Brochure Infertility Unit

Infertility unit
Infertility unit
Content
General information concerning infertility
How to contact the infertility unit of the
University Women’s Hospital of Basel, Switzerland
The natural menstrual cycle
Hints for good reproductive health
Unwanted childlessness
and the psychological burden of infertility
Gynaecological infertility diagnostics
Examination of the uterus and the fallopian tubes
Preparation of the long desired pregnancy
Causes of infertility in the male –
examination of the male patient
Treating the causes of infertility themselves
Methods of assisted fertilization
Swiss law on reproductive medicine
Stimulation of the ovarian function
for assisted fertilization
There are, however, various clearcut disadvantages
related to the ovarian stimulation
Treatment with the “long protocol”
Treatment with the “short protocol”
Details about the stimulation of the ovaries
Triggering injection for ovulation induction
Aspiration of the follicular content for oocyte retrieval
Semen collection and the preparation
of the spermatozoa for assisted fertilization
Aiding the implantation of the embryo
through “assisted hatching”
Replacement of the fertilized egg into the
uterine cavity
Yellow body or luteal phase of the cycle
Cryopreservation of supernumerary oocytes
in the pronucleate stage
Unsuccessful treatment
Pregnancy
Conclusion
Counseling and psychological advice
Treatments of international patients
Acknowledgements
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Preface
Dear couple
Learning to deal with the diagnosis of infertility can be quite
daunting for anybody. The reasons for infertility involve complex biological as well as psychosocial processes. Being well
informed about the basic biological factors as well as diagnostic and treatment options can help you to deal with the
psychological and physical stresses related to the infertility.
With this booklet, we will try to explain the biology and
physiology of human reproduction from fertilization of the
egg through pregnancy. We hope that you will be able to use
this as a guide during your treatment. It is specially tailored
to the modes of treatment offered in the Division of gynaecological endocrinology and reproductive medicine at the
University Women’s Hospital of Basel, Switzerland.
Please read the information provided thoroughly. We will
be available to answer any of your questions and encourage
you to inform your own gynaecologist, family doctor or urologist. It is sometimes useful to gain information from other
sources too in order to provide you with a complete overview of the issues.
Prof. Dr. med. h. c. mult. W. Holzgreve
Department chief, University Women’s Hospital
Prof. Dr. med. Christian De Geyter
Division chief, gynaecological endocrinology and
reproductive medicine
Dr. rer. nat. Maria De Geyter
Head of the laboratory
Dr. med. S. Steimann
Senior physician
5
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General information concerning infertility
Infertility is defined as the inability to conceive a child after
one year of regular unprotected intercourse according to
the definition of the World Health Organization. In Western
Europe approximately 12 to15 % of all couples are affected
by infertility. In Africa this rate may be much higher, affecting as many as 30 % of all women during their reproductive
life span.
Even in the event that a pregnancy does not occur during
12 months of unprotected intercourse, there is still a chance
of you becoming pregnant spontaneously. Statistics show
that in approximately 1% to 3 % of menstrual cycles a pregnancy can occur, however, the probability of you becoming
pregnant does become smaller as time goes on.
You have now decided to undergo counseling for infertility. We would like to inform you at this time that there are
other avenues open to you concerning having a child. Adoption or foster child care can be a satisfactory alternative in
this situation.
Psychological counseling concerning infertility and coping strategies can be of tremendous help in dealing with
these issues.
If you should decide to undergo treatment for infertility, it
is important to know that the diagnostic testing as well as the
treatment takes some time. The course of treatment consists
of a series of systematically and logically constructed steps
to help you overcome the problems of infertility. This process, which is organized according to well-known principles
of medicine within this field, consists of several phases.
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1. Diagnostics
The aim of the diagnostic phase is to uncover any medical
conditions which can lead to infertility in both the man and
the woman.
2. Overcoming the problems causing infertility
In the initial phase, all medical conditions will be treated.
This also includes treatment of conditions which can hinder
carrying a pregnancy to term. For example, hypothyroidism
can cause infertility yet can be easily corrected with substitution therapy. However, it is usually not necessary that all
conditions be treated. In many cases, correcting just a few of
these may already lead to a successful pregnancy.
3. Overcoming infertility without correcting pathological
conditions
If after conducting extensive diagnostic tests there is no clear
reason or condition that can be found to explain the infertility, or those conditions present cannot be treated, then the
next step is to attempt to make use of the residual potential
of the patients. This is accomplished through the use of different procedures of assisted fertilization.
In the infertility unit of the University Hospital of Basel we
offer a full range of treatment options for assisted fertilization
to help you attain your goal.
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How to contact the infertility unit of the University
Women’s Hospital of Basel, Switzerland
In order to make an appointment in the infertility department
for the initial counseling and further treatment, you can reach
us at the following number: ++41 61 265 93 37 (for international patients see page 62).
Before coming to your appointment you will have to
register at the reception desk of the unit, which is located
in the policlinic of the University Women’s Hospital. After
initial registration your dossier will remain in the office of the
infertility unit.
The infertility unit consists of three examination rooms as
well as three conference rooms. Five specially trained nurses
and three physicians will be responsible for your care.
In addition, we have special office hours designated for
the diagnosis and treatment of male infertility. For registration of the appointments please call the number mentioned
above.
The initial appointment takes approximately one hour.
It is necessary to gain as complete a picture as possible
of the medical state of the patients. Through a detailed case
and family history we attempt to gain information about
past and present conditions as well as those known in the
family of the patient which could affect fertility. It is an advantage for both the man and woman to be present during
this interview.
In order to simplify and speed up the process, it is recommended that you bring copies or originals of all previous examinations (blood tests, X-rays, operation protocols,
discharge summaries, etc.). If possible, a summary of diagnostics and treatments from your gynaecologist is always
useful because it helps to avoid unnecessary tests and limits the costs.
As team of the infertility unit we consider ourselves
as partners of your local gynaecologist. For the duration
of your treatment we will be responsible for your care because we have special training as well as special equipment
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for the treatment of infertility. We will remain in close contact with your gynaecologist through telephone calls as well
as letters throughout the treatment. We encourage you to
seek a second opinion at any time during your treatment
here.
Reception of the Division of
Gynaecological Endocrinology and
Reproductive Medicine at the
University Women´s Hospital of Basel
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The natural menstrual cycle
The menstrual cycle has a duration of 28 days, although
shorter and longer cycles do occur. The first day of the period
is considered to be day 1 and the cycle ends on the last day
before the next period begins. During the first seven days,
the maturation of several follicles occurs in one of the ovaries. This takes places through a delicate interplay between
the pituitary gland and the ovaries which allows one egg to
be selected for ovulation. The fertility of a woman is highly dependant on the number of follicles which are available
for ovulation. In other words, the more follicles a woman
produces, the higher the chance of getting pregnant. Transvaginal ultrasound examinations allow an exact determination of the number and characteristics of the ovarian follicles
and allow the physician to assess the receptivity of the ovaries to future hormone treatment. After the initial development of several follicles, only one will be selected for ovulation during the final stages of follicular growth.
Every ovarian follicle contains an egg (e.g. oocyte), at
least at the beginning of its development. Through stimulation by the pituitary gland only one follicle (the dominant
or Graafian follicle) will be activated, so that a maturation
process occurs which then leads to ovulation. The mature
egg then proceeds through the fallopian tube. Ovulation
does not occur if the follicle has not, for some reason, received an adequate hormonal supply. This may be the case
in older women approaching menopause or in very young
girls. In the latter this is due to the immaturity of the pituitary gland.
