In-vitro fertilization (IVF)

In vitro fertilization means fertilization outside of the body. The female partner receives external hormones so that more follicles form in the ovaries. The egg cells grow within these follicles. Eventually, they are removed from the follicles and united with the partner’s sperm cells under laboratory conditions. Therefore, the fertilization occurs outside of the organism. After the embryos have developed to a multicellular stage they are implanted (maximum 2 to 3 embryos) into the uterus where they continue to develop.

 

The in-vitro fertilization treatment consists of several steps:

In order to increase the rate of success, the ovaries are stimulated with hormones. For this purpose, a treatment with injections is necessary to increase the development of ovarian follicles. Several factors determine what kind of medications will be used and at which dose: age, weight, smoker / non-smoker, previous surgeries on the ovaries, …

How long is the treatment?

The treatment with injections usually lasts 9 to 16 days on average depending on the stimulation protocol and how responsive you are to it. During this period, you will need to administer one to two injections s.c. (beneath the skin) on a daily basis. In rare cases you will need three or more. Thanks to modern injection appliances you can easily do this at home.

Hormonelle Stimulation Stimmedis

The ovaries’ reaction to this treatment is monitored by ultrasound examinations. We would like to point out that there are large differences concerning the ovaries’ reaction to the stimulation. The medication and its applied dosage are selected individually and with great care. Nevertheless, problems with stimulation might occur.

In order to achieve the last phases in the egg cell maturation process, a special injection has to be applied 34 to 37 hours prior to the collection of egg cells. In case the patient accidentally delays injection for several hours or even a day: We need to be informed as otherwise it might not be possible to collect any egg cells. Therefore, we need to be informed of this mishap prior to the beginning of the ovum pick-up.

Auslösen Eisprung
What kind of problems can occur during this phase of the treatment?
Through stimulation of multiple ovarian follicles it can lead to the hypophysis releasing the body’s own signal for ovulation too early, meaning the ovarian follicles could burst.
In order to avoid this special medicines are used. This means a premature ovulation can be prevented with high certainty, however not with a 100% guarantee! Our Institute cannot be held liable for an absence of ovulation, even if this absence is only identified during the ovum pick-up. Even if the injection took place at the correct time and a premature ovulation did not occur: we cannot guarantee that we will be able to find egg cells during the procedure or that these egg cells are suitable for fertilization.

We need the partner’s sperm sample on the day of the egg cell removal. This day can only be determined two days ahead of time depending on how the ovaries react to the hormonal stimulation. Some stimulation schemes can predict the calendar week in advance. Hence, it is of great importance to adjust vacations or business trips to the treatment. The partner can deliver his sperm sample directly at the Kinderwunschzentrum or bring it from home if the arrival is possible within an hour of the delivery.

What else needs to be considered for semen collection?

  • there should be no ejaculation 3-5 days prior to delivery
  • the bladder should be empty before semen collection
  • hands and penis need to be washed before the delivery

Samenabgabe

Which topics should be discussed ahead of time?

Problems with the semen delivery: If you have erectile problems or difficulties delivering a sperm sample through masturbation it is essential for our centre to know this the day BEFORE the egg cell collection takes place. There is no need to hide this problem or be ashamed as several alternative opportunities exist. Naturally the woman can accompany her partner during semen collection, or the man can bring the sample from home. Further, there is also the possibility to freeze a sperm sample at an earlier point in time. Please note that this procedure includes an extra fee.

Submission at home / in a hotel: If for some reason it is not possible to gain an ejaculate at the Kinderwunschzentrum the sample can be brought from home. You need to consider that the duration of transportation cannot exceed 60 minutes. It is crucial that the semen is not exposed to temperature fluctuations. Hence, it makes sense to carry it near the body. We always provide our patients with an appropriate, sterile container for this purpose.

Submission in a condom (no masturbation): In exceptional cases the usage of condoms is possible. Special condoms are necessary which can be obtained at our centre. Conventional condoms are laminated on the inside with a substance that can damage the sperm cell’s mobility and thus are NOT suitable for this purpose.

Not available on the day of puncture: If a semen delivery on the day of the egg cell collection is not possible this can be arranged for an earlier point in time. The sperm cells will be stored in a frozen state after an analysis of their quality and are thawed on the day of the ovum pick-up. If the quality of the sperm cells is poor cryopreservation is not advised – nevertheless, we will discuss this issue on an individual basis. We want to point out that cryopreservation will generate additional costs.

