In Vitro Fertilisation (IVF)

IVF became known in 1978 with the birth in the United Kingdom of Louise Brown. In Spain, they began using the procedure in 1984 and at CEFIVA we started the first in-vitro fertilisations in 1989.

Indications for IVF

The introduction of more advanced Assisted Reproduction Techniques means that IVF is being used less and less. Nowadays, the indications for IVF are:

Tubal factor: obstruction of the fallopian tubes.
Failure of AIH.
Endometriosis.
Ovary failure.
Sterility of unknown origin (SUO).
Moderate male factor.

Once the pre-IVF screening has been carried out, to check that the conditions are such that the process has a reasonable chance of success, the couple is included on the definitive list. At this point they have to give their signed informed consent authorising the procedure.

They will be provided in writing with prescriptions for the necessary medications, the treatment regime, where they should go to have the analyses, ultrasounds, etc. They will also be told when to contact us to commence the treatment.

Remember that many of the medications are administered subcutaneously, which is a very simple and painless form of administration and means that the majority of patients learn how to give their own injections, thereby avoiding being dependent on other people.

Ovary stimulation

Consists of a hormone treatment (Gonadotrophins) which is injected daily in order to stimulate the growth of follicles inside the ovaries. This makes it possible to collect several eggs, something which would not happen in one cycle without stimulation, later allowing a selection to be made from the embryos which are to be transferred to the uterus and so increasing the technique's chances of success.

Not all ovaries respond in the same way to the stimulation, not even the ovaries of the same patient in different cycles. Therefore, the medication and the treatment regime will vary according to the patient, the most appropriate being administered in each case. The start of the treatment will be confirmed by the Gynaecologist.

During this stage strict monitoring is required of the oestradiol levels by way of blood analysis, and of the number and the growth of follicles in the ovary, visualised by a series of ultrasound scans.

According to the response of the ovary, the hormone treatment is adjusted until the suitable maturity is reached and the optimum moment is determined for extraction of the eggs. This phase lasts approximately 12-14 days.

Monitoring

The ovules develop inside small "cysts" called ovarian follicles. These follicles produce a hormone called Oestradiol, which increases according to the growth of the follicles. This process has to be monitored through blood analysis and ultrasound scanning.

- Blood analysis

You will be given a time at which a blood sample will be extracted, starting on the day the gynaecologist considers appropriate for measuring the oestradiol. It is important to arrive on time for your blood test as the laboratory cannot begin the analysis technique until the blood samples from all the patients allocated to that day have been processed. It is not necessary to fast for this type of analysis, but it is advisable to avoid eating large amounts of food. The result will be available within 2 or 3 hours.

 

 

- Ultrasound. This technique will tell us the number and size of the follicles. The patient will be instructed as to the day on which the ultrasound monitoring will commence.

 

The information obtained on Oestradiol and from the ultrasound scans allows us to know the number and degree of maturity of the follicles and therefore assess the response to the treatment, make any necessary dose adjustments in each case, and predict the day for the egg retrieval at least 48 hours in advance.

Each woman responds differently to the medication. There is therefore no need to worry if either your Oestradiol figures or the type of treatment you are receiving are not the same as another patient's. You should be aware that there are many and varied drugs available for stimulating ovarian function.

- Administration of H.C.G

This is a hormone which induces ovulation. It will be administered the day before the retrieval. You will be given a time at which one of the following drugs will be administered:

-Ovitrelle: one ampoule subcutaneously, or:

-HCG Lepori 2500 IU 4 ampoules IM.(TOTAL 10,000 IU) or 10,000 I.U. of H.C.G. (Profasi) intramuscular, at a specified time which you should not change without giving prior notice (usually between 8 and 10 o'clock in the morning). It is important to remember that, unlike the previous injections, this injection must be intramuscular.

 

Follicular Puncture (Egg Retrieval)

You will be given a time to attend the clinic.

The retrieval will be carried out with local anaesthetic and sedation. The technique is painless and does not require admission, the patient being able to go home after an hour's rest.

The egg retrieval is done via the vagina with ultrasound monitoring, the follicular liquid being aspirated into the inside of a tube, which is taken immediately to the Laboratory.

You will be given a time when you should contact the Laboratory to find out how the first phases of fertilisation are progressing and inform of any post-retrieval incidents.