After ovulation has occurred, the follicle (a fluid filled
sack which contains an egg) becomes a corpus luteum
(yellow body of the ovary) which is responsible for preparing the uterus (womb) for the maintenance of pregnancy.
The corpus luteum usually remains active for up to 12 days.
If the lifespan of the corpus luteum is shortened for any
reason (less than 10 days) or does not function properly so
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that implantation cannot take place, then the woman is suffering from luteal insufficiency or weakness of the yellow
body of the ovary.
Hormones are substances produced in the body which
have specific effects on organs in the body. The following
hormones play an important role before and during pregnancy.
Estradiol (estrogen) is the name given to a family of ovarian hormones which are predominantly produced by the follicle and then released into the bloodstream. The amount of
hormones produced is directly proportional to the number of
follicles present. When several follicles are stimulated (for example hormones given during fertility treatment) then there
will be a higher level of estrogen in the bloodstream.
Progesteron is the hormone produced by the yellow body of
the ovary (Corpus luteum). It is primarily produced in the second half of the menstrual cycle and stimulates the secretion
of nutritional substances through the lining of the uterus.
FSH follicle stimulating hormone, produced in the pituitary
gland, regulates the growth of the ovarian follicle. Under its
influence the follicle produces estrogen as well as controls
the growth and function of cells found within the follicle.
These cells provide the egg with nutrients through extensive
intercellular connections with the maturing oocyte.
LH luteinizing hormone, also produced in the pituitary
gland, stimulates the production of small amounts of male
hormones in the ovaries and stimulates the ovulation of the
dominant follicle. In the second half of the cycle it stimulates the production of the progesteron through the corpus luteum.
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Prolactin is the hormone that stimulates the production of
milk in breastfeeding women. It is also produced in the pituitary gland together with FSH und LH. Excessive prolactin
levels can lead to irregular menstruation, deficiency of the
ovaries, and testicles. It is important to rule out a tumor in
the pituitary gland which can lead to elevated levels of prolactin. It is usually a benign tumor. Prolactin is also secreted
in excessively stressful situations.
HCG human chorionic gonadotropin is the “pregnancy”
hormone. It is produced by a part of the placenta, not the
embryo itself, and stimulates the release of the yellow body
hormone through the yellow body. A continuous and dynamic rise of HCG during early pregnancy is necessary for the
maintenance of a healthy pregnancy.
Hints for good reproductive health
The causes of infertility are manifold. Some of them occur
during childhood or adolescence and are difficult or impossible to treat. On the other hand, however, there are also
conditions which result from the advanced age of the patients
and are the consequence of a natural decline in the fertility.
A good quality of life and general healthy living habits
contribute substantially to helping you achieve your goal of
conceiving. We would like to share a few tips with you at
this time which have been proven to improve chances of
pregnancy.
Sedentary lifestyle and obesity
While it is well-known that an intensive training for sports can
lead to fertility problems in women, there has been no conclusive evidence concerning the negative effects of sitting
for long periods of time on male fertility. However, the testicles are the only organs in the body which require a lower
temperature than normal for optimal function. All situations
which lead to a constant elevation of the temperature of the
testicles can cause impaired sperm production. The following situations should be avoided.
• Wearing tight underwear which press the testicles close
to the body.
• Sitting for long periods of time without changing position
• Constant and excessive contact with heat
A sedentary lifestyle (lack of exercise) leads to obesity. Being overweight can lead to irregular menstruation, and extreme adiposity is coupled with a higher complication rate
during pregnancy. It is a known fact that overweight men
often have fertility problems due to the production of estrogen in adipose tissue which leads to compromised sperm
production.
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Strong smoking
Excessive smoking leads to premature loss of follicles. Women who smoke reach menopause earlier than women who
do not. It has been proven in studies that fertility therapies
are not as effective in smokers and the rate of spontaneous
abortion is higher.
In addition, it is known that smoking reduces the capability of the placenta to nourish the fetus and the birth weights
of children born to smokers are reduced.
Men who smoke also suffer from compromised fertility.
The harmful substances in cigarettes become concentrated in the egg and therefore are present in higher levels in
the embryo. It has been successfully documented that the
children of male smokers suffer from cancer at a higher rate
than those of non-smokers.
Alcohol
Consumption of alcohol raises levels of estrogen in both men
and women, which leads to impaired semen and follicle production respectively. During pregnancy itself, drinking large
quantities of alcohol can lead to a set of symptoms known
as “fetal alcohol syndrome”. This includes mental retardation
and deformation of the fetus.
Cannabis
Cannabis is considered to be a “soft” drug and judged therefore not to be dangerous. Studies, however, have shown cannabis to have serious side effects. The smoke of marijuana
contains 50 to 100 more carcinogenic substances than a cigarette of the same weight and stay in the body much longer than those from cigarettes. In addition to these side effects, cannabis can negatively affect the production of pituitary gland hormones so that the menstrual cycle and ovulation are disturbed. Impotence can also occur with cannabis use. Long-term consumption of the drug compromises
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semen production and causes shrinkage of the testicles. In
summary, it can be stated that cannabis has both long- and
short-term negative effects on male fertility.
During pregnancy the by-products of cannabis consumption are able to cross the barrier of the placenta and reach
the fetus. This causes growth retardation and can cause
behavioral abnormalities similiar to fetal alcohol syndrome
after birth.
Unwanted childlessness and the
psychological burden of infertility
Inability to have a child has been defined as a disease according the World’s Health Organization (WHO), because it can
have a negative effect on the mental as well as the physical
health of the patients. The burden is especially traumatic for
the woman as she will be reminded with every menstruation
that she is once again not pregnant.
Through progress in modern reproductive medicine
many but not all couples can be helped. Many patients find
solace after being able to educate themselves about various forms of infertility. It sometimes happens that couples
who have been informed about their particular condition no
longer wish to proceed with infertility treatment. Sometimes
these women later become pregnant spontaneously. If this
should occur, we would be happy to hear from you. Through
this information we will be able to evaluate our techniques
and become more able to help others in the future.
Many couples decide to make use of assisted reproductive techniques. Going through some of these procedures
can pose a tremendous psychological as well as physical
burden on the patients, especially where the monitoring is
intense, as with in vitro fertilization. These techniques can,
on the other hand, greatly increase the chance of getting
pregnant. Undertaking this form of therapy can, however,
put considerable emotional pressure on the patient as she
is confronted with her inability to conceive with each step,
which can lead to depression. The ups and downs which a
woman experiences from each good and poor report from
the gynaecologist can be especially taxing. Women who previously suffered from depression are particularly vulnerable.
Going through fertility treatment can, in the case of a negative outcome, cause a re-appearance of previous psychiatric conditions.
In order to deal with the stress of the fertility treatments,
it is extremely important for the patient and her partner to be
well-informed. We encourage you to carefully read through
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this information booklet in order to gain an overview of the
causes of infertility as well as therapies available. Psychologists have conducted studies on patients concerning coping strategies and success rates of ART. They were able to
prove that those couples who thoroughly understood the process had a sense of being in control and had a higher rate
of achieving pregnancy. It is important that an exchange of
ideas takes place with the members of the fertility team. We
also encourage interaction with other couples who are also
going through the same process. Trying to hide the problem
of infertility leads to a greater stress for the couple.
Along with the medical treatment, it is also possible to
have psychological counseling with a physician specially
trained in psychosomatic medicine. This is recommended
either before or during treatment.
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Gynaecological infertility diagnostics
Sonographic appearance of the
endometrium during the second half
of the menstrual cycle (the so-called
luteal phase), during which the
endometrium becomes increasingly
homogeneous correlating with its
secretory function.
