IVF/ICSI in Dr. Shterev Hospital – what to expect - accents

- The IVF/ICSI procedure last approximately 15 days – from the first stimulation day till the embryo transfer.

- Ten days after the embryo transfer the patient should do a blood pregnancy test, that shows beta-human chorionic gonadotropin (hCG). On the 12th day, the patient does a urinal pregnancy test at home. If the test is positive, 20 days after the transfer the patient should do the first ultrasound test.

- "In the last years with my colleagues in Dr. Sherev Hospital have helped 6000 families to hear the "Annunciation" – the news that they will have a baby", Prof. Tanya Timeva, Head of IVF department.

IVF/ICSI – what to expect

Step 1 | Drafting a stimulation protocol for IVF/ICSI
Before the start of the In Vitro/ICSI procedure, the doctor specifies the protocol for stimulation. There are several types of those protocols:
• Spontaneous (natural) cycle – the goal is to aspire one mature oocyte with good quality

• Limited cycle (minimal stimulation) – the goal is to aspire not less than four mature, oocytes with good quality

• Controlled ovarian hyperstimulation (COH) – the goal is to aspire between 4 and 15 mature oocytes with good quality:
о Long protocol – starts with suppression of ovarian function in the 21st day of the previous menstrual cycle. The COH lasts 20-25 days.
о Short protocol (so-called antagonist protocol) - stimulation starts in the second day of the menstrual cycle. COH lasts 10-12 days.

The first day of the menstrual cycle is considered the day with evident regular bleeding. If there is spotting in one day, the first day of the menstrual cycle is supposed to be the next one.

Step 2 | |Tests regarding Regulation 28 for Assisted Reproduction
Female patient: HIV, Syphilis, Hepatitis B, Hepatitis C, microbiology of the vaginal discharge, cervical smear (PAP test)
Male patient: HIV, Syphilis, Hepatitis B, Hepatitis C, microbiology of semen

Step 3 | Signing informed consents for proceeding IVF/ICSI

Step 4 | Controlled ovarian hyperstimulation (COH)

The goal of the controlled ovarian hyperstimulation (COH) is to aspire several mature oocytes. It gives an opportunity for more embryos to be produced during the following laboratory fertilization and increases the chances for pregnancy. There is a particular scheme for the stimulation with medication, like are Elonva, Gonal F Pen, Puregon Pen, Merional, Fostimon, Menogon, etc.

With a few ultrasound tests and Estradiol blood levels tests, our embryologists monitor how the oocytes react to the stimulations. During the ultrasound tests, the number and size of the follicles are observed, as well as the thickness of the uterine lining. To prevent ovulation, the blood level of LH is being tracked, and medications are used to suppress it (as like Cetrotide, Orgalutran). The controlled ovarian hyperstimulation continues till:
o the dominant follicles reach diameter more than 18 mm;
o the thickness of the endometrium reaches not less than 8 mm;
o Estradiol levels correspond with the amount of the growing follicles (more than 250 pg/ml/follicle).

With the presence of the described conditions, the patient will be injected with human chorionic gonadotropin (hCG) for starting the process of maturing the oocytes. This is when te use of the medicaments for ovarian hyperstimulation stops. Usually, the hCG injection is done 36 hours before the puncture of the follicles.
Few days before the before the puncture of the follicles the patient should pass some lab tests. The results are valid for seven days. The tests include Erythrocyte Sedimentation Rate (ESR), Full blood counts (FBC), Glucose, ALT, AST, prothrombin time (PT), Fibrinogen, aPTT, etc.

Additionally, a consultation with an anesthesiologist and cardiologist is mandatory before every puncture. During these consultations, the patient fills a questionnaire about previous surgical interventions, drug allergies, blood transfusions, chronic diseases, etc. Blood pressure and ECG are measured, and the results are reviewed.