Obtaining the semen on the day of the retrieval

The samples will be obtained at a specified time, by way of masturbation into a sterile recipient, following the instructions which you will be given beforehand. The sample must normally be handed in an hour before the retrieval.

For some patients, it can be difficult to obtain a sample under these condition, for which reason, prior to the beginning of the I.V.F. cycle, one or more samples of semen will be frozen.

In some cases, always for medical reasons, semen from the bank will be used, following acceptance and written authorisation from the couple before initiating the I.V.F. cycle.

The patient normally obtains the semen sample at home and, maintaining it at the appropriate temperature, hands it in to the laboratory when he comes to the Centre with his partner for the egg retrieval. Abstinence from sex is recommended for 2-7 days and the sample should be handed in no more than one hour after it has been produced.

I.V.F. Laboratory

Once the follicles have been emptied, the aspirated follicular fluid is taken to the laboratory for identification of the eggs. Eggs are not obtained from every follicle. After they are identified, a morphological classification is done according to their degree of maturity, and they are placed in culture medium.

Once in the laboratory, the sample is washed and after cultivating for 1 hour in a CO2 incubator at 37ºC , the sperm are inseminated into the dishes or microdrops containing the eggs.

At 18 hours post-insemination (day + 1) the first observation is made to check whether fertilization has occurred (presence of 2 pronuclei)

A second observation is made the following day (day +2), the next step being classification of the embryos and then transfer of embryos, at the time considered to be most opportune.

It can also be usual to perform the transfer on day + 3 and even on day + 5, according to Clinical judgement or that of the Laboratory.

In the event that there are surplus embryos, due to not having been transferred to the uterus, these will be frozen. If you do not agree with the freezing of embryos you should make this known before the egg retrieval is carried out. You should be aware of the possibility of: 1.- Donating the eggs which are not going to be used to patients who do not have ovules and whose only chance of attempting to become pregnant is through donation of eggs by another woman. 2.- Destroying those not used for fertilisation.

Under these circumstances, no more than three eggs can be exposed to fertilisation.

For the moment, the freezing of eggs is an experimental process and the majority of human ovules are damaged by the freezing process (unlike what happens with sperm or already fertilised ovules (embryos)).

Transfer of embryos

The next step in this phase is to place the embryos inside the uterus using a catheter. This is a painless procedure which does not require any special preparation. It is normally carried out approximately 48 to 72 hours after the retrieval.

This is a simple technique and does not require any type of medication or anaesthetic. The patient should come with a full bladder, which facilitates both the view on ultrasound and the transfer itself. The embryos are loaded into a catheter which is passed through the neck of the uterus to the uterine cavity, where they are then deposited. In some specific cases the transfer may be made into the inside of the fallopian tube.

See video

The number of embryos to be transferred depends on various factors: age of the patient, cause of the sterility, previous attempts with IVF, embryo quality, etc.

It will be checked that the embryos have not remained adhered to the catheter. The patient will then go about her usual routine, with advice to take things quietly, avoid sexual relations until the IVF result is known and be prescribed treatment with gestagens, generally Progesterone pessaries.

At 15 days after the embryo transfer, if the patient has not menstruated, a blood analysis (ßHCG) is advised to test for pregnancy. Even once the pregnancy test has given a positive result, it must be remembered that it is still very early to know whether the pregnancy will follow its normal course. The gynaecologist will arrange a date for an ultrasound scan which will allow confirmation of the pregnancy by viewing of the gestational sac and the heart beat.

It is important, both in cases of success and failure, to remain in contact with your gynaecologist.

As in natural conception, in IVF early miscarriages or ectopic pregnancies can occur, which must be appropriately diagnosed and treated.

The risk of foetal malformations or chromosome abnormalities following IVF is the same as for spontaneous pregnancies.

With IVF, multiple pregnancies are more common than with natural conception, due to the fact that normally more than one embryo is transferred in order to increase the possibilities of success.

The objective of the CEFIVA Team is to offer the couple a single pregnancy and avoid multiple pregnancies. To do this, we are making advances in knowledge about the optimum number of embryos to transfer according to different factors: Indication for the technique, the age of the woman, previous attempts, embryo quality, etc

Embryo freezing programme

If after carrying out the In Vitro Fertilisation cycle, there are surplus embryos, due to their not having been transferred to the uterus, these will be frozen. When giving their informed consent, the couple will be made aware of the obligations that this process involves.

