IT ALL STARTS WITH AN EGG AND A SPERM
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IT ALL STARTS WITH
AN EGG AND A SPERM:
NATURAL FERTILIZATION
How does human fertilization occur? At first sight, a simple question – you’ve known the answer for years.
Or you thought you did, because it’s not really as straightforward as that. A complicated biochemical and
anatomical background underlies the process of merging a female egg and a male sperm to form what
becomes a baby. An understanding of this background is especially vital for couples unable to conceive
but who can be helped medically.
THE FEMALE REPRODUCTIVE SYSTEM
egg
A normal human female is born with about 300,000 to 400,000 ovary
eggs (also known as egg cells or ova) stored in two ovaries. She will fingerlike
produce no further eggs during her lifetime. On the contrary, a large projections
number of these eggs die through a process of natural wastage,
leaving about 100,000 to 200,000 by the time of puberty. The fallopian tube
number remaining decreases over time until none are left, usually
womb
at the age of about fifty, which marks the onset of menopause.
The ovaries normally release one ripe egg every four weeks during
a woman’s fertile years. This is known as ovulation. Finger-like vagina
1
projections at the top of one fallopian tube catch the egg. The
1| A woman’s reproductive organs.
egg is ready for fertilization by a sperm (from the male) while it is
inside the fallopian tube.
Cilia (tiny hair-like projections) covering the inner wall of the
fallopian tube gently waft the egg down to the uterus (or womb).
Meanwhile, the lining of the uterus (the endometrium) has
thickened in preparation for the arrival of an embryo.
Frequently asked question
If the egg is not fertilized or the embryo fails to implant in the Does ovarian stimulation affect the store
uterus, the mucous lining rapidly breaks up and is shed via the of eggs resulting in early menopause?
vagina. This process is known as menstruation (having a period). Find the answer on p. 80.
THEORY
13
THE MALE REPRODUCTIVE SYSTEM
Sperm (spermatozoa or sperm cells) are produced in tiny tubes
(tubules) inside the male’s testicles (testes). Sperm production
brains begins in puberty and continues for the rest of a man’s life.
Lesser known is the fact that sperm production and maturation is
controlled by the same hormones that regulate women’s menstrual
GnRH cycles: the gonadotrophins LH and FSH (see illustration 5 for the
abbreviations). Together they stimulate the male reproductive
hypofyse
organs (gonads) into the production and the ripening of sperm
FSH LH hypothalamus cells.
Gonadotrophins are secreted by the hypofyse, a small gland
in the brain which is controlled by the hypothalamus. The
hypothalamus secretes at regular intervals a hormone called GnRH
or Gonadotrophin Releasing Hormone, in a set rhythm dictating
the release of FSH and LH. During the process of production and
penis
ripening of sperm the reproductive organs subsequently start to
testosterone produce sex hormones. In the male, this is primarily testosterone.
testicle Testosterone
2 This is the hormone which turns a boy into a man. Production of
this hormone begins at puberty, from
bladder seminal
vesicle which point on it controls the sexual
function and libido of the man. Is is also
vas deferens
responsible for the maturation of sperm
prostate
gland urethra cells. Production of testosterone peaks
epididymis
around the age of 30-35, then gradually
penis
begins to decline.
testicle In the male ‘cycle’, testosterone levels are
3 4 monitored in the brain. If sufficient levels
are present, the secretion of GnRH slows down, resulting in a lower
2| The hormonal ‘cycle’ of a man.
level of gonadotrophins produced. Similarly, if testosterone levels
3| A man’s reproductive organs.
are low, e.g. because the testis are producing less, the brain gets
4| Testosterone Builder. the message that more FSH and LH are needed. In response the
Men who take testosterone in order to increase
their muscle mass are giving an incorrect signal
secretion of GnRH accelerates, causing more gonadotrophins to
to their brain, i.e. that sufficient male hormone be released.
is present in the body. This leads to a halt in
gonadotrophin production. But gonadotrophins are
necessary for the production and maturation of The sperm cells’ itinerary
sperm cells. Or how taking testosterone can lead
to a significant reduction in sperm production and As said before sperm cells are produced in tubules inside the
hence to infertility. testicles. The production itself is a complicated process of cell
division and cell differentiation which takes about three months
in total. But of course the process occurs in thousands of tubules
and at different stages constantly, so that there is always a supply
of mature sperm available.
