IVF/ICSI

In vitro Fertilization (IVF) and Intra Cytoplasmic Sperm Injection (ICSI)

Assisted reproductive technologies (ART) encompass all techniques involving direct manipulation of oocytes outside of the body. The first and still most common form of ART is in vitro fertilization (IVF), but other related techniques also reside within the realm of ART.

IVF involves a sequence of highly coordinated steps beginning with controlled ovarian hyperstimulation with exogenous gonadotropins, followed by retrieval of oocytes from the

ovaries under the guidance of transvaginal ultrasonography, fertilization in the laboratory, and transcervical transfer of embryos into the uterus.

ART has been greatly refined and expanded,

resulted in millions of births worldwide, and now accounts for 1–3% of all births in the U.S. and Europe. ART includes methods for assisted fertilization by intracytoplasmic sperm injection (ICSI) using sperm isolated from the ejaculate or obtained by microsurgical epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE), assisted embryo hatching, and preimplantation genetic diagnosis (PGD). In most cases, IVF is used to help an infertile couple conceive their own biological child, but donor sperm, donor oocytes, and gestational surrogates also play an important role in modern ART.

 

Other forms of ART include tubal transfer of oocytes and sperm (gamete intrafallopian transfer; GIFT), zygotes (zygote intrafallopian transfer; ZIFT), or embryos (tubal embryo transfer; TET) via laparoscopy.

What is in vitro fertilization?

IVF (In Vitro Fertilization) is the most successful ,commonly used and the last infertility treatment in whole world. The first baby was born in 1978 in England by this method and to date, more than 8 millions of baby was born following IVF treatment. If other treatments have failed, IVF is the method of choice for many clinicians and couples seeking for fertility. Herein, we summarized an IVF procedure:

 

  • Initial investigation for couples; basic hormones, sperm analysis and hysterosalpingogram.

Before IVF process, they evaluate whether the uterus and fallopian tubes are suitable for this procedure or not. These tests are performed to assess ovarian reserve and thyroid function. In addition, both male and female partners are tested for sexually transmitted infections and semen analysis is also performed for men.

 

  • Ovarian stimulation program for woman (short-long-soft protocols)

In order to grow available ovarian follicles, daily gonadotropin injections are used for about 10-14 days. Sometimes, pills may be used adjunct to daily shots. There are several ovarian stimulation protocols. Your healthcare professional will decide the best protocol for you. Here are common protocols for IVF/ICSI:

 

Long protocol:

Short protocol:

  • Oocyte retrieval procedure when optimal numbers of follicles reach a cut-off

When all mature follicles reach to at least 17mm, ovulation triggering is used to collect those oocytes. When the available numbers of follicles exceed 20, we frequently use specialized triggering agents to collect oocytes and freeze all the embryos. Oocyte pick up procedure is generally performed under mild anesthesia.

 

  • in vitro fertilization of oocytes with best selected sperms or microinjection of sperms into collected oocytes.

As soon as the oocytes arrive at the laboratory, the embryologists examine the maturity and quality of the oocytes. Two methods are used for fertilization of eggs. One of them is conventional insemination, the other is intra-cytoplasmic injection (ICSI). Both methods result in the same success rate. About conventional method, the sperm is placed into small petri dish then the sperm and eggs is fertilized together. About ICSI, sperm is injected into cytoplasm of the egg. The fertilization is checked the next day in both methods.

 

  • Putting fertilized ovums into an incubator for a while for further development.

Incubation of embryos is very critical. Very specialized units and incubation media are used for this process.

 

  • Selecting best embryos either using morphologic criteria or by preimplantation genetic biopsy

On day 3 or 5 of the incubation, embryologists check the growth pattern and other morphologic appearances of all embryos. If it is available, it is better to proceed with day 5 development. If there is an indication of preimplantation genetic testing, 5-6 cells are removed from day 5 blastocyst by using special biopsy equipment. All biopsy materials are send to genetic lab and embryos are frozen.

 

  • On 12th of embryo transfer, pregnancy test

This part is the most excited part of the treatment. Serum hCG is checked to document possible implantation of the embryo.

Reference: Speroff 8th ed.

 

 

 

Frequently Asked Questions and Answers on In Vitro Fertilization

  1. When is in vitro fertilization necessary?

As in vitro fertilization (IVF) was developed to treat women with blocked or absent fallopian tubes, it is preferred for the treatment of infertility related to endometriosis, male factor infertility and unexplained infertility. If the couple cannot have baby through natural methods, IVF treatment can be an option.

  1. Is there any risk related to having baby through in vitro fertilization?

Whereas some studies suggest that the incidence of birth defects is higher in children conceived via IVF treatment than in the general population (4-5% versus 3-4%), this increase may be due to factors other than IVF therapy. It is important to recognize that birth defects in the general population account for approximately 3% of births for major malformations and 6% for minor defects. Studies have revealed that academic success level and behavioral and psychological health of the children born through IVF treatment are parallel to those of the general population.

