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Patient guide

Doctor woman offering medical advices to a young couple in office

Introduction

The technology performed by Robert G. Edwards in the nineteen fifties has proven its efficiency for the first time in 1978, when the first child conceived with in vitro fertilization was born. By 1986 around 2000 children had been born with this technique, and by 2010 it was already 4.000.000 children. Over 15% of couples worldwide are dealing with infertility issues. In addition to other methods of assisted human reproduction and other methods to combat infertility, in vitro fertilization contributes to solving the problems for these couples.

What is in vitro fertilization?

All pregnancies start by a union of a female sexual cell (oocyte) and a male sexual cell (sperm). This process is called fertilization. From this union a unique cell is generated, containing genetic material from both parents, and by successive cell divisions an embryo, and subsequently a child appears. The fertilization process usually occurs in the fallopian tubes, where the oocyte travels after being released from the ovary following ovulation and the sperm travels after sexual contact. In the case of in vitro fertilization, this process occurs outside the female body, in a fertilization lab, and the resulting embryo is subsequently transferred to the mother’s uterus. In vitro fertilization therefore only changes the location where the fertilization and the first stages of embryo development occur, the rest of the pregnancy is normal. In the majority of cases, to obtain oocytes, it may be necessary to use medication stimulating the production and maturing of oocytes prior to harvesting.

Why IVF?

Not all couples dealing with infertility can benefit from in vitro fertilization. Main conditions with an indication and chances for success of in vitro fertilization are:

  • Disorders of the fallopian tubes (with tubal obstructions or disabling injuries)
  • Male sub-fertility (such as the reduction of the number or motility of sperm)
  • Endometriosis
  • Ovulation disorders (e.g. polycystic ovaries)
  • High levels of sperm DNA fragmentation
  • Infertility due to an unspecified / unknown cause

One variant of IVF is the technique by which a single sperm is injected into an egg-cell by IntraCytoplasmic Sperm Injection (ICSI). This method allows for fertilisation in cases when male infertility is severe.

What happens at the Column Medical Centre?

  1. The first discussion: The first step to obtaining a pregnancy via IVF is a detailed discussion between physician and couple – the so called infertility consultation. During this discussion the physician will examine your medical documents – analyses, previous consultations – so please bring any such documents along with you. Following this discussion, the physician decides if additional investigations are necessary or not. Once all the investigations requested by the physician were performed and collected, it is decided if in vitro fertilization is appropriate or not in your case. The minimum scale of investigations required in the IVF file for the Columna Medical Centre is attached as annex 1.
  2. Preparing your IVF file: In order to prepare your (printed/ hard copy) IVF file, a meeting with the person in charge of your case is necessary, during which your analysis results will be checked again and certain steps will be explained which you need to follow, to insure a smooth running of the entire process.
  3. Preparation for IVF: Call one of the phone numbers 021/3088080/ 0754999990 or contact your physician to make an appointment during the menstrual cycle previous to the one during which you plan on having the treatment. This consultation must take place no later than 14 days after the start of your menstrual flow. During this menstrual cycle you will need to use barrier contraception methods (condom, diaphragm, hood, etc.) in order to avoid getting pregnant.
  4. Preliminary consultation: During this consultation the new investigations performed and added to your file will be checked and possibly missing investigations will be completed, the physicians will explain the stages of the IVF process to you. On this occasion, the type of protocol is established for ovarian stimulation, according to the situation of your couple and the effective treatment starting date. Following the discussion with your physician, you will sign the informed consent forms and the one concerning financial obligations
  5. Ovarian stimulation: On the date set by your physician, you will start an injection treatment in one of the following variants, as recommended (recommendation made by your physician, according to the pathology underlying the couples infertility issue):
  • Long protocol
    • Single dose of an injectable analogue GnRH preparation, usually on the 21st day of the cycle previous to the one for which the IVF procedure is planned. Blood work and / or ultrasound 7-14 later shows if it is possible to proceed to step 2.
    • The daily injectable administration of a substance intended for ovarian stimulation, for 9 to 15 days, depending on your treatment response.
    • Ultrasound monitoring of the treatment response in this period: 2 to 3 ultrasounds may be required in this period, the first one usually 7 to 9 days after treatment.
    • The ovulation is triggered on the day established by the physician, with a hCG based substance, injected 35-36 hours prior to ovarian punction.
  • Short protocol
    • Daily administration, injectable, of a GnRH analogue, starting on the first or second day of the menstrual cycle after the consultation. A start-up ultrasound may be required, at the beginning of your cycle.
    • Adding a preparation for ovarian stimulation to be administered daily, via injection, depending on your treatment response.
    • Ultrasound monitoring of the treatment response in this period: 2 to 3 ultrasounds may be required in this period, the first one usually 7 to 9 days after treatment.
    • The ovulation is triggered on the day established by the physician, with a hCG based substance, injected 35-36 hours prior to ovarian punction.
  • Short protocol with Gn RH antagonists
    • The ovarian stimulation starts on the first days of your menstrual cycle
    • 5-7 days later another agent is added, inhibiting premature ovulation
    • The main complication of ovarian stimulation is the ovarian hyper-stimulation syndrome. This is an exaggerated reaction to the administration of medicine used in a correct dosage, for the induction of ovulation or ovarian stimulation. The main clinical manifestations of this syndrome include:
      • Abdominal pain
      • Volume increase of the abdomen
      • Nausea, vomiting
      • Diarrhoea
      • Shortness of breath
      • Fatigue, lethargy
      • Decreased urine output

