasty

sexuálna abstinencia v určitých fázach cyklu

1500 p.n.l. - spermicídne účinky guličiek z

gumovníka s kyslým pH

Prirodzená kontrola reprodukcie- vajíčko schopné oplodnenia 24-36 h po ovulácii

- spermie môžu prežívať 48-56 hod. v reprod. trakte

ženy

- zlyhanie 2-24% v 1 roku

Rozvojový svet, nielen– prirodzené - lacné

– žiadne vedľajšie, negatívne dôsledky

Antikoncepcia – problém

Politický - Stanovisko štátu

Čína,

Arabské krajiny

NaboženskýKatolícke – encyklika Humanae Vitae

Islam

Hormonálna antikoncepcia

➢ výhody

➢ nevýhody

➢ akcepovateľnosť

➢ spoločnosťou (islam, kresťanstvo)

➢ samotnou ženou

Asistovaná reprodukcia15% infertilných párov

Pokles počtu spermií na polovicu u mužov za

posledných 50 rokov

113.106 ml – 1940

66.106 ml – 1990

Normospermia – WHO definícia (2010)Objem ejakulátu: 1,5 ml

Koncentrácia spermií: 15 miliónov/ml a viac

Celkový počet spermií v ejakuláte: 39 miliónov a viac

Celková pohyblivosť: 40 % a viac pohyblivých spermií

Progresivý pohyb: 32 % a viac

Morfológia: viac ako 4 % s normálnou stavbou

Vitalita: 58 % živých spermií

Leukocyty: menej ako 1 milión/ml

MEDICAL INFERTILITY

Affects 10-15% of couples attempting pregnancy

DISTRIBUTION OF CAUSE

FEMALE INFERTILITY

(from Ian Pike’s

guest lecture)

LIFESTYLE AND FERTILITY

OVERALL FITNESS AND THE CAPABILITY

TO BEAR HEALTHY CHILDREN DEPENDS ON:

1. OUR GENES

2. THE CONDITIONS UNDER WHICH WE LIVE

3. THE WAYS IN WHICH WE BEHAVE

INFERTILITY – THE INABILITY TO ACHIEVE PREGNANCY

1. MEDICALa) After 12 months of unprotected sexual intercourse or

b) Due to a diagnosed physical abnormality of the

reproductive system; e.g., blocked fallopian tubes

2. SOCIALNon-engagement in a heterosexual relationship

3. THE INABILITY TO CARRY A PREGNANCY TO LIVE BIRTH

MALE INFERTILITY

FERTILITY DECLINES WITH AGE

Female infertility increases from

30 years of age to the menopause

Genetic anomalies in men also increases with age

(from Ian Pike’s

guest lecture)

MANY CONCEPTUSES DO NOT SURVIVE

Human fecundity rate; i.e., the probability of achieving a clinical recognized

pregnancy within any given menstrual cycle, is about 25% and high levels of

fertilization failures or early developmental death, are the norm at conception

Spontaneous abortion is one of Nature’s ways to counter negative genetic and

environmental factors

MAXIMIZING FERTILITY AND REPRODUCTIVE OUTCOME:

GENERAL HEALTH ISSUES

THERE ARE SEVERAL THINGS POTENTIAL PARENTS CAN DO TO

SIGNIFICANTLY IMPROVE THEIR REPRODUCTIVE HEALTH AND REDUCE

THE CHANCE FOR ASSISTED REPRODUCTIVE TECHNOLOGY TREATMENT

i) NUTRITION AND REPRODUCTION

All essential nutrients in diet - women who are

significantly overweight or underweight can

have difficulty getting pregnant

ii) EXERCISE AND REPRODUCTION

Regular aerobic exercises but excessive can affect

ovulation and sperm count

iii) SUBSTANCE ABUSE AND REPRODUCTION

Alcohol, nicotine, illicit drugs and some medications

adversely affect the embryo, fetus and newborn

iv) FOLIC ACID AND NEURAL TUBE DEFECTS

Is recommended as daily food supplement

prior to conceptionBeans and green leafy vegetables are a rich source of

folic acid (from E. Hyams ‘Plants in the Service of Man’.