  1. Do the IVF drugs create risks for health in longer term?

As compared to the general population, infertile women have a slightly higher risk of ovarian cancer (approximately 1.6 fold higher rate). Considering that the majority of these infertile women also use fertility drugs, researchers argued that there may be a risk between the fertility drugs and ovarian cancer. Several studies have been conducted since 1992 when such a concern arose, but none of them could demonstrate an association between the fertility drugs or IVF and higher risk for ovarian cancer.

  1. Do IVF injections cause pain?

The likelihood of receiving a daily injection may be very high. Although injection is an essential part of IVF therapy, every patient should be carefully informed and supported about the drug administration to minimize their discomfort and stress. Medicines that needed to be injected into the muscle have been replaced by those which can be administered under the skin by a small injection (subcutaneously). Such injections are usually received over a period of 10-12 days, and then hCG, a hormone that triggers the ovulation at the end of the stimulation cycle, is given by the intramuscular injection. hCG injection, previously available only in intramuscular form, is now available in subcutaneous form (Ovidrel) for patients who wish to avoid intramuscular injection. Although the recombinant subcutaneous form of hCG in Ovidrel is not as long as intramuscular hCG, all markers are equally effective.

After the egg retrieval process, a progesterone supplement is given to the patient to prepare the uterine lining for embryo transfer. For most patients, progesterone can be taken in the form of a vaginal tablet or a vaginal suppository instead of injection. In this way, injection can be completely avoided in the second half of the IVF cycle. Vaginal tablets or vaginal suppositories of progesterone have been indicated to be as effective as progesterone injections.

  1. Is the oocyte retrieval (egg collection) procedure painful?

As anesthesia is applied during the oocyte retrieval, patients do not feel anything during the procedure. Oocyte retrieval is a minor surgery in which a small needle with an adhered interior ultrasound probe is placed into the vagina and slightly moved by means of the top wall. The needle is inserted into every follicle and it slightly extracts the oocyte through a slow suctioning function. On the completion of collection anesthesia rapidly decreases, and therefore, patients may feel small cramps in their ovaries which can be treated with appropriate medication.

  1. What is infertility that makes the application of IVF treatment necessary?

In general, infertility is defined as not being able to get pregnant after one year of unprotected sex. However, if you are 35 years old or older, you should have infertility evaluation after 6 months of unprotected sex so as not to delay the potentially necessary treatment.

  1. What are the common problems among women that may cause the need for IVF treatment?

Anovulation means lack of ovulation, or absent ovulation. Ovulation is the release of an egg from the ovary and must happen in order to achieve pregnancy. If ovulation is irregular, but not completely absent, this is called oligoovulation. Both anovulation and oligovulation are the results of ovulatory dysfunction. Ovulatory dysfunction is a common cause of female infertility, occurring in nearly 25% of infertile women.

  1. Is polycystic ovarian syndrome  (PCOS) is a valid ground for IVF treatment?

Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting 5-10% of women. It is one of the most common reasons of female infertility in IVF treatment.

 

  1. Is obesity a cause of infertility in IVF treatment?

When obesity is considered, its association with hypertension, diabetes mellitus and cardiac diseases is the first thing that comes to mind. However, many people get surprised when they find out the relation between obesity and infertility. Epidemiological data confirm that obesity accounts for 6% of primary infertility, and even more surprising, that low body weight in women accounts for 6% of primary infertility. Thus, 12% of primary infertility results from deviations in body weight from established norms, and that this infertility can be corrected by restoring body weight to within normal established limits. More than 70% of women who are infertile as the result of body weight disorders will conceive spontaneously if their weight disorder is corrected through a weight-gaining or weight-reduction diet as appropriate.

  1. I have endometriosis (chocolate cyst), should I apply for in vitro fertilization?

Endometriosis, also known as the chocolate cyst, is an often painful disorder in which tissue that normally lines the inside of your uterus (endometrium) grows outside your uterus. Endometriosis most commonly involves your ovaries, your bowels and the tissue lining your pelvis. Rarely, endometrial tissue may spread beyond pelvic organs potentially resulting in infertility. A great majority of the women applying to IVF treatment have endometriosis.

  1. I have myoma, do they affect IVF outcomes?

Uterine myomas are frequently seen after delivery. Uterine myomas, also known as fibromyomas, leiomyomas or myomas, are not associated with increased risk for uterine cancer and almost never turn into carcinomas. Fibroids that change the shape of the uterine cavity (submucous) or are within the cavity (intracavitary) decrease fertility by nearly 70% and the removal of such fibroids increases fertility by 70%. Other types of fibroids, those that are within the wall (intramural) but do not change the shape of the cavity, or those that bulge outside the wall (subserosal) do not decrease fertility, and thus, the removal of these types of fibroids does not increase fertility.

  1. Does IVF treatment affect ovarian reserve?

There is no evidence demonstrating that normal laparoscopic or ultrasonographic oocyte retrieval damages the ovary. Indeed, some reports in the literature suggest that the couples with a history of infertility achieved pregnancy after an ovarian biopsy.