After its production in the testicle, the sperm travels to the
epididymis, which consists of one long, tightly coiled tube. The
THEORY
14sperm remains here for about a week, during which it continues to Normal sperm according to WHO-norms
mature and become more motile. Semen
The epididymis also serves as a reservoir. During an orgasm, sperm volume 2,0 ml or more
cells are expelled from the epididymis and set out on their journey pH 7,2 – 7,8
Sperm
to the outside world via the vas deferens. On their way out they are
concentration 20 million/ml or more
mixed with a nutrient-rich plasma from the prostate and seminal
total count 40 million or more
vesicles. They are then ejaculated trough the urethra in the penis. progressive motility (fast or
A normally fertile man will ejaculate between 1.5 and 4 ml of slow forward movement) > 50%
semen containing some 20 to 200 million sperm per ml. See the or
World Health Organisation (WHO) overview for other standards fast progressive motility > 25%
which ‘normal’ sperm must meet. normal formation > 30%
vitality > 50% live
white blood cells < 1 million/ml
Semen reaching the vagina undergoes a drastic transformation
within less than half an hour, changing from thick and sticky to
thin and fluid. Large numbers of sperm simply flow out of the
vagina, while most of the rest cannot get past the mucous around
the cervix (neck of the womb). A few hundred sperm at most – brain
motile and well-formed sperm – succeed in entering the uterus
and climbing to reach one of the fallopian tubes. If a ripe egg is
GnRH
waiting there, there is a chance it will be fertilized – in principle
by a single sperm.
pituitary gland
FSH LH hypothalamus
THE MENSTRUAL CYCLE
ovary
A normal menstrual cycle lasts four weeks, although this time may
vary greatly from one woman to another and one cycle to another. oestrogen progesterone
A menstrual cycle begins with the ripening of an egg and ends in a
period (menstruation) or pregnancy.
womb
From day one to ovulation mucos
lining
(follicular phase)
The menstrual cycle is triggered by a low level of oestrogens 5
(female hormones) in the blood. This causes the hypothalamus, a GnRH (Gonadotrophins Releasing Hormone):
encourages the menstrual cycle.
neural control centre at the base of the brain, to secrete GnRH (see FSH (Follicle Stimulating Hormone):
illustration 5). GnRH stimulates the pituitary gland, the master develops the follicles in the ovaries.
LH (Luteinising Hormone): encourages ovulation.
endocrine gland located below the hypothalamus, to produce hCG (Humane Chorion Gonadotrophin) or
follicle stimulating hormone (FSH) and luteinising hormone (LH). pregnancy hormone: supports the further
development of the embryo into a baby.
These two hormones directly stimulate the woman’s reproductive
organs (gonads) and are therefore called gonadotrophins. GnRH 5| Hormones involved in the menstrual cycle and/or
the IVF-treatment.
causes them to be ‘released’: hence the name Gonadotrophins
Releasing Hormone.
FSH stimulates the development of several ovarian follicles, small
sacs in the ovaries filled with liquid and each containing an egg.
Oestrogens secreted by these follicles cause the endometrium to
thicken in preparation for the possible implantation of an embryo.
Oestrogen secretion by the follicles causes oestrogen levels to rise,
THEORY
15sending a message to the brain to slow down the release of GnRH.
MENSTRUAL CYCLE
As a result FSH production is reduced too, which stops further
Maturation of the egg within the follicle follicle development and causes all but one to die. Nevertheless
there is always one dominant follicle that survives by adapting to
Ovulation the low FSH levels, and this follicle alone continues to grow.
LH surge Under the influence of FSH and LH the egg in the dominant follicle
Luteinising ripens. When oestrogen levels are sufficiently high an LH surge
hormone
occurs (a sudden increase in the amount of LH released), causing
Progesterone final maturation of the egg. The egg is now mature and ovulation
FSH can take place. There are approximately 12 to 40 hours between
the LH surge and ovulation. The LH surge occurs around day 12 of
a 28-day cycle, with ovulation occuring at around day 14.
Oestrogens
MEN STRUAL C YCLE
Endometrium
Days 4 8 12 16 20 24 28 DAY
Ovulation
6
1 14 28
fallopian tube
FOLLICU L AR PHASE LUTEAL PHA S E
Maturation of the egg Possible fertilization
in the follicle followed by
possible implantation
OVU L ATION PR EG NANT
egg OR
follicle M E N STRUATION
7
From ovulation to day 28
(luteal phase)
After ovulation, the ripe egg travels through the fallopian tube to
the womb. The remaining empty follicle in the ovary turns into
a yellow glandular mass of tissue (corpus luteum). This does not
ovulation
only secrete oestrogens (as the follicle did) but also progesterone.