Dent & Sons, 1971)

MAXIMIZING FERTILITY AND REPRODUCTIVE OUTCOME:

GENERAL HEALTH ISSUES CONTINUED

v) TEMPERATURE EFFECTS AND SPERM QUALITY

Optimum spermatogenesis 4-7˚ C below body temperature

vi) PHYSICAL AND PSYCHOLOGICAL STRESS

A relationship between emotion and fertility exists

vii) REGULARITY OF INTERCOURSE

2-3 times per week, particularly around the time of ovulation

viii) SCREENING TESTS

Both partners have blood

tests taken for HIV

antibodies, hepatitis B&C,

and females for immunity to

Rubella (German Measles) –

the virus known to cause

major abnormalities in the

fetus if contracted during

early pregnancy

‘The Stairs of Age’ by Winter Carl

Hansson (1777-1805)

PART II : ASSISTED REPRODUCTIVE TECHNOLOGY (ART)

Since the first ‘test-tube’ baby Louise Brown was born in Britain in 1978,

several millions of children have been born through assisted reproduction

Social Impacts of Assisted Reproductive Technology

Donor insemination is more successful than partner insemination,

does not carry an increased risk of spontaneous abortion or

congenital anomalies, and has advantages over adoption in that the

child is genetically related to the mother and the couple can

experience conception, pregnancy and delivery

ARTIFICIAL INSEMINATION BY HUSBAND OR BY DONOR

INTRACYTOPLASMIC SPERM INJECTION (ICSI)

ICSI, in conjunction with IVF technology, has given

hope to men with sever infertility problems

Even immature spermatids (sperm precursor cells)

can be harvested and used to fertilize the egg

FEMALE-FACTOR INFERTILITY: IN VITRO FERTILIZATION (IVF) TECHNOLOGY

AIM OF TREATMENT

1. Menstrual Cycle Management

2. Control Ovaries by Drugs

a) Drug 1 – block usual control mechanism

from brain X ovary

b) Drug 2 – Direct stimulation to the ovary

c) Develop a batch of eggs

IN VITRO FERTILIZATION (IVF) TECHNOLOGY CONTINUED

3. Prepare Eggs for Fertilization

4. Drug 3 – induce ovulation

5. Harvest eggs

6. In vitro fertilization

PROTOCOL - IVF TREATMENT CYCLE

Key

U/S Ultrasound Scan

* FSH daily injections

Blood hormone test

(E = estradiol 17β)

a GnRH analogue – daily

injection(from N.S. Fertility)

TECHNOLOGIES IN COMBINATION WITH IVF TECHNOLOGY

PREIMPLANTATION GENETIC DIAGNOSIS (PGD)

Alternative to ultrasound, amniocentesis or chorionic villus sampling

STORAGE FOR FROZEN EMBRYO TRANSFER

SPERM, EGG AND EMBRYO DONATION

1. Female Infertility

Premature Menopause

Genetic Disease Carrier Donor Egg

Age Factor & Chronic IVF Failure

Lack of / Unsuitable Uterus Surrogacy

2. Male Infertility

Abnormal Semen Donor Sperm

3. Couple Infertility

Chronic IVF Failure Donor Embryo

Bioetické limitácieVeľká Británia – zákon o asistovanej reprodukcii

Žene sa nemá poskytovať reprodukčná

asistencia, kým sa nezabezpečí welfare

dieťaťa, ktoré sa má narodiť v dôsledku

ošetrenia (vrátane otca dieťaťa)

a akéhokoľvek iného dieťaťa, ktoré môže

byť poškodené zákrokom

Identifikácia donorov gamiet – ÁNO/NIE?

Švédsko 1985 –

Dnes

donori musia byť registrovaní

Povedať- Nepovedať dieťaťu o jeho

počatí

Dnes - väčšina manželov

– ANO o pôvode dieťaťa

SEX SELECTION AND DESIGNER CHILDREN

ASSISTED REPRODUCTION : RISKS AND UNCERTAINTIES

Some researchers are questioning the safety of technologies such as ICSI

and other invasive techniques, claiming that they may be linked to increased

rates of birth defects and rare genetic imprinting disorders

Dolly the sheep – the world’s first cloned mammal was euthanized 14th February, 2003

(The Japan Times, February 16, 2003)

TECHNOLOGIES IN COMBINATION WITH IVF TECHNOLOGY CONTINUED

ĎAKUJEM

Research into cell and tissue

differentiation using cultured

embryonic stem cells from

humans, and other species,

may enable the control of

differentiation and

dedifferentiation in somatic

cells. This could allow the

production of tissues with

enhanced stem cell

components that may be

used as universal donor cells

for transplantation

(To-day’s Life Sciences, March/April 1999)

BALANCING RISKS AND

UNCERTAINTIES