Usually, one egg cell develops in each follicle. Due to the growth of the follicle, the egg cell matures and is prepared for fertilization. If the stimulation leads to the development of sufficient and suitably sized follicles, the day of the so called “follicle puncture” can be defined. This procedure can occur under light anaesthesia. Normally, a sedation analgesia is conducted in order to avoid pain.

Procedure of ovum pick-up:
Under ultrasound guidance, the edge of a cannula is pushed through the septum directly into the follicles. During this operation not the follicle itself is extracted from the body but the fluid content of the follicle. Using this liquid the egg cell is rinsed into a specially preheated tube. In the laboratory, embryologists locate the egg cell within this liquid. At this point in time the egg cells are covered in a secure cell cluster, the so-called „Cumulus”.

The basic steps for the fertilization of the ovum are: The egg cell has completed essential steps towards maturing in the hours before the extraction (meiosis). This is important in order to have the right amount of chromosomes (carriers of genetic information) while waiting for the sperm cell. This phase is known as metaphase II.

IMPORTANT: Only an egg cell which has reached metaphase II can be fertilized! This phase will not be reached by all collected egg cells!

What methods for fertilization exist?

A) The traditional technique of In-vitro Fertilization (IVF)

Following the semen collection the sample is specially prepared in order to quickly isolate all the fast moving sperm cells and to make them “ready” for fertilization. At the end of this procedure they are placed in a special culture medium. The egg cells are located in a small bowl within the same medium. A drop of the sperm cell liquid is added to the egg cells. Independently, the sperm cells find their way towards the egg cells. In most cases, one sperm cell succeeds in fertilizing an egg cell. This technique can be applied if there is a sufficient amount of fast moving sperm cells with a normal external structure present within the sample.
Afterwards, it is possible to identify the first and second “polar bodies” on the egg cell and in the middle of the egg cell the two so called “pronuclei”. This can make it more difficult to tell if the fertilization was successful. Hence, it is better to wait one more day: often a regular embryo develops.

B) The intracytoplasmic sperm injection (ICSI)

If there are not enough fast moving and normally structured sperm cells available, a fertilization via ICSI is offered. A sperm cell is injected into the egg cell via a micropipette. IMPORTANT: Even if the sperm cells feature all the above mentioned characteristics and therefore no complications are expected, it might still happen that just a few or no egg cell is fertilized. This might be due to the egg cells’ quality or the sperm cells suffer from a malfuntion that cannot be identified with contemporary techniques.
IMPORTANT: Please understand that we are not able to formulate a distinctive statement for some egg cells the day after the puncture.

A fertilized ovocyte normally continues to develop further into an embryo. On the 2nd day, respectively 48 hours after the fertilization, embryos find themselves in a multi-cell state for the first time. These observations help our lab team to find the most suitable embryos for transfer.

IMPORTANT: This differentiation must not be taken for granted! In some cases, a pregnancy does not result even though regularly divided embryos were used. On the other hand, conceiving can be possible even if the embryos were divided irregularly.

All these development steps take place within the shell (zona pellucida). On the subsequent days the embryo divides further and ideally passes through the following phases:

  • Day 3 (72 hours after pick-up or ovulation): 6th to 10th cell phase
  • Day 4 (96 hours): Morula = Mulberry
  • Day 5 (120 hours): Blastocyst phase

The blastocyst phase:

On the fifth day of development the embryo in its blastocyst – phase begins to show signs of leaving the outer shell. Even the human embryo needs to hatch otherwise the blastocyst cannot make contact with the endometrium.

Embryo culture

Is the blastocyst culture the best form of treatment?

In principle, embryos do not feel quite as comfortable within the artificial culture mediums as they do in the uterus or the uterine tube. Thus it is very important to only cultivate embryos for 5 days if this method promises a better selection.

Please note that not all couples may derive a benefit from using the blastocyst culture. This technique is only advantageous if there are a lot of embryos!

IMPORTANT:

Should it be obvious after just two or three days which embryos have developed best, it makes more sense to undergo the transfer on the earlier day to spare embryos an unnecessary stay within the artificial culture medium and incubator.

Embryo transfer on the fifth day:
If more than one egg cell is fertilized and several embryos develop well it will be difficult to choose the best embryos after just two to three days. In such cases, it is better to wait longer, because on the 4th or 5th day it is possible to identify the embryos that developed best – in other words: to perform a “blastocyst culture”.

