Treatment Options and Risks

ARTs		Side Effects/Risks
Ovulation Induction (OI)		Multiple Pregnancy
IUI		Ovarian Hyperstimulation
GIFT		Negative Reactions to Medications/ Infection
ZIFT
In-Vitro Fertilization
ICSI
SUZI

TYPES OF ASSISTED REPRODUCTIVE TREATMENTS (ARTs)

1: Ovulation Induction (OI) and Timed Intercourse

This treatment is often used when women have problems with ovulation. Drugs which stimulate ovulation could be given as tablets (Clomid) or injections (Gonadotrophin). The procedure is monitored through the use of ultrasound scans. At the proper time, ovulation is induced with Human Chorionic Gonadotropin (HCG) hormone. The couple can then be advised to proceed with sexual intercourse.


	Assessment of Size and Number of Ovarian Follicles		Assessment of Endometrial Thickness

2: Artificial Insemination/ Intrauterine Insemination (IUI)

This treatment is recommended when women have problems with ovulation, when men exhibit mild male factor infertility, when the couple's reasons for infertility remain unexplained, or when the couple is unable to have normal intercourse. In IUI the ovaries are stimulated with hormone tablets (clomiphene) and gonadotropin injections (FSH), in order to allow more than one follicle to develop. If several follicles develop and mature, they will each release an ovum. Therefore, the probability of fertilization increases due to the presence of a greater number of ova. Men are asked to produce a sperm sample, which is usually processed. During processing, the sperm is removed from the seminal fluid, and often the most active and motile sperm are separated and concentrated. The sperm concentrate is then injected into the uterine cavity through the cervix by using a catheter at the time of ovulation.

IUI

3: Gamete Intra-Fallopian Transfer (GIFT)

GIFT is used in couples who have unexplained infertility, but who have proven fertility from a previous pregnancy or during IVF. During this procedure, the gametes (sperm and eggs) are injected into the Fallopian tubes. In order for this treatment to take place, both sperm and eggs have to be collected. The men are asked to donate a sperm sample, and this sample is processed in a way that concentrates healthy and normal sperm. The eggs of the woman are usually collected vaginally. In order for this to take place, the female is first given hormonal injections to stimulate follicular development. This will help the doctor aspirate a greater number of eggs during the egg retrieval procedure. In order for egg retrieval to take place, the woman is usually placed under anaesthesia or is sedated. A vaginal ultrasound probe with an attached aspiration needle is inserted through the vagina and into the follicles of the ovary. The fluid within each follicle is then aspirated into a test tube, and the tubes are sent to the lab in order for the eggs to be recovered and isolated. The desired number of eggs and sperm are then placed in a catheter and injected into a Fallopian tube. In order for GIFT to take place, the woman is usually placed under general anaesthesia since the transfer procedure is done through laparoscopic surgery.

GIFT

4: Zygote Intra-Fallopian Transfer (ZIFT)

ZIFT is similar to GIFT, except in this procedure zygotes instead of gametes are transferred into the Fallopian tubes. The main advantage of ZIFT is that it uses fertilized eggs, therefore, in comparison to GIFT it is one step closer to pregnancy. During this procedure the man's semen is again collected and processed. The female undergoes ovarian stimulation and the egg retrieval procedure. The eggs and sperm that have been collected are then placed in a petri dish inside an incubator until fertilization takes place. Using laparoscopy, the resulting zygotes are then transferred to the Fallopian tubes with a catheter.

ZIFT

5:In-Vitro Fertilization (IVF)

IVF is often divided into four main steps:

1. Ovulation Induction
2. Oocyte (Egg) Retrieval
3. Insemination and Fertilization
4. Embryo Transfer

IVF is often used when women have occluded or absent Fallopian tubes. This treatment is also used when other ARTs, such as GIFT, IUI, and OI, failed to result in pregnancy. Often before beginning IVF, the male and female are required to undergo a screening process. The female is usually asked to provide blood for routine lab investigations. In addition, the woman will usually have a trans-vaginal ultrasound to evaluate the thickness of the endometrial lining, the curvature of the cervix, the position of the uterus, and the ovaries. Often a mock-embryo transfer is conducted to measure the depth of the uterine cavity.

