Understanding Infertility
The IVF Process
After all fertility testing is finished and the initial IVF consult is over, the IVF process begins. Some doctors will have the women on birth control for a few days or weeks to time the cycle, suppress the ovaries and follicles so that they grow together, or decrease a chance for cysts if there is a history of them.
IVF Medications
Once the period arrives, stimulation shots begin. These begin on day 3 of your cycle and can include:
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Follicle-stimulating hormone (FSH) such as Bravelle, Follistim, or Gonal-F
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Human menopausal gonadotropins (hMG) – a mix of FSH and luteinizing hormone (LH) such as Menopur or Repronex
Also included may be drugs to prevent premature ovulation, such as:
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Gonadotropin-releasing hormone (GnRH) agonists, such as Lupron, Zoladex or Synarel (a nasal spray)
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GnRH antagonists such as Ganirelix or Cetrotide
These (minus Synarel) are all shots given to either the stomach area or thigh area. Possible side effects include:
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Hot flashes
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Bloating
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Headaches
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Bruising and tenderness
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Irritability
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Breast tenderness
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Ovarian hyperstimulation syndrome (OHSS)
Included may be a combination of oral tablets of estrogen and progesterone, vitamins, ovulation drugs and others. Your RE will decide which drugs to use based on the severity of your case.[1][2]
Monitoring
During the 8-14 days of injectable shots, the RE will keep close eye on the ovary growth and number of follicles. This can be seen through transvaginal ultrasound and bloodwork.
As the goal of IVF is to collect as many eggs as possible for better chances, doctors will want to see over 10 follicles growing. Additionally, the uterine lining will need to be growing as well if a transfer is scheduled.[3]
Egg Retrieval
Based on the size of the majority of your follicles (between 18-22 mm), egg retrieval will be schedules. Your RE will instruct you to do a “trigger shot” – a shot of human chorionic gonadotropin (HCG) – to prepare the ovaries to ovulate on time. This trigger shot is timed 36 hours before your scheduled retrieval and must be taken on time.[4]
It is also important not to eat or drink after midnight the night before retrieval as the procedure includes anesthesia. When the woman arrives on her scheduled retrieval day, she will be taken to receive an IV. When the time comes, she will be taken to a special procedure room. After inserting a “duck” (speculum) and cleaning the vaginal area, the woman is put to sleep so retrieval can begin.
While under, the RE will use a transvaginal ultrasound wand to see the ovaries. Attached to the wand is an aspiration needle. This needle is used to penetrate the vaginal wall and enter the follicles to remove the egg and fluid within each follicle. When all possible follicles are drained, the “duck” is removed, the vaginal area is once again cleaned, and the patient is taken to the recovery room. A typical retrieval takes 10-20 minutes only.[5][6]
(Video here)
After waking from anesthesia, pain and nausea are possible. It is best to take the day off of work to rest, but it should subside within a day or two.After the eggs have been retrieved, they are fertilized with the male’s sperm either naturally or using intracytoplasmic sperm injection (ICSI). In ICSI, an embryologist chooses a single sperm and inserts it into the egg via a thin needle. The embryos are then left to hopefully fertilize in an incubator overnight.
The "Embryo Hunger Games"
Colloquially called the “embryo hunger games” in some IVF circles, this is the time from fertilization to transfer.
During this time, eggs must fertilize and keep dividing to be viable. Unfortunately, the number of eggs retrieved will not equal the number of embryos created. Eggs may be immature or unusable, eggs may not fertilize, or embryos may stop growing (called “Arresting”). One study from 1993 saw a 71.2% fertilization rate using ICSI, while a 2003 study saw a 69.6% fertilization rate.[7][8]
Thus, “may the odds be ever in your favor.”
Embryo Grading
Day 3 Embryos
When embryos reach day 3, they are then “graded.” A day 3 embryo will need to be within 7-10 cells to have the best chances to keep growing or become a pregnancy. A number grade from 1-4 is also given based on cell fragmentation within the embryo.
Grade 1
Equal size cells, no fragmentation
2
Equal size cells, minor fragmentation
2.5
Mostly equal size cells, moderate fragmentation
3
Unequal size cells, moderate fragmentation
4
Equal or unequal size cells, but heavy fragmentation
The chances of continued growth or success are usually higher with grade 1-2.5.[9]
Day 5 Embryos
A day 4 embryo is called a “morula”, while a day 5 embryo is called a “blastocyst” or “blast” or short. The embryos that have become a blast by day 5 or 6 have the best chances for success. These embryos are graded with two letters from A-C depending on inner cell mass and the trophectoderm (cells that line the embryo walls to connect with the uterus.)
INNER CELL MASS
Grade A
Pronounced cell mass
B
Visible mass, but not as pronounced
C
Almost non-existent mass
TROPHECTODERM
Grade A
High amount of cells around the walls
B
Average amount of cells around the walls
C
Low amount of cells around the walls
“AA” is the goal as these embryos have the best chances for success – but other blasts still have a chance even if they’re not “perfect.”[10]
Whether doing a 3-day transfer or a 5-day transfer, remaining embryos must be either transferred back to the uterus or cryopreserved for future chances.