Step 5 | Follicle puncture
Puncture preparation
To allow a follicular puncture to be scheduled, ovulation is induced artificially by administering hCG about 36 hours before the planned puncture. The patient should stop taking food and liquids after 22:00 the previous evening. She has to come in the hospital 45 minutes before the puncture. The following procedures will be made before the puncture:
Enema – it is a mandatory procedure before a puncture. The goal is cleaning the intestinal contents of the extremities of the large intestine located in the small pelvis - very often the full intestine impedes access to the ovaries.
Toilet – removing the body hair of the intimate parts. It is mandatory because of the risk of infections during puncture. You can also do this at home.
Peripheral venous catheter – this is plastic, sterile, onetime cannula intended for gripping an outer venous vessel. The goal is to be prepared in case of a need for additional measures – implementing medicines, blood transfusion, etc.

Follicle puncture
Collection of oocytes is made through the vagina under ultrasound control and short-term general anesthesia. The access to the ovarian is through an aspiration needle, placed on the ultrasound tip. The follicular fluid is aspirated with the needle and given to the IVF laboratory, where the embryologists determine the number of the oocytes. The procedure lasts until the check of the follicular fluid of both ovaries. The number of follicles is not the same as the number of oocytes. The transvaginal follicle puncture is a relatively safe procedure. There is no pain during the process. Usually, it takes about 15-20 minutes and the time depends on the number of follicles.

After the procedure
It is mandatory to stay under intensive medical observation in the hospital for about 4 hours and be tested the blood pressure and pulse. Two hours after the procedure the patient may start taking some food and water. The patient will begin moving a bit, and there will be an ultrasound test. The presence of light bleeding, pelvic pain and abdominal pain, nausea are possible. In the case of most laborious pains, you should call your doctor. It is recommended not to drive in the first 24 hours after the procedure.

In the days between the puncture and the embryo transfer, you must keep in touch with your doctor and embryologist to get needed information about the embryo development and to set the day for the embryo transfer.

Step 6 | Provide semen from the partner
The partner provides sperm on the day of the puncture. The partner's sexual abstinence for 3-5 days before collecting the sample is mandatory. Alcohol in large quantities is not recommended during this period (for example, a glass of beer or wine is acceptable). Sexual abstinence for more than 7-10 days may damage the semen. The semen should be collected by masturbation, taking the appropriate hygiene measures in a special and very cozy room with all needed facilities.

The semen specimen should be collected in a wide-mouth sterile container which will be provided beforehand or which may be bought at a chemist (like those used for urine collection), and it should be labeled with name, days of abstinence and time of collecting. It is recommended that before the masturbation, the man wash his hands and genitals with soap and warm water and dry with a clean cloth. It is crucial that the entire ejaculate is collected without losing any. The semen specimen should be collected in a wide-mouth sterile container which will be provided beforehand.

In case the partner is not able to provide semen on the day of puncture, it is possible to do it before that day. In this case, the semen is frozen and subsequently thawed on the puncture day. Once in the laboratory, the specimen is processed to select the most mobile sperm and get enough concentration of quality sperm for the fertilizing procedure.

When donor's sperm is used for in vitro/ICSI procedure, the patient should be informed in advance with the available donors in the sperm bank. Dr. Shterev Hospital uses Cryos International – a Danish specified sperm bank, which is approved by the Bulgarian Executive Agency for Transplantation and all the donor donation, transportation and storage fully comply with Bulgarian legislation Regulation No 28 for Medically Assisted Reproduction, 20th of June, 2007. All donors are screened for transmissive deceases and had passed through genetic screening. Regarding Bulgarian regulations, donors stay anonymous.

The patient receives in advance a catalog with potential donors with information about the race, nationality, eye color, hair type, height and weight, job and blood type included.
Some of the donors have extended profiles with child pictures of the donors and additional information about his genealogy. Sometimes the donors write an essay about: "Why I became a donor" where his handwriting may be seen. Usually, the patient chooses and arrange top three wished options. The reason is that because of the significant amount of procedures in the hospital, the first donor material may be sold out.