IVF

1. Ovulation Induction:

Ovulation induction is the process by which the ovaries are stimulated, so that multiple follicles are produced. In the month before ovulation induction, the woman is given oral contraceptives. The purpose of the contraceptives is to prevent ovarian cyst formation. A few days before finishing the oral contraceptives, the patient is administered certain drugs that help 'turn off' or reset the individuals normal menstrual cycle. At around the time of menstruation, the patient is required to take a blood test and have an ultrasound. The blood test helps measure the estrogen in the blood and determine if it is at the proper level. The ultrasound helps ensure that ovarian cysts are absent. If both these test are in order, the stimulation protocol can begin. Gonadotropin injections are taken either once or twice a day after the menstrual period. These gonadotropins will allow several follicles to develop and enlarge (in natural cycles only one follicle releases an ovum). Each woman responds to gonadotropins differently, and therefore in each individual case the dose administered may vary. When ultrasound examination and blood estrogen levels reveal that the follicles are large enough one injection of another hormone called HCG is given to the patient to prepare the egg for ovulation. It is then necessary to proceed with egg retrieval 35 hours after the HCG injection.


	Stimulating Follicular Growth by Injections		Ultrasound for Monitoring Follicular Growth		Vaginal Ultrasound Monitoring Ovulation Induction

2. Egg Retrieval :

The woman needs to be fasting for 8 hours before the procedure. The egg retrieval should take place exactly 36 hours after administration of the HCG injection. The procedure is performed as a day case surgery under a general anaesthetic. A vaginal probe with an attached aspiration needle is used to puncture each follicle and retrieve the fluid and eggs. The entire procedure and is usually completed within half an hour. Furthermore, recovery is fairly rapid. The woman may feel some cramping, heaviness, soreness, and there may be some spotting. However, after two hours or less the patient is usually able to return home. When the patient returns home, she should relax and refrain from sexual intercourse for a week. Finally, alcohol and caffeine should not be consumed during this time period.

The male will be asked to produce a sperm sample on the day of the egg retrieval. He should ensure that he has not ejaculated for 2 to 5 days before this donation. The sperm is removed from the seminal fluid, and then the healthiest and most motile sperm are concentrated.

The couple should be available for contact at all times following this procedure until the time of embryo transfer.


	Needle Insertedinto Follicle to Aspirate Egg		Aspirated Egg in Test Tube		Checking Presence of Egg via Microscope		Egg Placed in Incubator

3. Insemination and Fertilization

After the egg retrieval is completed, the eggs are left to mature in a Petri dish containing a special media for several hours then the sperm that was collected from the male is usually added to the Petri dish containing the eggs (insemination). The Petri dish is then placed in an incubator in order to allow fertilization and cleavage to take place. Fertilization occurs when the sperm penetrates the egg, forming a single cell with 2 pro-nuclei (one from the egg and from the sperm) called a zygote. The two pro-nuclei will then fuse. The embryo will then undergo cleavage (division). The 4-cell stage usually can be seen approximately 36-48 hours after fertilization, and the 8-cell stage can be seen approximately 72 hours after fertilization. The embryo is transferred to the uterine cavity after 3 days, or when the 8-cell stage is observed in the laboratory by microscopy. Recently, new technology and culture media has enabled doctors to transfer embryos that have reached the blastocyst stage, 5-6 days after fertilization.


	Sperm Surrounding the Egg		Single Sperm Fertilizing the Egg

4. Embryo Transfer

The Embryo Transfer usually takes place approximately three days after egg retrieval. This procedure is not performed under anesthesia. It is recommended that the patient comes with her bladder half-full since this helps facilitates the transfer procedure. The doctor will consult the couple, and will present them with information regarding the number and quality of the embryos available for transfer. Together, they will decide on the number to be transferred. The remaining embryos can then be preserved or discarded.