 

Should you suffer from any of these symptoms during an ovarian stimulation process, please contact your physician or the Columna Medical Centre at 021/3088080 or contact the ambulance service. Notify any physician handling your case, the treatment you are following.

6. Harvesting oocytes and sperm: 35 to 36 hours after administration of the hCG oocytes and sperm are harvested. Oocyte harvesting is performed by ultrasound guided transvaginal punction, with or without anaesthesia. This intervention requires short term hospital admission and a previous appointment. Sperm harvesting can be made at the clinic (preferably) or at home, after a sexual abstinence time of 2-5 days (no more, no less), in a special recipient, on the same day as the oocyte harvesting. The harvesting method and location must be discussed with your physician prior to this day. Sexual activity is prohibited 3 days prior to the oocyte aspiration punction. The oocyte harvesting punction is performed under ultrasound guidance, in the punction room located next to the IVF laboratory, under general or analgesic anaesthesia, for which reason the patient must not eat anything, starting 8 hours before the appointed time. After the oocyte aspiration punction, the patient remains in the clinic for a few hours for monitoring, depending on her state. After the punction a pelvic discomfort and sometimes small vaginal bleeding may occur. If you experience any other symptoms you consider alarming, contact your physician or the Columna Medical Centre at 021/3088080 or 0754999990 or call the ambulance service.

After harvesting the oocytes and sperm – what happens in the embryology lab:

DAY 0 – Day of the punction for oocyte harvesting; fertilization is performed in the embryology lab, either via classic IVF technique or by ICSI technique. In case of the IVF procedure, oocytes and sperm are brought into contact in a special growth medium. For ICSI each egg-cell is injected with a single sperm, using a needle under special microscopic guidance.

Day 1: Some egg-cells are fertilized, however, others are not. The embryologist checks their evolution and you are informed.

Day 2: Fertilized oocytes are already divided into 2-6 cells, and depending on their number and aspect the decision is made to implant the embryos to the uterus on day 3 or to wait until day 5. You will be contacted on the phone and informed of the moment when this manoeuvre takes place.

Day 3: Fertilized oocytes with a good development may already have divided into 6-10 cells. On this day, the implantation of the embryos into the uterus can occur (embryo transfer), but in some cases we wait until day 5.

Day 4: The embryo is the morula stage.

Day 5: If embryo transfer did not occur on day 3, today is the day! The embryos have already reached the blastocyst stage.

7. Embryo transfer: Transfer of embryos to the uterus is a relatively simple and painless procedure which usually occurs 72 or 120 hours after the harvesting of oocytes, if valid embryos are generated during the laboratory fertilization. When transferring frozen embryos, the optimal time is established along with your physician. The technology consists of inserting a thin catheter which holds the embryos and the growing medium through the cervix and its complete evacuation inside the uterus. The couple decides on the number of embryos transferred to the womb. A large number of embryos increases the chances of the implant but also the risk for multiple pregnancy (twins, triplets, etc.) 2 embryos are transferred usually and the surplus can be conserved on request for several years. A subsequent transfer of frozen embryos no longer requires all the preliminary stages, but only a simple preparation of the uterus for implant.

