GLOSSARY OF INFERTILITY TREATMENT

Clomiphene citrate (Clomid®, Serophene®) is an oral medication commonly used for ovulation induction. It makes the brain sense a low estrogen level. The brain responds by increasing the amount of follicle stimulating hormone (FSH) released into the blood stream, with resultant ovarian follicle recruitment and growth.

Each follicle contains an egg. Between one and three tablets of clomiphene citrate are taken starting on cycle day three, four, or five and continued for five days. Ovulation typically occurs between cycle days eleven and seventeen. Intrauterine Inseminations are often performed in conjunction with clomiphene ovulation induction.

In a Gonadotropin cycle the use of follicle stimulating hormone (FSH) injections intramuscularly or subcutaneously results in high levels of FSH circulating in the blood stream. FSH acts directly on ovarian follicles resulting in recruitment and stimulation of many eggs.

Injectable FSH comes from two sources: the urine of post-menopausal women (Repronex, Menopur, and Bravelle {FSH +LH}) and through recombinant DNA technology (Follistim, and Gonal-F). Injectable FSH medication is typically started on the third day of a menstrual period and is continued for approximately ten days. Intrauterine inseminations are frequently used in conjunction with injectable gonadotropins.

Intrauterine insemination (IUI) (also termed artificial insemination) is a fertility procedure in which sperm are washed, concentrated, and injected directly into a woman’s uterus. In natural intercourse, only a fraction of the sperm makes it up to the woman’s fallopian tubes. IUI increases the number of sperm in the fallopian tubes, where fertilization takes place.

IVF involves taking oocytes from the woman, fertilizing them in the lab with sperm and transferring the resulting embryos back to her uterus 2-6 (usually 3-5) days later.

The woman is stimulated with injected medications (FSH or hMG) to stimulate multiple follicles to develop. These injections continue for about 8 – 10 days. Blood and ultrasound testing is done every 1-3 days to monitor the development of the follicles (fluid filled sacs containing oocytes) in the ovaries. When the woman’s follicles are mature, an oocyte (egg) retrieval (egg aspiration) procedure is performed to remove the eggs from the follicles. The eggs are then fertilized in the lab with her partner’s sperm. The embryos are cultured in the lab for 2-6 days.

The embryo transfer procedure is done which places the embryos in the woman’s uterus where they will hopefully implant and develop to result in a live birth. If there are leftover embryos (of sufficient quality) beyond the number that is transferred, many couples prefer to have them frozen (cryopreserved) for use in a future cycle (Frozen Embryo Transfer or FET). Embryo Cryopreservation can be used for another attempt at having a baby if the “fresh” cycle fails – or as an attempt to have another child if the fresh cycle is successful.

ICSI involves injection of single sperm into a single oocyte in order to achieve fertilization in cases of severe male factor infertility. First, the woman must be stimulated with medications and have an oocyte retrieval. The eggs are injected using specially designed microscopes, needles and micromanipulation equipment.

How is ICSI performed?

• The mature egg is held with a specialized holding pipette.
• A very delicate, sharp and hollow needle is used to immobilize and pick up a single sperm.
• This needle is then carefully inserted through the shell and in to the cytoplasm of the egg.
• The sperm is injected in to the cytoplasm and the needle carefully removed.
• The eggs are checked the next morning for evidence of normal fertilization.

Assisted Hatching is a micromanipulation technique in which the shell around the oocyte is opened or thinned to facilitate the embryo hatching process. Assisted hatching involves drilling through the shell using an acid solution or a laser to partially thin an area of the egg, and in some cases create a small hole all the way through the shell.

How is assisted hatching performed?

• The embryo is held with a specialized holding pipette.
• A very delicate, hollow needle is used to expel an acidic solution against the outer “shell” of the embryo.
• A small hole is made in the shell by digesting it with the acidic solution.
• The embryo is then washed and put back in culture in the incubator.
• The embryo transfer procedure is done shortly after the hatching procedure. Embryo transfer places the embryos in the woman’s uterus where they will hopefully implant and develop to result in a live birth.

GIFT stands for Gamete Intra-Fallopian Transfer. Which means male gametes (sperm) and female gametes (eggs) are placed into the fallopian tube where fertilization will take place. Careful monitoring is done to check the response to the medications by trans-vaginal ultrasounds & the measurement of blood estrogen levels. Once the follicles are of appropriate size and the estrogen levels have risen, arrangements are made for the GIFT procedure. GIFT is done either in the hospital or an IVF center containing an operating room.

The eggs are retrieved either trans-vaginally under IV sedation or with a laparoscope under general anesthesia. Once the eggs have been retrieved, they are combined with the washed sperm and immediately placed back into the fallopian tube with a special catheter and a laparoscope under general anesthesia. Usually up to 6 eggs are placed back. The GIFT procedure takes appropriately 60 to 90 minutes. Any extra eggs obtained during the retrieval can be fertilized in the laboratory and frozen for future use.

ZIFT, which stands for Zygote Intra-Fallopian Transfer, is the already fertilized egg or zygote as in IVF, but transferred back into the fallopian tube instead of the uterus. ZIFT is basically the same concept as GIFT in the transfer location of the fallopian tube and in the fertilization of the egg in the laboratory as in IVF.
It was developed to prove fertilization prior to transferring back to the fallopian tube. ZIFT requires the same protocol of fertility medications causing ovary stimulation & monitoring as described in GIFT.

For individuals who undergo IVF and have additional viable embryos after transfer, freezing these embryos increases their opportunity to achieve one or more pregnancies as a result of a single egg retrieval procedure. Usually about 75% of the frozen embryos survive the thawing process, but it will vary depending on when the embryos are frozen.

In the treatment month, a mid-cycle ultrasound is performed to confirm adequate follicle and uterine lining growth. The patient monitors herself for ovulation at home using a home ovulation predictor kit purchased from a pharmacy. When the kit is positive the patient takes a HCG injection and the transfer is performed a few days later. Or the cycle may be assisted by administration of exogenous hormones (e.g. estrogen/progesterone) at specific doses and times to build the endometrial lining in the uterus prior to timed transfer of the frozen embryo/s.

Pre-implantation genetic diagnosis (PGD) is a technology used in conjunction with IVF and includes testing embryos for single gene defects (like cystic fibrosis) or for common chromosome abnormalities (pre-implantation genetic screening or PGS). This type of embryo screening has been shown to be effective in preventing genetic diseases and may improve IVF outcomes although its efficacy for that has yet to be definitely proven.

FISH is a technique used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH is commonly used in prenatal diagnosis and has been used for aneuploidy screening.

Array Comparative Genomic Hybridization (aCGH) is a technique used to evaluate and screen all 23 chromosome pairs of a human embryo cell for abnormalities. In contrast, pre-implantation genetic screening using the FISH technique has only allowed for the evaluation of 9 to 12 chromosomes.

In-vitro Maturation is the technique of helping immature eggs (oocytes) to mature in the laboratory in order to use them for IVF.