For the procedure, the patient will be asked to lay on her back. A catheter with a long, flexible, thin tube is used to transfer the embryos under the guidance of an ultrasound. The catheter is inserted through the cervix and the embryos are injected into the uterus. The catheter is then given to the lab, and is checked microscopically to ensure that all the embryos have been transferred. The patient will then be requested to rest for 60 minutes after the embryo transfer.

Following the procedure a progesterone supplement (tablets, vaginal suppositories or injections) is prescribed to help support the pregnancy. If the patient requires this supplement, it will be taken throughout the next two weeks and during early pregnancy.

The patient will be asked to take a blood pregnancy test two weeks after the embryo transfer. If the results of the test turn out to be positive, another blood pregnancy test will be taken two days later. A doubling of the beta-HCG value is usually an indication that implantation has occurred. If the second blood test shows a doubling in this hormone's level, this is referred to as a biochemical pregnancy. An ultrasound is required two to four weeks after the first blood test to actually confirm true pregnancy (clinical pregnancy with a pregnancy sac inside the uterine cavity).


	Identification and Loading of Embryos into a Catheter		Embryo Transfer

Inverted Microscope used for ICSI

6: Intra-Cytoplasmic Sperm Injection (ICSI)

ICSI is a procedure used for couples where men have proven to have severe infertility. The male may have a very low sperm count, a high percentage of abnormal sperm, or sperm that is immotile. This treatment is also recommended for couples that did not fare successfully during the egg retrieval process. If only a few eggs were collected from the female, it is often wiser to use ICSI to ensure fertilization. During ICSI, a single sperm is injected into the egg's cytoplasm. The procedure requires extremely advanced microscopes with micromanipulation devices (microinjections and micropipettes). The sperm's tail is cut off to prevent the possibility of movement. The egg is then held in place, while the sperm is inserted into its cytoplasm.


	Needle Piercing Shell of Egg		Injecting Sperm into Cytoplasm of Egg

7: Sub-Zonal Insemination (SUZI)

This procedure is recommended for patients with sperm male factor infertility. During this procedure, a sperm cell is injected directly under the zona pellucida (the outer protein matrix of the ovum).

SUZI

Side Effects/Risks

1: Multiple Pregnancy

The probability of multiple pregnancies occurring during these assisted conception treatments is approximately 20-30%. This incidence rate usually pertains to twin pregnancies, however, higher order pregnancies have happened in the past. If the mother is found to carry triplets or more, then the risks to the mother and children increases. As a result, a patient may be advised to undergo an embryo reduction.

Ultrasound of Triplets

2: Ovarian Hyperstimulation

During Ovulation Induction (OI), the ovaries are stimulated by medication to produce numerous follicles. In some women (20%), an extremely large number of follicles develop (24 or more). Women who suffer from polycystic ovaries (POCD) are especially at risk. The ovaries become extremely large, and the patient will feel very uncomfortable. If this problem arises, the patient is advised to see her physician.

Ovarian Hyperstimulation by Ultrasound
Showing a Large Number of Follicles in Each Ovary

3: Negative Reactions to Medications/ Infection

During the screening and treatment process, a patient may develop an allergic reaction to a certain medication. For example, although this is rare, some patients have an allergic reaction to the iodine used during the HSG. Also, repeated intramuscular injections can sometimes cause redness, pain, and irritation. A patient should immediately contact their physician if they are faced with excessive pain or a severe allergic reaction to any of the medications used. Any surgical procedure may result in an infection. At Hayat, measures are taken to ensure that all equipment is properly sterilized, and that the utmost care is used while handling patients. In certain procedures, such as the egg retrieval, antibiotics are administered intravenously to prevent infection. Even though doctors always use extreme caution, infections can and do happen. Therefore, if a patient experiences pain, discomfort, or unexplained bleeding, they must contact their physician immediately.