Although recommended, the presence of the partner during embryo transfer is not mandatory.

8. Monitoring after embryo transfer. In two weeks’ time after embryo transfer, laboratory investigations may confirm or deny the success of the procedure.

9. Pregnancy monitoring: The pregnancy will be monitored by your gynaecologist just like any other pregnancy would be.

IMPORTANT ASPECTS TO KNOW ABOUT IVF:

  • The IVF success rate is usually 35-40% for women under 35, 25% for women aged between 35 and 37, 15-20% for ages between 38 and 40 and 6-10% for women aged older than 40. It is noteworthy that in case of a couple without fertility issues, with regular, unprotected sexual activity, the chances of obtaining a pregnancy are 15-17% in the first month, 70% in 6 months, and reach 95% in 2 years. The FIV Academy from within the Columna Medical Centre has a total success rate of 43.8% (for all age groups together).
  • Laboratory evolution is a process of natural selection: not all oocytes are fertilized, not all embryos evolve normally and the number of qualitative embryos, capable of implant decreases every day. This process continues even after the transfer of embryos to the uterus, including in the first 3 pregnancy months, when 20% of embryos stop evolving.
  • Freezing of embryos is only recommended for those which have developed at normal parameters. Part of / or all embryos may not survive the freezing/ unfreezing process even if they had a normal aspect prior to freezing.
  • In vitro fertilization is not applicable to every couple suffering from infertility – the opportunity to start this procedure is decided by the gynaecologist.
  • There is no difference between children born from natural conception and those borne from IVF, from the point of view of the percentage of malformations, intelligence, physical development. However in IVF multiples pregnancies are more frequent (around 25%). Foetal reduction in case of multiple pregnancies results in abortion, in 10% of cases.
  • The risk of foetal anomalies in case of IVF is similar with the one in pregnancies with normal conception (3-5%) and increases with age.
  • Using PGD (preimplantation genetic diagnostic), the specialists of the IVF Academy from the Columna Medical Centre makes sure that the risk of transmitting genetic disease is 0.
  • In order to decrease the rate of spontaneous miscarriages after an IVF procedure, the specialists of the IVF Academy from within the Columna Medical Centre use PGS (preimplantation genetic screening).
  • In case of repeated failures of the IVF procedures, there is a receptivity test (ERA) which may be performed on the patient to establish the optimal implant window. The ERA test is available at the Columna Medical Centre.
  • Lifestyle choices (drinking alcohol, smoking, faulty diet) and obesity are factors which may affect couple fertility, from the point of view of the male as well as the female.

Annex 1

Documents and analyses necessary in the IVF file

  • Copies of IDs for both partners
  • Blood group and RH for both partners
  • Serology for both partners: Ac HIV, VDRL, Ag HBs, Ac anti HBc, Ac HCV (valid for 6 months)
  • Psychological opinion on the couple, to enter the program
  • Wife:
    • Vaginal secretion: smear, cultures
    • Cervical secretion: smear, cultures (+/- Chlamydia Trachomatis antigen detection test), Mycoplasma/Ureaplasma cultures
    • Papanicolau Test (valid for 1 year)
    • TORCH: Toxoplasma (IgG, IgM), Cytomegalovirus (IgG, IgM), Rubella (IgG, IgM), HAV (IgG, IgM), Toxocara, Listeria
    • Hormonal dosing day 2-3 of the cycle: FSH, LH, Estradiol, Prolactin, Progesterone, AMH
    • TSH, fT4, ATPO, vitamin D, anti-thyroglobulin
    • Hospital discharge reports or results for histerosalpingography / hysteroscopy / laparoscopy
  • Husband:
    • Spermogramm
    • Halosperm test
    • Preop investigations (after finishing the stimulation treatment): Complete blood count, glucose, urea, creatinine, TGP, TGO, coagulogram (INR, APTT), fibrinogen, serum Na, serum K.
    • EKG + cardiology consultation
    • Preanesthetic consultation
  • Filled in and signed consent forms for both partners

Depending on your particular situation, your physician may ask for additional investigations or consultations from other specialities.

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