Sonographic appearance of a
normal endometrial structure with
the display of three parallel lines.
After the initial consultation we will discuss with you in depth
the next diagnostic steps to be taken. The goal of the diagnostic phase is to discover the cause of the infertility and to
discuss the prognosis and risks of the infertility treatment
as well as any possible complications and the prevention of
such during the pregnancy.
The main goal of the infertility diagnostics of the woman
is the monitoring of the different phases of the natural menstrual cycle. The menstrual cycle begins with the first day of
the period and usually lasts for 28 days. During this time the
maturation of the follicle occurs. The follicle releases one egg
and becomes the corpus luteum or yellow body of the ovary, which supports the implantation of the egg in the lining
of the uterus. The menstrual cycle ends after 28 days when
the next period begins. If the cycle is normal, the greater the
chance of a pregnancy. The menstrual cycle will be followed
through ultrasound and repeated blood specimens (drawing of blood). You will be kept informed of all of the different
steps through your physician.
Menstruation begins with the first day of normal bleeding. It is of no consequence if the bleeding begins in the
morning or night. You should call and make an appointment
for the necessary measures to be taken.
There are some women who experience spotting before
their period. This should not be confused with the actual start
of your period. These premenstrual spottings are caused by
discrete fluctuations of the hormones. The period is usually characterized by stronger bleeding. It is at this point that
you should call and make your appointment at the following
number: ++41 61 265 93 37.
During your first appointment (between the 3rd and 5th day
of the menstrual cycle), we will conduct those tests which
will yield the most information concerning your menstrual cycle. A blood test as well as an ultrasound examination
will tell us the size of your ovaries and the degree to which
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the pituitary gland is capable of stimulating your ovaries
to permit follicle maturation. In addition, we will be able to
assess whether or not it is really the start of your period or
just some spotting. The ratio of male to female hormones will
also be determined as well as whether or not abnormalities
of the maturation of the egg follicle are present. For example, an elevated secretion of prolactin or inadequate function
of your thyroid gland will be diagnosed through these tests.
These abnormalities can occur without you otherwise being
aware of them.
The next appointments will occur around the time of ovulation. The main aim here is to find out if the interplay of the
hormones occurs correctly so that a pregnancy can occur
naturally. As a rule: the more normal the cycle the greater
the chances of being able to become pregnant with a minimum of treatment.
The corpus luteum phase begins after ovulation and can
only be monitored through blood tests. The quality of the
corpus luteum cannot be judged through ultrasound. The
corpus luteum phase can be abnormal either in its length or
the quantity of hormone it produces. Therefore, it is important to draw blood on different days of this phase in order to
determine if sufficient production is present. If a pregnancy
does not occur then the corpus luteum will cease hormone
production and be reabsorbed by the body. With the cessation of this hormone production the next menstrual period
will begin.
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Electron microscopic image of the
surface of healthy endometrium
with the glands protruding into the
uterine cavity.
Examination of the uterus and the fallopian tubes
Benign polyps of the endometrium
are a common cause of infertility
and are found in approximately 5 %
of our patients.
Hysterosalpingographic of a normal
uterus also containing a few
air bubbles. The left fallopian tube
is occluded in the fimbrial
part, which is close to the ovary.
Irregularities of the endometrial lining of the uterus can be depicted accurately with a transvaginal ultrasound scan shortly before ovulation. It is also possible to diagnose polyps or
other conditions which can prevent a pregnancy from taking
place. Polyps are responsible for about 5 % of the cases of infertility in women. Should polyps be present then assessment
of their size and location are necessary as a next step.
This is achieved through hydrosonography (e.g. saline
infusion sonography), where a thin plastic tube is placed in
the cavity of the uterus through the cervical canal. The cavity
is then filled with sterile water. Together with ultrasound it is
possible to gain more information about the size of the polyp
and whether or not more than one polyp is present. This procedure causes only slight discomfort for the patient.
After having been diagnosed, the polyp can be removed
through a small operation. This is done through the use of a
hysteroscopy, the examination of the inner cavity of the uterus through a fiberoptic telescope inserted through the vagina
and the cervical canal. This is usually performed under general anesthesia or a spinal block. The neck of the uterus is first
dilated and then a fiber-optic telescope, which is connected
with a video camera, is placed in the cavity of the uterus. The
uterus is then filled with a clear fluid which helps to depict
the structures. This way the inner cavity can be seen on a
video screen in the operating room. Through an additional
fiber-optic device placed in the abdomen, fine instruments
can be introduced and used to treat or remove structures
which can hinder pregnancy.
The obstruction or lack there of in the fallopian tubes can
be assessed by the doctor and radiologist through the use of
hysterosalpingography (HSG). In using this method, a radioopaque dye is injected through the cervix into the uterus and
fallopian tubes. If the tubes are not blocked then one immediately sees the dye in the abdomen. This can sometimes be
painful, although a general anesthesia is not usually required.
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The advantages of this operation are that it is quick, relatively
easy to perform, and allows a good depiction of the uterus
and the fallopian tubes.
A laparoscopy is a surgical procedure in which a tiny
scope is inserted into the abdomen through a small incision.
It is used for a variety of procedures and often to diagnose
diseases of the fallopian tubes, ovaries, and pelvic cavity.
In order to increase visualization the abdomen is filled with
air before the operation begins. It is also possible to perform smaller operations such as adhesion removal, because
adhesions can hinder the movement of the fallopian tubes
when receiving the egg. Endometriosis, which is a condition where tissue strongly resembling the uterine mucous
membrane (endometrium) occurs in various locations in the
pelvic cavity, can be a cause of infertility. Through laparoscopy these conditions can be ruled out. Sometimes blockage of the fallopian tubes can also be treated surgically during laparoscopy.
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Sonographic image of a fallopian tube
filled with liquid. This situation
is termed hydrosalpinx and warrants
surgical treatment.
Preparation of the long desired pregnancy
Electron microscopic image of a spermatozoon.
On the top of the head is “visualized”
the acrosome, which is needed for the attachment of the spermatozoon to the outer layer of
the oocyte and its subsequent penetration.
Acrosome
After evaluation of the patient for the different causes of infertility and the assessment of the chances of a pregnancy, different tests are usually performed in order to avoid
early complications and risks during this period. For example, a determination of the patient’s immune status with regard to rubeola (German measles) is done, the blood group
is typed and the presence of antibodies is ascertained. Infections such as HIV, viral hepatitis B and C and syphilis must be
ruled out before beginning an infertility therapy. Ruling out
malfunction of the thyroid gland is also important.
Taking folic acid has been proved to reduce the rates of
malformation of the spinal column (e.g. spina bifida, hydrocephalus), which can lead to compression of the nerves of
the back and lead to paralysis of the child. The recommended daily dose is 0.4 mg of folic acid.
Normal semen
Spermatozoon without acrosoma
(globozoospermia)
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Causes of infertility in the male-examination of the male patient
The cause of infertility can also reside in the male partner. The
most important examination of the male is the analysis of his
semen in the spermatological laboratory. This test examines
the number, motility and form of the sperm in the ejaculate.
This should, however, not be the only diagnostic step undertaken. It can occur that a semen analysis gives severely
abnormal results, but the pregnancy is still possible. On the
other hand some couples, in whom the sperm count is normal, have long-standing difficulties achieving a pregnancy.
Therefore, it is important to conduct a full case history and
physical examination in order to accurately assess the health
status of the male patients. The main goals of the consultation and examination are
• to clarify whether or not the results of the tests are in
accord with the physical examination;
• to examine what the causes of the reduced potency are
and what methods are available to help the male patient
so that his partner can become pregnant spontaneously;
• to assess the psychological status of the patient with reference to the difficulties in conceiving.