  1. Will there be an oocyte in each follicle collected in IVF?

It varies from patient to patient. In some patients, oocyte may not be found in up to 50% of the follicles.

  1. Is there a risk of multiple pregnancies in IVF treatment?

Yes, if more than one embryo is transferred. Twin births account for 25% of pregnancies achieved by IVF (In normal population, twin births occur naturally in 1 out of every 80 births). Triplets create 2-3% of IVF pregnancies. Nevertheless, necessary precautions have been taken in IVF treatment and in Turkey to prevent from the risk of multiple pregnancies.

  1. Is there a risk of abnormality in children conceived via IVF?

The risk of abnormality in IVF is as much as the risk in normal pregnancies.

  1. How long does IVF treatment take?

Whereas the time required for each patient varies, the procedure is generally completed within three to six weeks. Fertility medicines are used to stimulate the ovaries. Afterwards, patients are followed up with ultrasonography exams and through hormone levels four to ten days before ovulation.

  1. What happens to unused embryos?

Patients are offered several options regarding the disposal of the residual embryos including the option of freezing embryos for later use.

  1. Is there a risk of miscarriage in IVF?

The rate of miscarriage is nearly equal in general populations and in those undergoing IVF. For older women, the rate of miscarriage is normally higher. As the pregnancy test is performed two weeks after the transfer of embryos, spontaneous miscarriage may occur at every early phase of pregnancy.

  1. Does IVF decrease my ovarian reserves?

A woman is born with a full complement of eggs. There are far more eggs than will ever be used during a normal lifetime and IVF procedures do not have any measurable “lowering” effect.

  1. What can be done to improve sperm quality in IVF treatment?

The quality of sperm is associated with what happened in men’s body 3 months before the day of ovulation because sperm maturation takes 3 months. The following are the guidelines to ensure the semen sample comes out in the best quality possible.

Fever experienced 3 months prior to IVF treatment may adversely affect the sperm quality. While the count and motility seem normal, fertilization may not be achieved. The use of alcohol and smoking should be minimized during IVF. Avoid using all kinds of supplements containing testosterone, DHEA and Androstenedione / Androstanediol hormone.

  1. Does weight loss affect my chances of getting pregnant?

Yes. A Body Mass Index (BMI) of over 30 kg/m2 is defined as obese and a BMI of 25-30 kg/m2 is defined as overweight. (Calculate your body mass index here.) Obesity is associated with many medical problems including infertility. In obese and overweight women, infertility is primarily related to ovulatory dysfunction.

  1. What is folic acid used in IVF treatment and why is it applied as an adjuvant therapy?

Folic Acid, also known as Vitamin B9, is a part of the B-Vitamin family. Our body needs folic acid to be able to produce healthy red blood cells, noradrenalin and serotonin (chemical substances in the nerve system). Folic acid helps the synthesis of DNA (genetic material) and is one of the main components of the cerebrospinal fluid. During the preconception period, adequate folic acid intake before and after the pregnancy helps women protect against various birth defects, including neural tube defects such as spina bifida (the most important birth malformations resulting from folate deficiency). Additionally, it reduces the risk of congenital heart defects, cleft lip, extremity exfoliation and urinary system anomalies by 40%.

Every woman that desire to get pregnant should take folic acid supplements daily and have a diet rich in folate to decrease the risk of a baby with disorders. Folic acid intake must be continued till the end of the first trimester.

  1. Does the use of fertility drugs cause cancer?

A large epidemiological study was published in Denmark in 2009. This study stated there was no convincing relationship between the use of fertility drugs and the risk of ovarian cancer. Also, no association was identified between fertility drugs and the number of cycles used, duration of follow-up or parity.

  1. Is IVF treatment applied only in case of female infertility?

It was reported that 40% of infertility cases were related to men, 40% related to women and 20% of the cases related to “unknown reasons”.

  1. Does bleeding occur after oocyte retrieval?

Spotting is a common side effect seen after oocyte retrieval. It may be a slight spotting  that will disappear spontaneously within a short time.

  1. Is embryo transfer a painful procedure?

Embryo transfer causes no pain.

  1. Is bed rest recommended after embryo transfer?

After the transfer, patients should have rest at the rest of the day; however, they can return to their daily routine on the following day. In case of increased risk of hyperstimulation, it is recommended to decrease activity for a few days till hyperstimulation is eliminated.

  1. When does pregnancy start after IVF treatment?

Women should wait 12 days after IVF to identify a potential pregnancy. If pregnancy is achieved, it can be understood with a blood pregnancy test to be obtained 12 days after embryo transfer.

  1. Does a man need go to the medical center often during IVF?

It would be enough if the father-to-be comes to the center in the first phase when infertility problems are diagnosed and in a later phase to give semen samples.

  1. Is IVF treatment a costly procedure?

The cost of IVF treatment depends on the needs of each patient. There are several reasons underlying the fact that the cost of IVF varies from patient to patient as well as from center to center. Several factors including infertility related reasons, success rate of the medical center, the age of the potential mother, drugs to be used and the preferred IVF method cause variation in prices.