Step 7 | Fertilization
The fertilized embryos are being grown for 3-5 days in the laboratory. For embryos comfort, they are put into conditions that are maximally close to those in the women uterine. It  happens with the help of:

o An incubator that held the body temperature, certain levels of humidity and CO2 concentration.
o An environment for cultivation with a composition that is maximally close to the context of the uterus and the fallopian tubes.

What happens to the embryos in the incubators?
Day 0 (the puncture): the oocytes that are aspired during the follicles puncture are examined under a microscope and classified due to their quality and maturity. Next, they are put in a special medium for cultivation. A few hours later, depending on their maturity, 50-200 000 sperm cells are added to each of them (classical fertilization). All of them are put in a labeled petri dish in the incubator.

Very often ICSI is used when there are poor semen results – low or missing motility, low sperm count, high levels of abnormal sperm morphology. The procedure is close to the IVF procedure, and the difference is that one spermatozoon is chosen by micromanipulation system. It is injected in the oocyte cytoplasm. This procedure provides opportunities for fertilization in cases with a low concentration of sperm cells, reduced sperm motility and after microsurgical sperms retrieval (PESA/TESE).

Day 1: on the next day the oocytes are tested for fertilization. The symptoms of fertilization are in the appearance of two pronucleus – 2PN (one appeared from the spermatozoon and one – from the oocyte);

Day 2: fertilized oocytes undergo a series of cleavage divisions, progressing through 2-cell, 4-cell, called blastocysts;

Day 3: if the development is in norms, there are about eight blastocysts;

Day 4: the embryo development continues;

Day 5: starts the process of change in shape of the embryo that is called compaction.

Step 8 | Luteal support
After the follicular puncture, your doctor will prescribe you the use of progesterone preparation in the form of vaginal capsules to increase the success rate of implantation. Those vaginal capsules should be put three times a day until the pregnancy test. In case of a positive pregnancy test, the use of progesterone capsules continues till the 12th gestational week.

Step 9 | Embryo transfer
Embryo transfer involves transferring one or more embryos that are at a very advanced stage of development into the uterus. Usually, embryo transfer can be done on day three or day five after the follicular puncture. It is possible to be done on day four too. You need to come in the hospital 45 minutes before the manipulation when the embryo transfer is scheduled. Before the procedure, you will be injected with medication with smoothing and muscular relaxing effects. Usually, 1 to 3 embryos are transferred. The goal is to increase the chances for pregnancy but also to decrease the chances for multiple pregnancies.

The decision for the embryo transfer procedure day is taken individually for every patient. It depends on the development of the embryos, their quantity, patient's age and how many in vitro procedures the women had gone through. It is a significant decision that the doctor takes along with you and the embryologist.

The embryo transfer procedure is painless and takes just a few minutes. The embryo transfer procedure starts by placing a speculum in the vagina to visualize the cervix, which is cleansed with saline solution or culture media. A soft transfer catheter is loaded with the embryos and handed to the clinician after confirmation of the patient's identity. The catheter is inserted through the cervical canal and advanced into the uterine cavity. It feels like a vaginal smear test procedure, and there is no need for anesthesia.
It is advisable to stay in the hospital for an hour and rest for the rest of the day after the embryo transfer.

The good quality embryos that have not been transferred (if any) may be frozen and used for another procedure – so-called Frozen Embryo Transfer (FRET).

You do not have to lie all the time after embryo transfer. It is advisable to avoid heavy physical exercises like running, gymnastics and swimming, and as well as not lifting heavy things. Read more about what is not advisable to do after embryo transfer in our After Embryo Transfer" leaflet.

Step 10 | Pregnancy test
A blood test for pregnancy is taken ten days after the embryo transfer. It reports the so-called beta hCG. On the 12th day, the patient should do a urine home pregnancy test. If the test is positive, the first ultrasound test is scheduled in 20 days after the embryo transfer.


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Video: How the IVF/ICSI works

Watch our cartoon video, in which brightly and funnily we introduce the stages of an IVF/ICSI procedure.

ICSI - resume