The principal properties together with
their normal ranges of human semen
are listed below. These standards have
been established by the World Health
Organization (WHO).
Normal ranges of the examination of the ejaculate
Volume of the ejaculate
2 ml or more
Sperm concentration
at least 20 millions
per millilitre
Progressive mobility
≥ 50 %
Normal morphology
≥ 25 % normal
Velocity of sperm
100 micrometre per
second or more
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Ultrasound is an important diagnostic tool to assess the condition of the male genitalia. One is able to measure the volume of the testicles which can be evaluated together with
the results of the sperm count and blood tests. The physical
examination consists of an evaluation of the volume and consistency of the testicles where abnormalities can be a sign of
a past illness, and an examination to see if enlarged veins are
present in the scrotum, which is called varicocoele. In addition, the penis will be examined to see if malformations are
present such as abnormal placement of the urethra or if cysts
are present in the scrotum or epididymis.
The results of the physical examination are then compared to the results of the blood work in order to give a
comprehensive picture of the health of the male sexual organs. The sperm count results show only the condition of the
sperm at the moment. Considerable variation in the results
can be present over a longer period of time. Due to this fact
it is necessary to repeat the sperm count several times. We
recommend that the sperm count be performed two or three
times to make an accurate diagnosis.
It is very important for the sperm count to be done correctly in order for the results to be accurately interpreted. By
following certain recommendations, the results can usually
be improved.
The amount of time between sperm donation and analysis in the spermatological laboratory must be kept to a minimum. Due to this fact, the spermatological laboratory is located directly next to the room where the sample is produced. The sample is essentially an alkaline liquid which can
after some time become damaging to the sperm. Waiting too
long for analysis can cause the sperm to be damaged and the
result will then be pathological, hence the proximity of the
spermatological laboratory to the room, in which the semen
sample can be collected.
You will receive a sterile container in which to place the
sample in order to avoid bacterial contamination which can
negatively falsify the results.
It is important to pay attention to the following rules:
1. Avoid taking any medications before the sperm count.
Should it be absolutely necessary to take medications,
please inform us about the name and dose taken.
2. It is important to be abstinent two to seven days before
the analysis. Ideally, you should refrain from having an
ejaculation five days before the sperm count.
3. To avoid contamination, you should urinate and wash
your hands and penis before ejaculating. The urinating
reduces contamination of the urethra.
4. Please try to place the entire amount ejaculated in the collection vessel. If this is not possible, then be sure to tell
the laboratory assistant if some fluid could not be collected. The analysis will be adjusted accordingly.
5. Be sure to close the vessel properly and bring it immediately to the spermatological laboratory.
It is definitely not our goal to completely adapt your sex life
to the needs of reproductive medicine. These are just some
hints to ensure an accurate examination of your ejaculate.
Experience has shown that the greatest way of achieving
pregnancy is through constant sexual intercourse. We do
not recommend that you always wait five days before having sex with your partner.
The evaluation of the sperm count consists of determining the number of spermatozoa present in the seminal fluid
and assessing their motility and morphology (shape). After
evaluating just these three factors it is often possible to pinpoint the cause of infertility in a couple as well as to define
the origin of the infertility in the male partner.
In addition to a detailed case history, physical examination and microscopic evaluation of the sperm count, we will
perform some hormonal analyses on the blood. The following three important hormones will be tested: LH, FSH, and
testosterone. The test tubes with blood from this examination will be frozen for determination of values at a later time,
should the need arise. The blood work must be done between 7.00 und 9.00 in the morning because the values
change throughout the day. Evaluation at a later time can
lead to incorrect analysis.
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Important rules for the analysis of semen:
Asthenozoospermia The motility of the sperm is reduced:
less a 50 % of the sperm demonstrate normal motion.
Oligozoospermia The number of sperm in the ejaculate is
reduced: There are less a 20 million sperm in one millilitre
of ejaculate.
Teratozoospermia Less than 30 % of the sperm are of a normal shape. Malformations of the head, body and tail of the
sperm are possible.
Azoospermia There are no sperm in the ejaculate. The specimen is centrifuged and therefore concentrated in order to
insure that no sperm are present. This condition can occur
when no sperm are produced or through blockage in the
efferent ducts from the testicles.
Parvisemia The volume of the ejaculate is less than two millilitres. This may be caused by congestion of the prostate
gland or of the seminal vesicles. In this case, even when a
sufficient amount of sperm is available, this condition
inhibits the spontaneous transport of the sperm to the
fallopian tubes.
Varicocoele In this condition there are enlarged veins
around the testicles, more often on the left side. The same
mechanism leads to hemorrhoids and varicose veins and
is caused by faulty valves in the veins. This leads to a congestion of the blood in the vessels which then become
enlarged.
Hydrocoele This is a collection of watery fluid around the
testicle. This is usually a harmless condition but can sometimes be a sign of chronic infection in the genitals.
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Spermatocoele A spermatocoele is a benign cystic accumulation of sperm and fluid, often found in the head of the
epididymis, which can be the result of a previous infection
in the epididymis.
Conditions causing infertility and their consequences:
Tubal infertility Through the use of ultrasound, hysterosalpingography or laparoscopy blockage and other pathologies
of the fallopian tubes can be determined.
Male infertility The semen analysis determines whether
sperm quality is abnormal.
Immunicological infertility The male patient has antibodies
against his own sperm. This impedes the movement of the
sperm through the uterus as well as hinders the adhesion of
the sperm to the egg which, in turn, reduces the chance of
fertilization.
PCO-Syndrome In this condition, often found in obese
women who do not ovulate, the ovaries are characterized by
a distinctive pattern of excessive cysts in the ovaries. Hyperinsulinaemia, which can occur in both thin and obese women, can contribute to a higher risk of developing diabetes.
These women also have excessive body hair.
Incipient ovarian failure An elevated level of FSH is measured at the beginning of the menstrual cycle and is usually a
sign of a poor prognosis of fertility.
Pituitary/hypothalamic infertility Women with a negative
pituitary stimulation test (LHRH-test), or whose pituitary
gland was removed or who have hormonal abnormalities
in the hypothalamic region resulting in inactive pituitary, suffer from a lack of menstrual cycles, and, therefore, infertility.
Unexplained infertility When none of the conditions mentioned above has been identified to be the cause of infertility in a couple.
Endometriosis Growth of the lining of the uterus on other reproductive organs or other organs in the abdominal cavity. Approximately 6 to 12 % of all women suffer from this condition.
Symptoms include recurring pain in the abdomen during menstruation due to bleeding of the endometriosis. Typical locations include the fallopian tubes and peritoneum. The endometriosis on the fallopian tubes can also be a cause of infertility
because it can bleed and impair the function of the tubes.
Fibroids A benign tumor of the uterine muscle, a fibroid can
grow towards the outer margin of the uterus, but also towards the inner lining, so that it may interfere with the regular development of a pregnancy. Fibroids can also disturb the
blood supply of a pregnancy, even if they are located at some
distance from the embryo. However, often fibroids are a coincidental finding and treatment is not necessary.
Sonographic image of a polycystic ovary
(PCO), in which the follicles are pushed
to the periphery of the organ. The thick,
grey area in the centre of the organ marks
the tissue, in which the testosterone
is produced, which inhibits the growth
of the follicles.
25
26
Treating the causes of infertility themselves
Many of the conditions mentioned above can be treated in
such a way that a pregnancy can occur spontaneously. Directed treatment of these disorders is preferable to assisted fertilization, because they are much less intensive both
physically and emotionally. In addition, the complication rate
is much lower.