Legal aspects of the freezing of embryos

Royal Decree 1720/2004 of 23rd July

Art.2 Undertaking by the couple

In those cases (referring to the surplus embryos), in which the extra pre-embryos generated will be cryopreserved for a period of time equivalent to the fertile life of the woman, with the purpose that they may be transferred to her at later attempts, the parents shall have to sign an "obligation of responsibility over their cryopreserved pre-embryos", conforming with and under the terms and limits of informed consent established in article 11.3 of the cited Law 35/1988 of 22nd November, as laid out in Law 45/2003 of 21st November.

Article 11.3 of Law 35/1988 of 22nd November, as laid out in Law 45/2003 of 21st November.

11.3.- When, in the exceptional cases foreseen in section 3 of article 4, extra embryos have been generated, these will be cryopreserved for a period of time equivalent to the fertile life of the woman, with the purpose that they may be transferred to her at later attempts. The parents shall have to sign an "obligation of responsibility over their cryopreserved pre-embryos". This shall include a clause by which the couple, or where applicable, the woman, shall give their consent in order that, in the event of the cryopreserved pre-embryos not being transferred to her within the specified time, they would be donated for reproductive purposes as sole alternative.

Possible failures

1 - Before the egg retrieval

The cycle may be stopped at any time if the possibilities of obtaining good quality eggs are reduced.

The most frequent causes which may force cancellation of a cycle are:

- There are not sufficient follicles.
- Abnormal oestradiol levels, which tell us that the ovules we were going to obtain would not be of good quality.
- Ovulation occurs before the time for egg retrieval.

2 - No eggs are obtained

On very rare occasions, no eggs are obtained from the egg retrieval, possibly due to access to the follicles being difficult, that ovulation has occurred unexpectedly or due to inadequate administration of HCG. Maximum attention must be given to instructions in this respect: time and method of administration.

3 - No eggs are fertilised.

Failure of fertilisation in IVF is not common, but there are occasions when, due to unknown causes (good sperm and egg quality) the eggs do not fertilise. Should this occur, and before attempting a new treatment cycle, further studies would have to carried out. DGP The performing of PGD may be indicated, which at times allows us to establish the reason for the fertilisation failure.

4 - No embryos become implanted.

Once the embryos are transferred inside the uterus, only in 25-40% of cases do they become implanted, leading to a pregnancy.

In the majority of occasions, it will not be possible to explain why pregnancy has not occurred, since in nature it is normal that only 30% of the embryos which arrive in the uterus become implanted.

5 - Seminograma, Test de mejora espermática y congelación de la muestra seminal.

Aunque el varón haya efectuado seminogramas con anterioridad es preciso analizar nuevamente el semen con el fin de valorar la técnica de reproducción más adecuada según su calidad.
También se congela la muestra seminal (en caso de FIV_ICSI) quedando reservada como medida de seguridad, hasta el día de la punción folicular en que se solicitará una nueva muestra de semen fresco que se utilizará para la realización de la técnica a aplicar. La muestra congelada se destruirá una vez que pudo ser utilizada la muestra en fresco, a no ser que el paciente manifieste su deseo de mantenerla en el Banco de semen, para lo cual deberá de ponerse en contacto con el Laboratorio.

5 - Semen Analysis, Test of sperm quality and freezing of the semen sample.

Although the male may have had previous semen analysis, it is necessary to analyse the semen once again with a view to assessing which reproductive technique is most appropriate according to its quality. In addition, the semen sample is frozen (in the case of IVF_ICSI), being kept as a safety measure until the day of the follicular puncture, when a new sample of fresh semen will be requested, to be used for the technique being applied. The frozen sample will be destroyed once it has been determined that the fresh sample can be used, unless the patient has expressed a wish for it to be stored in the Sperm Bank, in which case he will have to contact the Laboratory.

6 - Specialised tests

In certain cases it is necessary to request specialised tests or reports from specialists from other areas before attempting the fertilisation process.

Genetic studies:

- Karyotype
- Microdeletions of the Y chromosome
- Cystic Fibrosis gene mutation screen
- FISH of sperm
- Study of meiosis in sperm
- Informativity studies

PCR studies of washed semen in HIV,HCV... seropositive patients