About the In Vitro Fertilization (IVF) Process
When medical conditions prevent the sperm from reaching the egg, the skilled physicians and laboratory staff are here to assist. Your eggs are retrieved, inseminated in the lab with semen from your partner or a donor, and then inserted back into your uterus as embryos. While every woman’s cycle is unique, the following is a general outline of the steps involved during a cycle of in vitro fertilization.
Step One: Ovulation Induction
Fertility drugs, taken through injections, are used to stimulate a woman’s ovaries to develop multiple mature eggs. This improves chances for fertilization and ultimately pregnancy. The most common medications are gonadotropins including Repronex, Follistim, Gonal F, and Menopur.
Step Two: Egg (Oocyte) Retrieval
When the eggs are mature, they are retrieved by an ultrasound-guided procedure that is performed under light anesthesia on an outpatient basis. During the procedure a needle is placed through the vaginal opening and into the ovaries. There are no abdominal incisions or suturing. The eggs are then evaluated in the onsite embryology lab. Once there, they are fertilized with sperm from your partner or a donor. Risks are minimal and recovery takes an hour or two, although post-operative cramping is common.
Success rates vary depending on a woman’s age, her response to the medication and the quality of her embryos. Risks include increased chances of multiple births and ovarian hyperstimulation. The chances of infection or significant blood loss are very low.
Step Three: Fertilization in the Lab
Once the eggs arrive in the embryology lab, the skilled staff analyzes them for maturity and then incubates them. At this time, partners are asked to collect a fresh sperm sample, which is then analyzed and treated to isolate the best sperm for insemination. The sperm is then mixed with the eggs or injected directly into the eggs using intracytoplasmic sperm injection (ICSI).
It takes approximately 18 hours to determine if fertilization has occurred and 24 to 72 hours to establish if the embryo is growing. During a successful IVF process, the oocytes and embryos will stay in the laboratory for approximately 2 to 5 days.
Step Four: Embryo Transfer
A few days after the oocytes are retrieved and fertilized in the laboratory, you will come to the office for the embryo transfer procedure. Embryo transfer is a simple technique and anesthesia is not required. On the day of transfer, you, your partner, and our specialist will discuss the number of embryos being transferred, as well as their quality and grade.
During the actual procedure, a long, thin catheter containing the embryos and a small amount of fluid is passed through your cervix into your uterus, where the embryos are placed.
Conventional embryo transfer is performed three days after the donor’s egg retrieval when healthy embryos (Day 3 embryos) reach the 6-8 cell stage. Blastocysts are embryos that have advanced to 30-60 cells and are transferred five days after retrieval.
If you have a large number of good quality embryos on day 3, the doctor may recommend that you wait 2 days and have a blastocyst transfer on day 5. During the two additional days, some embryos will not progress and others should continue to develop. It is felt that the embryos that survive and progress during this time will be most likely to survive in the uterus. Thus, blastocyst culture is a tool that allows the embryologists and physicians to select the “best” embryos for transfer.
Additionally, blastocyst transfer allows the number of embryos transferred to be kept to a minimum, which reduces the chance for multiple births, while still giving you an excellent chance for conceiving. Transfer on day 3 is still recommended if there are a low number of “good” embryos on day 3.
Following the embryo transfer, you must limit certain activities and continue required medications. In five days, a blood test is done to monitor your hormone levels. A pregnancy test is taken 9 to 11 days after the embryo transfer, and will determine whether the procedure was successful.
Sometimes during the IVF process extra embryos develop during your cycle. If the embryos are of acceptable quality, they can be frozen and stored for future transfer. Since the IVF process can be difficult both physically and financially, cryopreservation helps facilitate treatment of infertility while also reducing the cost.
Intracytoplasmic Sperm Injection (ICSI)
Intracytoplasmic Sperm Injection, or ICSI, is a micromanipulation procedure that involves injecting a single sperm into the center of an egg. This method of fertilization can be particularly effective in cases of male infertility resulting from obstructive azoospermia (meaning cases where sperm cannot pass from the testis out the penis) or those where the semen has low sperm parameters such as low counts or low motility. For obstructive cases, microsurgical techniques and laboratory expertise combine to extract sperm directly from the testis or epididymus for use with ICSI,
Embryo Quality and Grading
The majority of embryos produced in the laboratory are cultured for 5 days after egg harvest. As embryos develop, they are closely watched by the embryologists and each is assigned a grade. Labs use the Gardner system to grade 5-day old blastocysts which uses the ranking AA-quality (considered the best and rarely seen in the laboratory) to DD-quality (those felt unsuitable for transfer). Day-3 embryos are ranked by the number of cells that are present along with a score from 1 to 4 (1-best, 4-worst). When you arrive for your embryo transfer, the physician will go over the number of embryos you have, the grade of each and make a recommendation, based on input from our embryologists, as to which embryos should be transferred and how many. The doctors try to adhere strictly to the American Society of Reproductive Medicine’s guidelines regarding the number of embryos transferred.
Please note that there is no standard classification system used by all fertility centers. Although most centers use the Gardner grading system for blastocysts, each center created their own system for grading day-2 and 3 embryos as the technology developed and, at this point, it would be too difficult for all centers to try and use a standard grading method.
During cell division, little pieces may break off and result in a fragmented embryo. A small amount of fragmentation is normal, but as the degree of fragmentation increases the odds of successful implantation are diminished. In fact, significant fragmentation has been associated with chromosomally abnormal embryos. All embryos evaluated in the lab are assigned a fragmentation score by estimating the percentage of the embryo volume that is replaced by fragments. Up to 10% fragmentation is considered good quality, 10-20% is okay and embryos with more than 20% fragmentation are considered suboptimal. While a successful pregnancy can be achieved with a fragmented embryo, the odds decrease as fragmentation increases.
What Happens After an Embryo Transfer?
Once you complete your embryo transfer, you will have approximately 1½ weeks to wait before a pregnancy can be detected. The following tables outline an approximate timeline for what happens during a successful pregnancy after a 3-day transfer (3dt) and a 5-day transfer (5dt).
|One||The embryo continues to grow and develop, turning from a 6-8 cell embryo into a morula|
|Two||The cells of the morula continue to divide, developing into a blastocyst|
|Three||The blastocyst begins to hatch out of its shell|
|Four||The blastocyst continues to hatch out of its shell and begins to attach itself to the uterus|
|Five||The blastocyst attaches deeper into the uterine lining, beginning implantation|
|Seven||Implantation is complete, cells that will eventually become the placenta and fetus have begun to develop|
|Eight||Human chorionic gonadotropin (hCG) starts to enter the blood stream|
|Nine||Fetal development continues and hCG continues to be secreted|
|Ten||Fetal development continues and hCG continues to be secreted|
|Eleven||Levels of hCG are now high enough to detect a pregnancy|
|One||The blastocyst begins to hatch out of its shell|
|Two||The blastocyst continues to hatch out of its shell and begins to attach itself to the uterus|
|Three||The blastocyst attaches deeper into the uterine lining, beginning implantation|
|Five||Implantation is complete, cells that will eventually become the placenta and fetus have begun to develop|
|Six||Human chorionic gonadotropin (hCG) starts to enter the blood stream|
|Seven||Fetal development continues and hCG continues to be secreted|
|Eight||Fetal development continues and hCG continues to be secreted|
|Nine||Levels of hCG are now high enough to detect a pregnancy|