A few examples of common treatments of secondary conditions responsible for infertility:
• Antibiotic treatment of genital infections
• Medical therapy to lower abnormally elevated prolactin
levels
• Surgical opening of blocked fallopian tubes
• Treatment of malfunction of the thyroid gland
• Pulsatile treatment with LHRH infused with a portable
pump
• Weight reduction programs for adiposity
• Treatment of hypertension
• Surgical and hormonal treatment of endometriosis
• Surgical and hormonal treatment of fibroids
It is unfortunate that often the cause of infertility cannot be
treated successfully. This is frequently the case when the
condition has been present over a long period of time and
has become irreversible. For example, a varicocoele that remains untreated for many years causes slow but irreparable
damage to the testes. The reduction of the volume of the
testicles has usually already taken place by the time the infertility is diagnosed. Although a treatment of varicocoele is
available (e.g. surgical removal of the varicocoele), it is often
unsuccessful. Therefore, removal of the varicocoele at this
point rarely leads to normal conception.
27
There are many causes of sterility for which there is no effective treatment. This is true if cryptorchidy (e.g. undescended
testicles during early childhood) is not corrected. There are
no measures which can be taken to improve the quality of
the sperm, although the disturbance dates back many years.
In this situation one has to resort to assisted fertilization.
28
Methods of assisted fertilization
In conventional IVF the oocyte
remains surrounded by the coronal
granulosa cells, although the other
cells were removed by enzymes
on the surface of the spermatozoa.
Although by now the fertilizing
spermatozoon must have penetrated
the oocyte, the signs of fertilization
can not yet be seen.
The impact of the woman’s age on the result
of in vitro fertilization, which is
inversely correlated with the woman’s age.
Data from Templeton, Morris and
Parslow, The Lancet, 1996 (pp.1402–1406).
��
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1.
2.
3.
4.
intrauterine insemination (abbreviation AIH or IUI)
insemination with donor sperm (AID)
in vitro fertilization (IVF)
intracytoplasmatic sperm injection (ICSI)
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Three of the above-mentioned methods use the eggs and the
sperm of the couple, whereas in the second, AID, the sperm
is donated by a healthy volunteer.
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Assisted fertilization or artificial reproduction can be used
when the secondary causes of infertility cannot be treated directly or when treatment has failed. The major disadvantage
of assisted fertilization is that the cause of infertility is not corrected. One treats the symptom (e.g. involuntary childlessness) but not the disease underlying the infertility.
Conversely, the advantage of assisted fertilization is that it
is highly effective and offers a range of treatment options for
almost all infertile couples. If a couple remains childless for
years the chance of a spontaneous pregnancy drops to only 1
to 3 % every month, where as rates of 15 and 35 % per month
can be achieved through assisted fertilization. It must, however, be stated that these rates are highly individual and inversely correlated with the age of the female partner.
Numerous different forms of assisted fertilization have
been developed over time. However, four of the most clinically relevant methods are offered by the University Women’s
Hospital of Basel:
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1. Insemination is prepared by separating the most vigorous sperm out of the ejaculate. During intrauterine insemination (IUI) motile spermatozoa are inserted into the
uterine cavity, once before and once after ovulation.
These inseminations are done with a very thin flexible
tube so that the lining of the uterus is not damaged. The
goal of the procedure is to insure that a maximal number
29
of healthy sperm are placed in close proximity to the fallopian tubes. This is an ideal method when the mobility
of the sperm is suboptimal or the development of the egg
in the follicle is not normal. Insemination is not an appropriate treatment for couples suffering from severe seminal abnormalities.
2. In in vitro fertilization (IVF) the fertilization process takes
place outside the female body. The egg and spermatozoa are kept for a maximum of 48 hours in the laboratory of reproductive biology. The conditions in the culture
room closely resemble the environment of the fallopian
tubes. The penetration of the egg by the sperm is identical to the process which takes place in the fallopian tubes
of the women. After fertilization has been successful, the
embryo is replaced into the uterine cavity. Because the
passage of the egg through the fallopian tube is avoided,
this method is ideal for cases where the fallopian tubes
are blocked or do not function properly.
3. A viable spermatozoon is placed inside the egg during
intracytoplasmatic sperm injection (ISCI, also known
as microinsemination or microinjection). The egg and the
single spermatozoon are brought together through the
use of two very fine micropipettes made of pulled and
chiselled glass tubes. This is only possible when the egg
is harvested from the women’s body in the same manner
as in IVF. It is possible to bypass the penetration of the
egg by the sperm with this method and it is useful even
in cases with very low semen quality. Interference of the
actual process of fertilization (e.g. the merging of the egg
and sperm) does not take place, because the latter usually occurs approximately 24 hours later.
The process of intracytoplasmic
sperm injection (ICSI).
30
Swiss law on reproductive medicine
On the first of January 2001 a restrictive law regulating all
aspects of reproductive medicine was enacted. In Switzerland the main goal of this law was not only to offer to childless couples the right to seek medical help and treatment
but also to safeguard the rights of the unborn child. A high
priority is placed on providing patients with comprehensive
information concerning the different methods of conception
in order to help them make the appropriate choice for their
particular situation.
The following aspects of the reproduction law are important
for you to know:
• Adequate information must be given not only on assisted reproduction but also on adoption and psychological
counseling.
• Implementation of these methods accurs only when the
couple’s consent is available.
• Right to a second opinion concerning the choice of the
method is insured.
• The law allows for a consideration period of four weeks in
order for you to make a decision on a certain method before actually starting with the therapy.
• A maximum of three embryos may be replaced per treatment cycle in order to prevent high order multiple pregnancies.
• Cryopreservation of embryos is forbidden.
• Eggs in the pronucleate stage may be preserved for a period of up to 5 years after harvesting.
31
32
Stimulation of the ovarian function for assisted fertilization
During a natural menstrual cycle only one follicle matures by
ovulation. However, not every egg will be fertilized, and on
the average, only one in ten to fifteen fertilized eggs may lead
to a healthy pregnancy. Therefore, the probability of a successful treatment cycle of assisted fertilization without stimulation of the ovaries is quite modest (approximately 5 % in
unselected cases). In order to improve the chances of achieving pregnancy, the ovaries are now routinely stimulated
before performing assisted fertilization. The goal of this
intensive hormonal treatment is to increase the number of
follicles, to improve the quality and developmental potential
of the eggs enclosed in these follicles and to control the timing of follicular maturation. The most important advantage of
ovarian stimulation is that it increases the pregnancy rates
to 15 to 35 % depending on the method used and on the
age and general health of the patient. Not only IVF and ICSI
depend on ovarian stimulation, but also intrauterine insemination which was found to be ineffective without ovarian
stimulation. With intrauterine insemination pregnancy occurs
in only 3 % of all treatment trials, but with ovarian stimulation
the pregnancy rates rise to 15 to 22 %.
33
34
There are, however, various clearcut disadvantages
related to the ovarian stimulation
One of the major problems is that of multiple pregnancies.
Twinning occurs in 12 to 17 % of the treatment cycles, triplets
in about 1 to 3 %. High order multiple pregnancies (quadruplets and more) are extremely rare and are not expected during treatment in the University Women’s Hospital of Basel.
