Ovarian Stimulation

 Egg and Sperm Collection

 IVF and Microinjection (ICSI)

 Embryo Transfer

 Assisted Hatching

 Cryopreservation

 Success Rates

In the IVF procedure, collected sperm and eggs are brought together and are fertilized outside the body (in vitro).

Tests done before IVF 

After having decided to undergo IVF treatment, couples are tested for Hepatitis B and C, HIV (AIDS), and VDRL. Women are checked for factors that might affect pregnancy. Levels of the reproductive hormones (FSH, LH, Prolactin, Estradiol) in the blood are checked for on the 3rd day of the period. Important for visualizing the uterus and for acquiring other information, a hysterosalpingogram (HSG) taken at most 6 months earlier is also required. In this procedure a dye is injected through the cervix and an x-ray is taken to determine whether the fallopian tubes are open and whether the shape of the uterine cavity is adequate for pregnancy. A light anesthetic may be given during this procedure. 

Another procedure that may be used to evaluate the uterus before IVF is a hysteroscopy. In this procedure a small fibre optic telescope is inserted through the cervix into the uterus, the uterine cavity is evaluated and if required, surgically repaired under general anesthesia. 

Again, another procedure that may be used is a laparoscopy where a telescope is inserted through or below the navel to view the reproductive organs. This is also done under general anesthesia. Pelvic adhesions, ovarian cysts, small fibroids and endometriosiscan be surgically removed by inserting other small instruments through other incisions.

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Ovarian Stimulation

The treatment undertaken depends on the woman's age, her hormone levels and her weight/height ratio. In the most commonly used IVF protocol, the ovaries are stimulated after hormone suppression is achieved:

Ovarian Stimulation: During ovarian stimulation, also known as ovulation induction, ovulation drugs, or “fertility drugs,” are used to stimulate the ovaries to produce multiple eggs rather than the single egg that normally develops each month. Multiple eggs are needed because some eggs will not fertilize or develop normally after egg retrieval. Pregnancy rates are higher when more than one egg is fertilized and transferred to the uterus during an IVF treatment cycle. 

Ovarian stimulation is achieved with daily FSH or FSH-LH injections. The ovaries are evaluated during treatment with vaginal ultrasound examinations to monitor the development of ovarian follicles. As follicles develop, monitoring is done at shorter intervals and blood samples may be drawn to measure response to ovulation drugs. Hormonal doses can be adjusted if stimulation is thought to be progressing slowly. Using ultrasound examinations and blood testing, the physician can determine when the follicles are appropriate for egg retrieval. Generally, 1-3 weeks of FSH  injections are required for adequate follicular development. In 10 % of cases, the stimulation may be cancelled due to inadequate ovarian response. 

Folicular Puncture: When the follicles reach the appropriate size and number and the emdometrium the proper thickness, hCG or other medications are injected. The hCG replaces the woman’s natural LH surge and helps the eggs to mature so they may be capable of being fertilized. The eggs are retrieved before ovulation occurs, usually 34 to 35 hours after the hCG injection. Because of this, the hCG injection is administered after 8PM.

Occasionally, a cycle may be cancelled to reduce the risk of severe ovarian hyperstimulation syndrome (OHSS). It is important to call the doctor when symptoms of this syndrome (abdominal bloating, vomiting and pain) appear. The ovaries become larger than normal and fluid can accumulate in the abdomen or rib cage causing pain. Severe OHSS cases may require hospitalization. This syndrome is seen most often in women with polycystic ovarian syndrome.  The syndrome can be avoided by close monitoring of the patient and appropriate drug choice.

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Egg and Sperm Collection

Egg retrieval is usually accomplished by transvaginal ultrasound aspiration, a minor surgical procedure that is performed at the center. Some form of anesthesia is generally administered during this procedure. Eating, drinking and smoking should be avoided after midnight the night before the egg collection.

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IVF and Microinjection (ICSI)

IVF: After the eggs are retrieved, they are placed in IVF culture medium and transferred to an incubator to await fertilization by the sperm. Fertilization occurs in the laboratory when the sperm cell penetrates the egg, usually within hours after insemination. 16-24 hours later, the eggs are checked for fertilization. Embryos developed with this procedure are then transferred at the appropriate time into the woman's uterus. 

Since sperm which would  normally not be able to fertilize an egg are used with ICSI, it is greatly advised that any anomalies in the baby be checked when a pregnancy is achieved. Research shows that while anomaly rates are not higher in ICSI babies, there is a two-fold increase in sex -chromosome anomaly rates. Genetic counseling is recommended before ICSI if genetic anomalies passed from father to son are identified . An amniocenteses can also be performed on the fourth month of pregnancy to check for sex-chromosome anomalies.

