Stimulation of the ovary with fertility drugs to enhance egg production (superovulation)
A woman's eggs develop inside fluid-filled cysts (sacs) inside the ovaries, called follicles. During a natural menstrual cycle in which no fertility drugs are taken, several follicles begin to enlarge around the time when the woman is having her period.
However, over the course of the next few weeks, only one of these follicles develops to maturity, ruptures, and releases its egg during the process of ovulation. The other follicles that had begun to develop stop growing and degenerate (dissolve), therefore, only a small percentage of eggs present in the ovaries are ever ovulated during the woman's reproductive life span.
We can "rescue" follicles and eggs that would otherwise degenerate by giving shots of fertility drugs which contain FSH (follicle stimulating hormone). This is the same hormone that the pituitary gland produces to cause one egg to develop. By increasing the woman's blood level of FSH, several follicles may grow at approximately the same rate allowing us to collect more than one mature egg.
The first fertility drug that most women use causes the pituitary gland to release high amounts of FSH and LH (luteinizing hormone) for several days until its stores are depleted. Since continued use prevents the pituitary gland from producing new supplies of FSH and LH, the amount of these hormones being released per day becomes very low after 7 to 10 days.
The goal that we achieve with the drug is to ensure that blood levels of LH are low during the last few days of follicle growth, since we know that high levels of LH can lead to poor egg quality and stimulate progesterone production by the ovaries. A premature rise in progesterone may cause inappropriate maturation of the uterine lining and lead to a lesser chance of embryo implantation.
When down regulation is achieved another class of drugs called Gonadotrophins are taken daily for 8 to 11 days, depending on how quickly the follicles mature. We can assess the ovarian response to these fertility drugs by measuring the follicle sizes with vaginal ultrasound and by following the increase in production of estradiol (estrogen) and progesterone by the cells inside the follicles.
When the largest follicles reach approximately 18 mm in diameter, the woman takes a shot of hCG (human chorionic gonadotropin - brand name Profasi and Pregnyl). This hormone stimulates the final steps of maturation of the eggs. The egg collection occurs 35 hours after the hCG injection
Collection of mature eggs from the ovary (egg retrieval)
Egg collection is performed under intravenous sedation anesthesia by physician-staffed anesthetist, Embryologist and Nurse in our procedure room. A sterile vaginal ultrasound probe is used to guide a needle through the vaginal wall and into the follicle of the ovary. While long, the needle is not much wider than a needle used to draw blood from an arm vein.
Once the needle is inside the follicle, suction is created which pulls the egg and the fluid through the needle and into a collection tube. When one follicle is drained, the needle is gently repositioned to collect fluid from each adjacent follicle. This is done for both ovaries. The follicular fluid is given to the embryologist, who examines it under a microscope to find the eggs. The entire procedure takes approximately 20 minutes. After one hour of observation in the recovery room, patients are allowed to return to their home or hotel.
Egg Fertilization and Embryo Culture
The male partner provides the laboratory with a semen specimen to be used for fertilization of the eggs, except if donor or frozen sperm is used.
In cases of normal sperm function, the eggs and several thousand sperm are placed together in a dish which contains a culture media. These dishes are kept in an incubator overnight and are examined under the microscope on the morning after the egg retrieval to determine which eggs have fertilized normally.
An alternative method of achieving egg fertilization is called Intracytoplasmic Sperm Injection, or ICSI. An extremely sharp glass needle is used to inject one sperm directly into the center (cytoplasm) of the egg under the guidance of a specially fitted microscope.
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ICSI: Intracytoplasmic sperm injection |
Candidates for ICSI include men with (1) severely compromised sperm parameters, including concentration, motility, morphology, or antisperm antibodies; (2) blockage or absence of the vas deferens, where sperm is surgically collected by epididymal aspiration or testicular biopsy for ICSI; (3) those who had low or failed fertilization on prior IVF attempts; and (4) unknown infertility (causes of couple's infertility remain unknown after completing all diagnostic testing).
The success rate with this technique varies considerably among IVF programs and is highly dependent upon the skill of the embryologist performing the procedure.
One of the most important aspects of a successful IVF cycle is the handling of the eggs and embryos outside of the body. Among our standard protocols is the use of sequential media which is designed to physiologically resemble the environment in the female body. Reproducing the human environment aims to minimize the intracellular stress of the embryo, which is necessary for a positive treatment outcome. Specialized environmental conditions are maintained in the IVF laboratory to eliminate contaminants and volatile substances in the air which may adversely affect embryos.
Traditionally, the majority of embryo transfers are performed after 3 days of culture when the embryos have four to eight cells. A concern with this is that Day 3 embryos normally are found in the fallopian tubes, not in the uterus. The embryo first moves into the uterus at about 78-82 hours after ovulation. The implantation process begins about 3 days later, after blastocyst formation and hatching have occurred.
Many of the embryos on culture day three do not have the biologic potential to develop into high quality blastocysts (Day 5 embryos). Therefore, the trend has been to transfer more embryos on day 3 in an attempt to achieve acceptable pregnancy rates. By choosing the optimal blastocysts for transfer on day 5, we can select the embryos with the highest potential for implanting and making a baby.
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The two pronuclei (small circles in the center of the cell) confirm fertilization of the egg (oocyte) has occurred. |
A two cell embryo. |
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A four cell embryo. |
An eight cell embryo, which is usually seen 72 hours after fertilization. |
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A blastocyst after 5 days of Culture |
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