In addition to multiple pregnancies there is the problem
of an overreaction of the ovaries to the hormonal stimulation. this may lead to Ovarian Hyperstimulation Syndrome,
the second most common complication of assisted fertilization, particularly of IVF and ICSI. When the ovaries enter
hyperstimulation syndrome, they become extremely swollen (reaching a diameter of 10 cm or more each). These enlarged ovaries produce transsudation in all blood vessels and
this leads to general edema, particularly in the peritoneal cavity (e.g. ascites). In extreme cases, this may lead to circulatory collapse, renal failure and even death. These symptoms
usually occur at the beginning of a pregnancy (through the
effects of the pregnancy hormone, HCG). Some women
carry an increased risk of suffering from this complication, a
risk which can usually be identified before treatment. When
the ovarian hyperstimulation syndrome (OHSS) occurs, it
is sometimes recommended to hospitalize the patient. To
the same extent the hyperstimulation can be prevented or,
if it occurs, be reduced in severity. In the event the patient
has conceived, having OHSS may be associated with a higher risk of miscarriage, but it does not usually endanger the
health of the baby later in pregnancy.
There has been some discussion concerning whether or
not having undergone ovarian stimulation leads to a higher
rate of ovarian cancer. At present, there has been no conclusive evidence to support this theory. However, it is known
that some types of infertility are associated with a higher incidence of ovarian cancer. Although the association between
ovarian stimulation and cancer has not been proven, it is in
the interest of the patient to keep the number low.
35
Treatment with the “long protocol”
IVF and ICSI are most commonly treatment with a protocol
for ovarian stimulation called “long protocol”. This treatment
involves the use of gonadotropin releasing hormone-agonist
(GnRH-agonist) which suppresses the production of the gonadotropins LH and FSH in the pituitary gland for 4 to 6 weeks.
Through this single injection suppression of the pituitary gland
hormones is achieved to stop these from competing with the
artificially administered ones. This is done to be better able to
control the hormonal stimulation of the ovaries. In addition,
the risk of premature discontinuation of the treatment is considerably reduced through the administration of the long acting GnRH-agonist. When the ovaries are no longer directly
under control of the pituitary gland it is easier to stimulate a
greater number of follicles. As a consequence there is a higher rate of achieving pregnancy but there is also a higher incidence of Ovarian Hyperstimulation Syndrome (OHSS).
The preparatory treatment with a long-acting GnRHagonist may be associated with some side effects such
as sweating, hot flashes, depression and other symptoms. This is because the body suffers from too little estrogen from the time interval between the menstruation occurring after the injection of the GnRH-agonist and
the start of ovarian stimulation. These symptoms usually resolve rapidly after the initial growth of the ovarian
follicles. Furthermore, there is sometimes a slight and temporary weight gain.
The GnRH-agonist must be administered approximately
between the 20th and 25th day of the menstrual cycle or just
after the commencement of menstruation. It takes about 14
days until the full effect of the medication is reached at which
time the stimulation will begin. A blood sample is then taken to
confirm that the ovaries are no longer secreting hormones into the bloodstream. This is the treatment of choice for patients
who do not have normally functioning ovaries or who suffer
from the PCO-syndrome or endometrial cysts in the ovaries.
36
Treatment with the “short protocol”
When the maturation of the follicles is normal, stimulation
can also be performed without simultaneously blocking
ovarian production of hormones. In order to avoid ovulation
before sufficient maturation of the follicles, it is then necessary to block the signal which leads to ovulation at the end
of the follicular maturation with another drug, the GnRH-antagonist. In contrast to the GnRH-agonist, the GnRH-antagonist becomes active immediately after its administration. This
protocol is called the “short protocol” in which the hormonal
production of the ovaries is not suppressed before the start
of the actual hyperstimulation of the ovaries. Instead of this
preparatory injection, additional injections with a GnRH-antagonist must be given at the end of the maturation of the
follicles. Therefore, according to this protocol, two daily injections must be given over a period of several days.
It is imperative that the therapy begins on the 2nd day of
menstruation and is, therefore, not the therapy of choice for
women with irregular menstruations. This type of stimulation
is mostly used for women with ovarian insufficiency or under special conditions.
The advantages of the “short protocol” as opposed to the
“long protocol” are the shorter duration of treatment as well
as the smaller amount of exogenous hormones that have to
be administered. In addition, there is a reduced incidence of
OHSS through the lower number of follicles growing. The
major disadvantages are the lower number of oocytes recovered and the difficulty in scheduling the treatment. Therefore,
with the short protocol the number of pronucleate oocytes
available for cryopreservation is usually lower.
37
Prof. Dr. med. Ch. De Geyter
Division chief
Dr. rer. nat. M. De Geyter
Head of laboratory
Dr. med. S. Steimann, senior physician
during the telephone consultation
38
Details about the stimulation of the ovaries
In the natural menstrual cycle only one follicle matures up to
the final stages of follicular development and ovulates.
Observation has revealed that all methods of assisted fertilization with only one naturally matured egg result in very low
pregnancy rates. It has been demonstrated by the long standing experience acquired with assisted reproductive medicine
today that all treatment methods are more effective when a
larger number of matured eggs are available for fertilization.
For example, only 3 follicles are necessary for intrauterine insemination, however, it is advantageous to have at least 5 to 8
eggs (oocytes) available for IVF und ICSI.
The disadvantages of the ovarian stimulation are the high
costs and the close monitoring necessary. Repeated blood
work and ultrasound examinations both during the week and
on weekends and holidays have to be done. The number and
the size of the follicles have to be controlled sonographically.
The results of the tests must be evaluated on the same day in
order to determine what dose of the medication is appropriate. The hormone injections can now be administered subcutaneously so that patients themselves can take an active part in
their therapy and the visits to the hospital can be reduced.
In the University Women’s Hospital of Basel the treatments
are organized as follows: The blood work and ultrasound examinations take place between 7.00 and 9.00 am. In the afternoons the cases are evaluated and the patients can call the
following telephone number (++41 61 265 93 37) in order to
find out about the exact dose of the medication they should
receive. The injection must take place precisely between 4.00
and 5.00 pm. Be sure to administer the correct amount of hormone.
39
Sonographic image of a follicle
shortly before ovulation. The
colour marks those blood vessels,
which arise around the follicle at
the end of follicular maturation.
40
Triggering injection for ovulation induction
When the follicle has reached maturity (18 to 22 mm in diameter) it is time to prepare the follicles and the oocytes
for the follicular aspiration or insemination. An injection of
pregnancy hormone (human chorionic gonadotropin, HCG)
is essential for this purpose. It is imperative that these injections are administered exactly on time. If delays occur, it can
interfere with the treatment of other patients. The harvest of
the oocytes must take place exactly 35 hours after the trigger injection.
41
42
Aspiration of the follicular content for oocyte retrieval
At the moment of oocyte collection,
the latter is still surrounded by the
corona radiate (the dense layer close
to the central oocyte) and by the
cumulus oophorus, the loose complex
of cells at greater distance of the
oocyte. This whole complex may have
a diameter of several millimetres..
Ultrasound-guided transvaginal follicle aspiration is the
method used for the retrieval of the egg in both IVF and ICSI.
The transvaginal follicle aspiration is done on an outpatient
basis and either pain medication or general anesthesia can
be administered according the wishes of the patient. In all
cases the patient is not allowed to eat or drink in the morning
of the follicle puncture (that means nothing to eat or drink
starting at midnight). Urine should be voided just before the
procedure. The partner can be present during the procedure.
On a screen, which is connected to the microscopes, both
the patient and her husband can follow the identification and
the manipulation of the eggs in the laboratory of reproductive biology next door.
Retrieval of the egg is performed through the use of a
hollow tube placed in the vagina and guided by ultrasound.
This insures an accurate aspiration of the follicular content.