Fresh Embryo Transfer
Depending on the clinic, embryos numbers and grades, or patient condition, fresh transfer is possible from days 2-5. After retrieval, the patient will come back on the specified day for transfer. Some studies have showed that day 5 transfer is better[11], but other studies have shown that day 3 and day 5 transfers are comparable with pregnancy rates.[12][13]
Transfer is a simple process in which a transvaginal ultrasound wand guides a catheter to place the embryos into the uterus. Usually an RE will transfer only 1 embryos to prevent multiples, but 2 or 3 is possible depending on the situation. The patient will then rest for about an hour before being released.[14]
The TWW
TWW stands for “Two Week Wait” – the time between transfer and beta. During this time, various medication must be taken to try and support a pregnancy. These can include:
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Estrogen (via oral tablets)
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Progesterone (via oral tablets, progesterone in oil (PIO) shots, or vaginal suppositories)
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Blood thinners (via oral tablets of baby aspirin or shots such as Heparin)
As the body isn’t making these itself, medication must be taken to supplement.
Beta
“Beta” is the blood test at the end of the TWW to confirm pregnancy. If HCG in the blood is greater than 10, IVF has succeeded. If it is lower, a pregnancy has not been achieved and a period will come a few days after stopping medications.
If the cycle resulted in cryopreserved embryos, a FET can be scheduled for a later date. If not, IVF can be started again. For more information on FET, please visit the page in the menu above.
[1] “Infertility Medications.” n.d. American Pregnancy Association. Accessed April 30, 2018. http://americanpregnancy.org/infertility/infertility-medications/.
[2] SCRC Contributor. 2016. “Side Effects of IVF Medication.” Southern California Reproductive Center. 2016. https://blog.scrcivf.com/side-effects-of-ivf-medication.
[3] “IVF Process: Getting Started.” n.d. Shady Grove Fertility. Accessed April 30, 2018. https://www.shadygrovefertility.com/resources/educational-resources/articles/ivf-process.
[4] Sher, Geoffrey. 2016. “The IVF Trigger Shot.” Sher Fertility. 2016. https://haveababy.com/fertility-information/ivf-authority/ivf-trigger-shot-important-determinant-egg-quality.
[5] “Egg Retrieval Process.” 2018. University of Iowa Hospitals and Clinics. 2018. https://uihc.org/health-library/egg-retrieval-process.
[6] “Step 3 - Egg Retrieval.” n.d. Center for Reproductive Health. Accessed April 30, 2018. http://www.fertilitydoctor.net/step-3-egg-retrieval/.
[7] Steirteghem, André C. Van, Zsolt Nagy, Hubert Joris, Jiaen Liu, Catherine Staessen, Johan Smitz, Arjoko Wisanto, and Paul Devroey. 1993. “High Fertilization and Implantation Rates after Intracytoplasmic Sperm Injection.” Human Reproduction 8 (7). Oxford University Press: 1061–66. https://doi.org/10.1093/oxfordjournals.humrep.a138192.
[8] Kably Ambe, Alberto, Julián Ruiz Anguas, José Antonio Garzón Núñez, Everardo Anta Jaen, and Esperanza Carballo Mondragón. 2003. “[Fertilization Rate Analysis as a Predictive Variable for an in-Vitro Fertilization Program Success].” Ginecologia y Obstetricia de Mexico 71 (January): 16–24. http://www.ncbi.nlm.nih.gov/pubmed/12708346.
[9] “Understanding Embryo Grading.” n.d. ARC Fertility. Accessed April 30, 2018. https://www.arcfertility.com/understanding-embryo-grading/.
[10] Tucker, Michael J., and Eugene Katz. 2017. “Embryo Grading.” Shady Grove Fertility. 2017. https://www.shadygrovefertility.com/treatments-success/advanced-treatments/in-vitro-fertilization-ivf/embryo-grading.
[11] Milki, Amin A, Mary D Hinckley, Jeffrey D Fisch, Daniel Dasig, and Barry Behr. 2000. “Comparison of Blastocyst Transfer with Day 3 Embryo Transfer in Similar Patient Populations.” Fertility and Sterility 73 (1). Elsevier: 126–29. https://doi.org/10.1016/S0015-0282(99)00485-9.
[12] Bungum, M, L Bungum, P Humaidan, and C Yding Andersen. n.d. “Day 3 versus Day 5 Embryo Transfer: A Prospective Randomized Study.” Reproductive Biomedicine Online 7 (1): 98–104. Accessed May 1, 2018. http://www.ncbi.nlm.nih.gov/pubmed/12930586.
[13] Coskun, Serdar, Johannes Hollanders, Saad Al-Hassan, Hamad Al-Sufyan, Hend Al-Mayman, and Kamal Jaroudi. 2000. “Day 5 versus Day 3 Embryo Transfer: A Controlled Randomized Trial.” Human Reproduction 15 (9). Oxford University Press: 1947–52. https://doi.org/10.1093/humrep/15.9.1947.
[14] SCRC Contributor. 2016. “Embryo Transfer: What to Expect After the Procedure.” Southern California Reproductive Center. 2016. https://blog.scrcivf.com/embryo-transfer-what-to-expect-after-the-procedure.