Together these hormones stimulate the endometrium to thicken as
well as suppressing the production of FSH and LH by the pituitary
gland.
Pregnancy
An egg may be fertilized up to about one day after ovulation.
yellow mass of tissue
A sperm retains its ability to fertilize an egg up to around two
8
days after ejaculation. Thus, a woman has three days of effective
6| Hormonal changes during the fertility per cycle.
menstrual cycle.
Fertilization takes place when the spermatozoa, having reached
7| Graphice representation of the the distal portion of one tube, succesfully penetrates into the egg,
menstrual cycle. In practice, ovulation is
not that easy to predict. this creating an embryo. The fresh embryo is then undergoing
successive divisions and is transported during a six day period
8| From follicle to yellow mass of tissue.
towards the uterine cavity. By then it has become a blastocyst
(multi-cellular germinal vesicle). It implants in the uterine mucosa
THEORY
16and starts to secrete hCG. This hormone can be identified in female
blood (or urine), which makes diagnosis of pregnancy possible.
During the first trimester hCG acts on the corpus luteum, which
then continues to produce oestrogens and progresterone. During
early pregnancy (first trimester) this hormonal cooperation sustains
embryo development.
This function is subsequently taken over by the placenta, an
organ which sees to the nutritive exchanges between mother and
foetus. By that time, the evolution of the pregnancy has become
autonomous.
Menstruation
If pregnancy does not occur, the corpus luteum will begin to break
down about ten days after ovulation. This causes the oestrogen and
progesterone levels to fall sharply, leading to the shedding of the
endometrium at around day 28 of the menstrual cycle. The woman
then menstruates, and the secretion of GnRH by the hypothalamus
and of FSH and LH by the pituitary gland begins all over again.
The first day of menstruation is also the first day of the new menstrual cycle. This
is why the timing of the IVF treatment is always counted from of the first day of
(red) bleeding (= day 1).
THEORY
17GIVING NATURE A HELPING HAND:
IN VITRO FERTILIZATION
If pregnancy through the usual method is not possible for you,
artificial insemination (see further, p. 53) or in vitro fertilization
(IVF) may be the solution.
REDUCED FERTILITY
Our knowledge of the human reproductive system and the
hormones which control it, teach us also what can go wrong:
weg van
• defective hormone production in the brain;
de zaadcellen
• defective hormone production in the reproductive organs;
9 • insufficient production of sperm cells;
• poor quality of sperm;
• problems related to the ripening process of egg cells;
• insufficient supply absence of eggs, poor quality of eggs;
• obstructions in the path of the sperm within the male
reproductive system;
• patency of the fallopian tubes;
• incorrect timing or location of the unity between sperm and
egg;
• implantation problems of the embryo.
10
We distinguish different causes of infertility:
9| The itinerary of the sperm cells through the male … • gynaecological causes: i.e. the woman’s fallopian tubes are
10| … and thereafter through the female genital blocked or her uterus has certain malformations;
organs. • hormonal indications: i.e. ovulation does not occur or is
disturbed;
• andrological indications: the man doesn’t produce (enough)
healthy sperm cells; and
• immunological indications: man or woman produce sperm-
neutralising antibodies
Furthermore certain couples still aren’t expecting a child after
having regular sexual intercourse without any form of birth
control for a year or two, with the doctors failing to identify any
discernable cause. These cases are called idiopathic or unexplained
infertility.
THEORY
1811 12
THE TREATMENT IN A NUTSHELL
An IVF treatment is designed to help couples who suffer from
one or more of the aforementioned fertility problems. The natural
menstrual cycle will then be temporarily replaced by a medically
induced cycle.
Treatment begins with hormonal stimulation of the woman’s
ovaries. The aim is to produce several eggs in the course of one
menstrual cycle.
The ripe eggs are harvested (egg pick-up) from the ovaries just
13
before ovulation, using a very fine hollow needle. They are then
mixed in the laboratory with selected sperm provided by the man.
This may even be one single sperm cell, which is injected directly in
the egg. In this case we talk about ICSI.
If all goes well, some of the eggs will be fertilized and begin to
develop into embryos. One or two embryos are then transferred
to the woman’s uterus (embryo transfer), where we hope one will
implant itself and grow into a healthy baby.
