IVF & ICSI : A GUIDE TO ASSISTED REPRODUCTIVE TECHNOLOGIES
In order to understand assisted reproduction and how it can help infertile couples, it is important to understand how conception takes place naturally. In order for traditional conception to occur, the man must ejaculate his semen, the fluid containing the sperm, into the woman’s vagina near the time of ovulation, when her ovary releases an egg. Following ovulation, the egg is picked up by one of the fallopian tubes. Since fertilization usually takes place inside the fallopian tube, the man’s sperm must be capable of swimming through the vagina and cervical mucus, up the cervical canal into the uterus, and up into the fallopian tube, where it must attach to and penetrate the egg in order to fertilize it. The fertilized egg continues traveling to the uterus and implants in the uterine lining, where it grows and matures. If all goes well, a child is born approximately nine months later.
In Vitro Fertilization (IVF)
IVF is a method of assisted reproduction in which a man’s sperm and a woman’s eggs are combined outside of the body in a laboratory dish. If fertilization occurs, the resulting embryos are transferred to the woman’s uterus, where one or more may implant in the uterine lining and develop. The basic steps in an IVF treatment cycle are ovarian stimulation, egg retrieval, insemination, fertilization, embryo culture, and embryo transfer.
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. Timing is crucial in an IVF cycle.
The ovaries are evaluated during treatment with vaginal ultrasound examinations to monitor the development of ovarian follicles When the ovaries are ready, hCG or other medications are given. 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 36 hours after the hCG injection is given. However, 10% to 20% of cycles are cancelled prior to the hCG injection. IVF cycles may be cancelled for a variety of reasons, usually due to an inadequate number of follicles developing. Occasionally, a cycle may be cancelled to reduce the risk of severe ovarian hyperstimulation syndrome (OHSS).
Egg retrieval is usually accomplished by transvaginal ultrasound aspiration, a minor surgical procedure that can be performed in the physician’s office or outpatient center. Some form of anesthesia is generally administered. An ultrasound probe is inserted into the vagina to identify the mature follicles, and a needle is guided through the vagina and into the follicles. The eggs are aspirated (removed) from the follicles through the needle connected to a suction device.
Insemination, Fertilization, and Embryo Culture
After the eggs are retrieved, they are examined in the laboratory. The best quality, mature eggs (Figure 4) are placed in IVF culture medium and transferred to an incubator to await fertilization by the sperm. Sperm are separated from the semen in a process known as sperm preparation. Motile sperm are then placed together with the eggs, in a process called insemination, and stored in an incubator. When rates of fertilization are expected to be poor, fertilization may be achieved in the IVF laboratory using specialized micromanipulation techniques. Intracytoplasmic sperm injection (ICSI), which a single sperm is injected directly into the egg in an attempt to achieve fertilization approximately 40% to 70% of the mature eggs will fertilize after insemination or ICSI. Lower rates may occur if the sperm and/or egg quality are poor. Occasionally, fertilization does not occur at all. Two days after the egg retrieval, the fertilized egg has divided to become a 2-to 4-cell embryo. Embryos may be transferred to the uterus at any time between one to six days after the egg retrieval. If successful development continues in the uterus, the embryo hatches from the surrounding zona pellucida and implants into the lining of the uterus approximately six to 10 days after the egg retrieval.
The next step in the IVF process is the embryo transfer. No anesthesia is necessary, although some women may wish to have a mild sedative. The physician identifies the cervix using a vaginal speculum. One or more embryos suspended in a drop of culture medium are drawn into a transfer catheter, a long, thin sterile tube with a syringe on one end. The physician gently guides the tip of the transfer catheter through the cervix and places the fluid containing the embryos into the uterine cavity. The procedure is usually painless, although some women experience mild cramping.
Extra embryos remaining after the embryo transfer may be cryopreserved (frozen) for future transfer. Cryopreservation makes future ART cycles simpler, less expensive, and less invasive than the initial IVF cycle, since the woman does not require ovarian stimulation or egg retrieval. Once frozen, embryos may be stored for several years. However, not all embryos survive the freezing and thawing process, and the live birth rate is lower with cryopreserved embryo transfer. Couples should decide if they are going to cryopreserve extra embryos before undergoing IVF.
It is 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 the pregnancy miscarries before it 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. In general, 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.
Donor sperm, eggs, and embryos
IVF may be done with a couple’s own eggs and sperm or with donor eggs, sperm, or embryos. A couple may choose to use a donor if there is a problem with their own sperm or eggs, or if they have a genetic disease that could be passed on to a child. Donors may be known or anonymous. In most cases, donor sperm is obtained from a sperm bank, and sperm donors undergo extensive medical screening. Donor eggs are an option for women with a uterus who are unlikely or unable to conceive with their own eggs. Egg donation is more complex that sperm donation and is done as part of an IVF procedure. The egg donor must undergo ovarian stimulation and egg retrieval. During this time, the recipient (the woman who will receive the eggs after they are fertilized) receives hormone medications to prepare her uterus for pregnancy. After the retrieval, the donor’s eggs are fertilized by sperm from the recipient’s partner and transferred to the recipient’s uterus.
The recipient will not be genetically related to the child, but she will carry the pregnancy and give birth. In some cases, when both the man and woman are infertile, both donor sperm and eggs have been used. Donor embryos may also be used in these cases.