The transfer of one or more embryos into the uterus, the so called „embryo transfer“, is a key process of the IVF treatment. The decision how many embryos should be re-implanted into the uterus is one of great importance.

What should be considered during decision-making?

We recommend you carefully consider whether you would like one or two embryos implanted. It goes without saying that a final decision is possible only after we have informed you of the amount of fertilized egg cells, how many embryos developed, and of what quality they are.

Please consider a transfer of one embryo if
1) you are younger than 37,
2) it is your first or second attempt,
3) your embryos have developed well or
4) it is possible to freeze three or more additional embryos for a further attempt.

Please consider the transfer of an embryo if
1) you already have a child,
2) you already gave birth to twins,
3) you bear a higher risk for ovarian hyperstimulation syndrome,
4) you already had surgery on the uterus (e.g. myoma removal) or you have a basic illness (e.g. diabetes mellitus)

In individual cases you can decide for two or more embryos to be implanted. This can be taken into consideration after two or more failed IVF attempts or if you are older (> 40). You have to be aware that even with a bad prognosis a multiple pregnancy is still possible (with all implied risks).

What are the risks of a multiple pregnancy?

On average, twins are born two weeks and triplets six weeks too early. Compared to “IVF one-child pregnancies”, some distinctive elements were discovered for “IVF-twins”*:

  • they are born before nine months
  • they weigh less than newborns
  • they are more likely to be born by caesarean section
  • a treatment in the childrens intensive care unit is more likely
  • they stay longer in intensive care

* based on the results of two major Danish studies.

These differences are even more significant for pregnancies with triplets!
Pregnancies with twins or triplets are a huge burden for expecting mothers. Most likely she must will have to leave her job earlier and will have to undergo more regular check-ups during pregnancy.

In some IVF cycles where a high amount of embryos are obtained, there are still some left in the culture medium which indeed may lead to a pregnancy. In such cases it is possible to freeze these embryos in order to thaw them at a later stage for another attempt.

Is it possible to freeze embryos in each treatment cycle?

No. To enable a promising treatment cycle with frozen embryos there should be three or more frozen embryos available. It does not make sense to freeze only one or two embryos or to store embryos not showing an adequate developmental stage. Please decide in advance whether you would like to keep frozen embryos (if a sufficient number of top quality embryos remain after the embryo transfer) by signing at the end of the informed consent. We will inform you on the day of the embryo transfer whether the number and quality of embryos enable cryopreservation. In rare cycles we have to wait another 2 to 3 days until you can be informed.

How do the embryos develop after thawing?

Not all embryos achieve sufficient developmental potential after the thawing procedure. Therefore, it can happen that although embryos have been frozen it is not possible to perform the cryo transfer.
The embryos are stored in straws and because of methodological reasons we fill the straws with two or three embryos at a time.

 Kryokonservierung

A blood test 12 to 14 days after the embryo transfer shows if a pregnancy was achieved.

IMPORTANT: A successful IVF treatment correlates with a high number of different factors such as number of egg cells, fertilization and nidation.

Relationship between follicle and egg cells:
Basis for the treatment is the amount of follicles that developed via a controlled stimulation of the ovaries. An egg cell cannot be obtained from every follicle. During puncture not the follicle is retrieved from the body but a liquid is extracted from said follicle with the aid of a needle. If, for example, 16 follicles developed, approximately 12 egg cells can be obtained. Please note that this number is subject to individual fluctuation.

Relationship between extracted and mature egg cells:
Egg cells must achieve distinctive phases of development in order to be ready for extraction. While these phases are achieved by most egg cells, some will not succeed. For example: 10 out of 12 egg cells are mature, in other words they have reached metaphase II.

Relationship between mature and fertilized egg cells:
Although egg cells in a mature state fulfill all the requirements still not all of them can be fertilized the day after. This applies to both IVF and ICSI. It might be the case that only 8 out of 10 egg cells can be fertilized.

Relationship between fertilized egg cells and embryos with a regular development:
The further development of fertilized egg cells differs strongly. Not every embryo divides in a timely and regular manner. In such cases, it is possible that just 5 out of 8 embryos reach the blastocyst phase by day 5. All remaining embryos may show signs of an incomplete development insufficient for day 5.

Relationship between embryonic development and the possibility of cryopreservation:
After two embryos in their blastocyst phase have been transferred, three embryos in their blastocyst phase remain for cryopreservation. The last three left are not suited for this procedure.