Overall, pregnancy and delivery rates with ICSI are similar to the rates seen with traditional IVF. The success rates of both techniques depend mostly on the woman's age and the quality of the collected eggs. The eggs of women above the age of 35 having higher incidences of chromosomal anomalies decrease implantation rates and increase miscarriage rates. Some women's ovarian reserve may also be reduced not yielding enough good quality eggs. This, in turn, decreases embryo quality.

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Embryo Transfer

Spotting, caused by the procedure itself is common after embryo transfer. The doctor should be called immediately in cases of abdominal bloating, vomiting or lack of appetite as ovarian hyperstimulation syndrome might be the cause of these symptoms.  

A pregnancy test is done on the tenth to twelfth day after embryo transfer even in cases where the period has started because vaginal bleeding does not mean pregnancy has not occurred. If there are doubts concerning the results of the pregnancy test, a second test may be done 2 days later. Sexual intercourse should be avoided until the results of the tests have been confirmed. Patients whose pregnancy tests come out positive are asked to have a ultrasound ten days later to view the embryonic sac. Since a clinical pregnancy is only accepted when the heart beat is seen, another ultrasound is recommended ten days following the first one.  The patient should consult the doctor before taking any  medication other than the ones prescribed, should stay away from high radiation areas and abstain from smoking as of the first day of the treatment.

If the treatment is unsuccessful, another treatment cycle may be started 2-3 months later.

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Assisted Hatching

A membrane called zona pellucida surrounds the egg and embryo. This membrane normally thins out as the embryo develops and disappears completely, letting the embryo attach to the uterus.  Assisted hatching (AH) is a micromanipulation procedure in which a hole is made in the zona pellucida just prior to embryo transfer to facilitate hatching of the embryo. AH may improve pregnancy rates in older women whose zonas are thicker (women above the age of 35), couples who have failed prior IVF attempts, and in cycles in which thawed embryos are used. This procedure increases pregnancy rates by 10 %. 

At our center, this easy procedure is performed using the laser which is the quickest and safest method which despite being an easy one, requires a great deal of attention. A hole of the required size is drilled by sending laser rays onto the zona. 

Cryopreservation

No equipment is used during the thawing procedure. The media used during freezing are used in a reverse way. The embryos which are brought to room temperature are placed in the most concentrated liquid and their waiting times are carefully monitored. When their temperature reaches 37 degrees, they are placed in incubators. They are then transferred to the woman's uterus on the same day (depending on the stage at which they were frozen) or are made to wait to develop further so that healthy embryos are chosen for transfer. We generally prefer the latter option as the quality of the embryos increase the chance of pregnancy.

Since the freezing and thawing procedures can be traumatic to the embryos, some fragile embryos may not survive the process and  sometimes if no quality embryos remain, the embryo transfer is cancelled.

In addition to that, ovarian tissue and testicular tissue taken during microsurgical procedures can be cryopreserved to be used at a later date.

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Success Rates

The success rates of an IVF center depend on a number of factors, and a comparison of clinic success rates may not be meaningful because patient characteristics and treatment approaches vary from clinic to clinic. For example, the type of patients accepted into the program and the number of embryos transferred per cycle affect the program’s statistics. Statistics calculated on small numbers of cycles may also not be accurate.

An IVF center’s success rates may change dramatically over time, and the compiled statistics may not represent a program’s current success. It is also important to understand the definitions of pregnancy rates and live birth rates. For example, a pregnancy rate of 40% does not mean that 40% of women took babies home. Pregnancy does not always result in live birth, and even the word “pregnancy” has more than one meaning. A biochemical pregnancy is common after IVF. This is a pregnancy confirmed by blood or urine tests but not by ultrasound, because a miscarriage occurs before the pregnancy is far enough along to show up on ultrasound. A clinical pregnancy is one in which the pregnancy is seen with ultrasound, but miscarriage may still occur. Therefore, when comparing the “pregnancy” rates of different clinics, it is important to know which type of pregnancy is being compared.

Most couples are more concerned with a clinic’s live birth rate, which is the probability of delivering a live baby per IVF cycle started. Pregnancy rates, and more importantly live birth rates, are influenced by a number of factors, especially the woman’s age. 

The live birth rate for each IVF cycle started is approximately:

   30% to 35% for women under age 35;

   25% for women ages 35 to 37; 

   15% to 20% for women ages 38 to 40;

   and 6% to 10% for women over 40.   

These rates are the average success rates of international IVF centers.

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