In the past, two or three embryos used to be transferred, to increase
the chances of a successful implantation. However, the chances of
a multiple pregnancy (twins, triplets) are also increased. Improved 14
medical techniques often allow the transfer of only one embryo
11| Egg cumulus: the egg is in the top right-hand
nowadays, thus eliminating the chances of a multiple pregnancy, corner surrounded by feeding cells.
and at the same time reducing the general health risks for woman
12| Sperm under a microscope.
and child.
13| Eggs and semen are mixed in a glass dish
Any remaining good quality embryos are frozen and stored for (classic IVF).
later use if the first attempt does not result in pregnancy or if the
14| Insemination via ICSI: the sperm is sucked into a
woman wishes to have more children later. This avoids unnecessary needle and injected into the egg.
further stimulation of the ovaries and subsequent procedures.
Chances of a successful transfer are proportional to the number
of thawed embryos because they don’t all survive the thawing
process. Even if they are all of a good quality, the survival rate is
fifty percent on average. So it is perfectly possible that a couple
has embryos from a previous treatment, but still has to repeat the
entire IVF treatment for another attempt or for a second child.
THEORY
19Not easy but not painful either
In vitro fertilization is both a minor and a major treatment.
Physically, the demands are relatively small in that IVF involves a
series of minor, low-risk procedures, usually with little or no pain.
The drugs used may cause some short-term discomfort, but these
side-effects are not serious or lasting. Moreover IVF treatment is an
out-patient procedure and does not require you to stay overnight
in UZ Brussel.
However, IVF does make great mental demands on a couple. The
treatment involves many procedures and special routines and will
require a few (temporary) changes to your normal lifestyle. Of
course, you are certain to feel some stress, uncertainty and worry;
this is all quite natural and is focused on one crucial question:
will the treatment be successful? The effects of this will place a
heavy psychological burden on you, and you may find it extremely
wearing.
The CRG at UZ Brussel tries to give each couple every help and
guidance they may need. Helping you to satisfy your natural desire
for a child and ensuring your comfort during the treatment are
both very high on our list of priorities.
PREGNANCY IS NEVER A CERTAINTY
The most important conclusion from practical experience is
that your individual chances of success are very difficult to
predict beforehand. Apart from the age of the woman the type
15 of treatment, the cause of the fertility problem, and chance play
a role. Sometimes the exact same treatment will produce results
after the second or third attempt. Why not the first time is not
always determinable. That is why counsellors nor doctors will
respond to questions about the chances of success of an individual
treatment. The risk to create unrealistic expectations – or on the
contrary erroneously stifle justified hope – is too great.
Based on our extensive experience for many years standing and
after examination of both partners we can of course give you a
general idea as to what the odds are. We’ll always try to assess your
medical chances as accurately as possible. On the whole we can
affirm that IVF/ICSI certainly is worth a try for many couples, but
16 that it doesn’t necessarily always results in the birth of a child.
15| Fertilized egg, the day after IVF, still surrounded
by sperm.
16| If everything goes well, the end result is
pregnancy.
THEORY
20Statistic chance of delivery
100 1 2 3 4 5 6 7 8 The average chance of success of
an IVF treatment is closely related
90 to the woman’s age, as can clearly
be seen in this graph.
80
70
60
50
Number of expected deliveries (out of 100 women)
20–29 age
40
30–34 age
30 35–37 age
average > 20–37 age
20 38–39 age
40–43 age
10 > 43 age
0
Number of fertilization cycles (IVF or ICSI)
This graph shows the relation between the expected percentage
of deliveries (not pregancies!), the woman’s age and the number
of IVF or ICSI attempts. The vertical axis shows how many women
(out of a hundred) of what age may give birth to a baby after an
IVF or ICSI treatment; the horizontal axis shows after how many
attempts.
Example: of the 100 women in the 20 to 29 age group who started
with IVF – ICSI, 37 may be expected to have given birth to a baby
after the first attempt, 60 after the second attempt and 73 after
the third attempt.
In terms of ‘average’ success – i.e. all ages and irrespective of the
number of attempts – the following figures are available. Of 3,600
pick-ups performed in the course of one year by the CRG at UZ
Brussel, nearly 90% produce eggs which are fertilized to become
viable embryos ready for transfer to the uterus. These embryo
transfers produce a pregnancy in 30 percent of cases on average.
So almost 25% of the original pick-ups result in the live birth of
a baby.
THEORY
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