The ovaries are located just behind the posterior vault of the
vagina so that it is not necessary to penetrate deep into the
body. The content of the follicle, which includes the egg,
some nourishing cells (e.g. granulose) and follicular fluid are
then removed through the needle under controlled continuous pressure. Should the egg still be attached to the follicular wall, it can be freed through repeated flushings with sterile culture medium. In order to be able to collect all available oocytes, the surgeon communicates constantly with the
biologist in the laboratory next door.
This type of follicular aspiration is also used to reduce
the number of follicles before an intrauterine insemination,
so that a higher order multiple pregnancy can be avoided
without having to cancel the cycle. All of the smaller follicles
are retrieved and discarded prior to ovulation and insemination so that only three remain. This is the maximal number
allowed. The procedure lasts for only a few minutes and
usually does not require any anesthesia. Two hours after the procedure the insemination will take place. Years
43
of experience have show that the chances of achieving
pregnancy are not diminished and the rate of multiple pregnancy is reduced.
A complication that can occur is damage to organs in the
vicinity of the puncture such as the intestines or blood vessels. Extremely rarely surgical repair may have to be done
after the puncture. In order to identify potential complications, we prefer you to remain under observation in the hospital for two hours after the procedure.
44
Semen collection and the preparation of the
spermatozoa for assisted fertilization
In most cases, the male partner must render a semen sample
through masturbation on the same day of the egg collection.
There is a specially designated room for this purpose (the so
called “Z room”). This is located in a quiet and discrete area
of the clinic so that you will not be disturbed.
You will be told at what time you need to donate sperm
as soon as possible in advance. Normally this occurs on the
morning of the oocyte collection. It is not crucial at exactly
what time the specimen is attained only that it be available
the same day as the follicle aspiration or insemination. We
recommend abstaining from ejaculation no more than 7 days
and no less than 2 days before the procedure.
If you are afraid of encountering some psychological
blockage producing the semen on the day scheduled, please
tell us in advance. It is always possible to collect the semen
on a preceding day or to store the semen frozen.
The semen is then prepared (also called “sperm washing”) in order to separate the viable spermatozoa both from
the non-viable ones and also from the surrounding seminal
fluid. The ejaculate is first mixed with a delicately prepared
culture medium, then placed in a centrifuge and then the
overlying fluid is removed. Then a small amount of the culture medium is again gently added to the sperm so that the
viable sperm can swim up into the overlying fluid. Only the
most vigorous spermatozoa are able to achieve this. After
about an hour this fluid, which contains 80 to 100 % of motile spermatozoa, can be used for the fertilization process.
The whole procedure lasts for about 2 to 3 hours and is usually done before and during the follicular aspiration as a matter of convenience.
45
46
Aiding the implantation of the embryo through “assisted hatching”
It has been noted in several treatment centres that opening
the outer layers of the egg membrane (e.g. zona pellucida)
before the embryo transfer may facilitate the implantation of
some embryos. An increased rate of implantation has been
seen in older women and in those who have an especially
thick egg membrane. Our unit is equipped with a special system capable of boring a small hole with a fine laser beam into
the egg membrane (e.g. zona pellucida) without endangering
the embryo. Because the method is both rapid and easy to
perform and because the benefit in single patients can not
be identified easily, we apply this technique on all embryos in
order to increase the probability of their implantation.
The arrow marks the opening
into the zona pellucida made by
a laser beam.
47
48
Replacement of the fertilized egg into the uterine cavity
Oocytes in the pronucleate stage.
The pronuclei characterize the
stages of the development just prior
to actual fertilization, in which the
male and the female nuclei finally
merge. In this stage the oocytes can
be stored frozen.
The fertilization takes place several hours after retrieval of
the egg. On the following day we will tell you, whether fertilization has indeed taken place. The most crucial phase of
the fertilization can be made visible under an inverted microscope: the pronucleate stage.
It sometimes occurs that two spermatozoa penetrate the
egg simultaneously or that the nucleus of the egg doubles
during the process of fertilization. The consequence of these
errors are triploid embryos, which are not viable and cannot
be replaced.
Two days after the egg retrieval up to three of the fertilized eggs are replaced in the uterine cavity. This procedure is
similar to a normal gynaecological examination, but requires
the patient to come with a full bladder. The full bladder facilitates the visualization of the uterus. The embryos are deposited through a fine hollow tube into the uterus. This process
is guided by a transabdominal ultrasound scan.
The implantation of the embryo in the lining of the uterus takes place some days later. The most common reason
for not becoming pregnant is the failure of the embryo to
implant.
In order not to endanger the embryo, it is not possible to
use disinfectant on this area so an infection is, theoretically, possible. However, this occurs very rarely. Nevertheless,
please be careful to note if you should have fever or abdominal pain during the days following the embryo transfer.
Two embryos in the four cell stage.
49
50
Yellow body or luteal phase of the cycle
Sonographic appearance of the yellow
body (corpus luteum), which results from
the ovulated ovarian follicle and
which produces the progesterone, which
is necessary to support the implantation
of the embryo.
It is during this phase of the menstrual cycle that the implantation of the embryo may take place. This usually happens
5 days after insemination or after the embryo replacement.
In order to increase the probability of implantation, progesterone is given as a vaginal suppository.
The ovaries may become enlarged as a consequence
of the ovarian stimulation during the first half of the cycle.
Therefore, some women feel somewhat bloated, may have
pain and suffer from constipation. The ovaries are somewhat vulnerable to injury at this time and it is important to
avoid excessive physical activity. On the other hand, the rate
of pregnancy is not appreciably increased, when the woman remains in bed. Luckily, most women do not experience
any symptom at all during the last days before the pregnancy test.
The psychological as well as the physical stress can
place an enormous burden on the patients involved, particularly during this phase of the treatment. The uncertainty of whether or not pregnancy has taken place poses the
biggest problem for most of the women. Asking questions
frequently and receiving continuous counseling from the
medical and the nursing team can help to overcome some
of these problems.
The pregnancy can be confirmed by a blood test at the
earliest 12 days after the embryo transfer or 14 days after insemination. Please note that a pregnancy can only be confirmed when the level HCG reaches 100 international units
per litre or more. An occasional false positive pregnancy test,
in urine testing, may be caused by some of the medication
given during the treatment. Therefore, a urine test should
not be performed.
51
52
Cryopreservation of supernumerary oocytes in the pronucleate stage
Oocyte in the pronucleate stage
of development. In this stage,
these oocytes can be cryopreserved and stored over a period
of up to 5 years.
If during the treatment with IVF or ICSI more than two or
three eggs enter the pronucleate stage, these can be preserved through freezing in liquid nitrogen. Deep-freezing
and preservation of eggs in this stage is called “cryopreservation of oocytes in the pronucleate stage”. These eggs can
be transferred to the uterus at a later time if required. This option allows the treatment team to place a smaller number of
embryos per cycle in order to avoid higher risks of multiple
births. If a treatment with IVF or ICSI should be unsuccessful, then a replacement of thawed oocytes in the pronucleate
stage into the uterine cavity can be performed without the
need of another ovarian stimulation nor oocyte collection.
Replacement of eggs that have been cryopreserved and
thawed in the pronucleate can occur in the uterus without
the patient having to undergo ovarian stimulation with gonadotropins. In this case the embryo transfer, depending on
the situation, will be performed in an untreated cycle or after
treatment with clomiphene citrate, with which the adequacy
of the luteal phase can be ensured. However, the success rate
is somewhat lower than that in the stimulated cycle, in which
the most viable freshly collected oocytes were collected,
fertilized and replaced. The replacement of cryopreserved
and thawed oocytes in the pronucleate stage lead to a pregnancy rate of around 20 to 25 % per trial.
According to legal restrictions, the eggs in the pronucleate stage can be preserved for up to 5 years after retrieval. Please let us know on a yearly basis if you still want to
keep the eggs preserved. After 5 years the eggs will be destroyed.
Plastic tube, in which the
oocytes are stored frozen.
53
Unsuccessful treatment
It is a high priority for us to inform you of the results of the
treatment before commencement of your period. Even if the
result is initially negative, there is still a small chance that you
are pregnant. Should your menstruation be late for more than
a week after pregnancy test, please call us so that we can
conduct another pregnancy test.
Should you not become pregnant after having undergone
an intensive fertility treatment it should be clear to you that
this is also a consequence of the natural course of reproductive nature. Considering that only 10 to 15 % of all fertilized
eggs lead to an intact pregnancy spontaneously, you should
not be unduly disappointed if you do not become pregnant
the first time. Should the first treatment fail, please do not become discouraged or seek reasons for the failure within yourself. Consider this to be an acceptable risk of the therapy.
In the event that a pregnancy did not occur, the ensuing
menstruation is usually more intensive than normal. Sometimes the entire lining of the uterus is shed and is accompanied by strong pain. This is called a “membranous menstruation”. This should not be confused with an abortion.
The following menstruation may be somewhat delayed
and after a long protocol therapy it can last occasionally as
long as 6 to 8 weeks. There is no special treatment needed.
54
Pregnancy
Depending on the age and physical condition of the patient
and the type of infertility treatment, pregnancy rates between
15 to 35 % are achieved. However, the live-birth rates are
lower, because miscarriages may occur. One has to make a
distinction between a biochemical pregnancy that can only
be confirmed through blood tests and a pregnancy that can
also be visualized with ultrasound.
We advise close monitoring of the developing pregnancy from the beginning of the pregnancy up until the 12th
week, after which a miscarriage is very rare. Until the 12th
week of pregnancy the rate of spontaneous miscarriage varies between 15 to 25 %. Furthermore, it is important to verify
whether the pregnancy is indeed located in the uterus (and
not in the fallopian tube) and whether it is a single or multiple pregnancy.
Folic acid is given prophylactically to reduce the risk of
neural tube defects (spina bifida, hydrocephaly). The optimal
dose is 0.4 mg daily and should be taken until the end of the
12th week of pregnancy.
The probability of embryonic deformations occurring after infertility is slightly higher than in pregnancies occurring
spontaneously without infertility. If desired, we offer comprehensive prenatal diagnostics to all patients. The counseling,
together with the genetic tests, will help you to learn whether or not there is an elevated risk of malformations. However, you should only have these tests performed if the presence of some embryonic or fetal malformation would induce
you to take active measures, such as termination of the pregnancy.
Since the introduction of ICSI there have been investigations of whether or not this method is associated with a
higher risk of deformations. It has, however, been proven
that there is not a higher rate of deformation (2.3 %) than
in a spontaneous pregnancy (about 2 to 3 %). There has
been a higher rate of sex-linked chromosome abnormalities
55
56
in children after ICSI. Taking into account that severe male
infertility is partially caused by genetic disorders and that
some of these disorders are coded on the Y-chromosome,
it is possible that through the use of ICSI these genetic abnormalities will be passed on to the male child. As a consequence of this, these individuals may suffer from infertility
during later life too.
After confirmation of the pregnancy your further care can
be done through your own gynaecologist starting from the
12th week. Our experience has shown that every pregnancy
achieved through assisted fertilization must be considered
to be a high-risk pregnancy and, therefore, must be closely
monitored during the pregnancy.
57
Conclusion
Of course, not all of your questions will be answered by
reading just one booklet. Our information booklet is not
meant to be a substitute for one or more extensive discussions with your physician, the nurse or the reproductive
biologist. This text is designed to help you formulate your
questions concerning the results of the dragnosis and treatment. A patient who is well informed will gain confidence in
our care and will be more satisfied with the treatment; we,
in turn, will achieve a better outcome.
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Counseling and psychological advice
Infertility poses a great dilemma for a couple desiring children. A solution to this problem is to seek help concerning assisted fertilization. It is our experience that treatment
should not only involve the infertility methods themselves
but also psychological counseling.
1. Infertility can cause a psychological crisis for a couple.
Men and women react differently to the diagnosis of infertility. There are many reasons and motivations for wanting a child. It is important to discuss the expectations of
both partners during the infertility treatment. This helps
the couple to cope with all the difficulties encountered
during therapy.
2. Both psychological and physical factors play an important
role in causing infertility. Learning to deal with psychological issues can improve the chances of conceiving a child.
To have a good look at these conflicts can lead to a better
understanding of problems in all aspects of daily life and
can improve quality of life in general.
3. Going through the process of evaluation in the infertility unit can create extreme emotional reactions: insecurity, fear, disappointment, feelings of shame, etc. These
stressful feelings not only increase the psychological burden but can also have an effect on the outcome of the
infertility treatment. For this reason it is important for us to
discuss these feelings in the hope of reducing the psychological strain on the patient and of increasing the chances
of successful fertility treatment.
4. In 40 to 50 % of all cases no defined cause of infertility can
be detected or the treatment is unsuccessful. This does
not mean, however, that your treatment with us is at an
end. It is one of our priorities to guide you further in your
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quest for a child. Options concerning adoption or psychological support in coping with definitive infertility are offered at the clinic.
For the reasons mentioned above, we offer comprehensive
counseling to all infertile couples. Dr. Tschudin, a specially
trained physician is available to evaluate the potential psychological stressors and to offer help in dealing with these
problems.
Prof. Dr. med. J. Bitzer
Dr. Tschudin
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Treatment of international patients
Many patients travel from outside of Switzerland to
University Hospital Basel reproductive specialists to
seek infertility treatment. UHBS has an international
reputation for providing the most advanced, effective
fertility treatments in a compassionate, patient-centred
environment. To fully satisfy the requirements of international patients, the hospital has created International
Services. This is a full-service department dedicated to
meeting the needs of international patients who receive their care at our hospital.
At our department of International Services, we co-ordinate
every aspect of the international patient‘s care, before, during and after their visit to our hospital. Our wide range of special services is designed to help international patients and
families to feel comfortable, pleasant and stress-free during
their stay. Our personalized approach to service includes
• Appointment scheduling with UHBS physicians
• Pre-registration and co-ordination of the admission
process
• Support for the medical visa application by working with
the Swiss embassies or consulates in your country
• Co-ordination of all appointments within the hospital and
between the clinics, laboratories and institutes
• Personal escorts to appointments and specialized
procedures
• Financial and billing arrangements including fixed price
offer in advance
• Translation services in several languages
• Special meals that honor dietary requirements
• Phone and internet lines in patient rooms
• Transportation arrangements including airport pickup and
ground or air ambulance services
• Hotel arrangements for patients and their families
If you have any further questions or want to make an appointment, do not hesitate to contact us:
University Hospital Basel
Department of International Services
Hebelstrasse 32, CH-4031 Basel
Switzerland
Phone ++41 61 265 31 10
Fax ++41 61 265 26 50
[email protected]
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Infertility unit
of the University Women’s Hospital Basel
Spitalstrasse 21
CH-4031 Basel
Phone ++41 (0)61 265 93 37
E-mail: [email protected]
Acknowledgements
This text was translated from German to English by
Dr. L. Herberich, Basel, and P. Ferrier, Münster, Germany.
Impressum
Design:
Schaffner & Conzelmann, Basel, Switzerland
Text:
University Women’s Hospital Basel
Photography: University Women’s Hospital Basel, Urs Flury,
Schaffner & Conzelmann