This overview summarizes some of the steps an IVF patient undergoes while undergoing an IVF cycle in our program at PFCLA.
- After the initial visit with the physician and after all of the testing is completed, the patient is instructed to call with her period to start the IVF cycle. This initial phase can take up to 2-4 weeks to complete.Once the patient calls on the first day of her period, she is typically instructed to start taking birth control pills (BCP), one pill a day, and wait for instructions.
- In about 7-10 days, the patient will receive a packet by mail or email, that contains all the information that she needs. At the same time, the Clinical Coordinator would have contacted her to arrange for the delivery of the medications that the patient will use. We can either send a prescription for all the medications or have an associated pharmacy ship all the medications with the syringes and needles.
- Once the Calendar packet is with the patient, our office will contact her to make the necessary appointments. These usually include 3 initial appointments:
- Calendar review and injection instruction appointment with a nurse. This can be done by telephone if the patient is not local.
- A baseline ultrasound or Estradiol test prior to the start of the fertility hormones. Again can be done locally if the patient is not within reasonable driving distance from our office.
- Another ultrasound examination with the doctor 6-7 day after the start of fertility hormone. The ultrasound appointments usually take 15-30 minutes. It is during this examination that the doctor determines the number and size of follicles present. Typically, another 1-2 ultrasound examinations will be required before the eggs are ready for harvesting. It takes usually 5-6 weeks after the start of BCPs for the patient to be ready for egg retrieval (ER).
- The ER is performed under anesthesia and takes about 10-20 minutes.
- The patient is then discharged home an hour later. The day of the ER, the partner has to produce a semen sample. The sperm is washed and prepped and used to fertilize all the eggs on the same day, usually within 4-5 hours after retrieval. The number of eggs produced depends on many factors, including the patient age and her ovarian reserve. In general, women < 35, produce between 10-20 eggs. The younger the woman, the more eggs are produced. Women in their late 30s or early 40s, typically produced < 10 eggs. It is also important to understand that usually, the higher the number of eggs produced, the better the chances of pregnancy.
- Fertilization of the eggs is performed on the day of egg retrieval by two methods, depending on many factors including the sperm and egg quality.
- The first method, which is much simpler and less complicated, involves incubating the eggs with concentrated sperm in a Petri dish in an incubator. The second more high tech and complicated method is the ICSI or intracytoplasmic sperm injection method, whereby each egg is injected with a single healthy looking sperm to increase the rate of fertilization. ICSI is sometimes the only mean to achieve fertilization, especially in severe male factor cases.
- The morning after the ER, the embryologist checks the status of the eggs to determine the fertilization status. Not every egg gets fertilize.
- Typically we expect 60-80% fertilization rate. After this brief evaluation, the embryo are placed back into the incubator and left undisturbed until the embryo transfer, which usually takes place 3 to 5 days after the ER.
- The day before the embryo transfer (ET); our office will contact the patient to schedule a time for the ET the next morning.
- The morning of ET, the embryologist would evaluate the embryos and grade them. The doctor will then meet with the patient and review the status of the embryos with the patient and together decide which embryo to transfer. The number of embryo to be transferred depends on many factors, namely:
- Age of the patient producing the eggs
- The quality of the embryos at the hand
- Previous history of failed IVF cycles
- The desire of the patient for multiple births
- The grading of embryos varies from one clinic to the next. In our program, we use two criteria to grade embryos:
- The number of cells
- The percentage of fragmentation
- An embryo is formed when sperm and egg unite.
- Over the next few days, the embryo which started from 2 cells, will divide into multiple cells. On the 3rd day after ER, a competent embryo would have divided to more than 6 cells. We also evaluate each cell’s fragmentation, which in simple term is analogous with the cracking of a mirror. If more than 20% of the surface of an embryo is involved with fragmentation, then the embryo is graded as GIII. A totally clear and unfragmented embryo would be grade as GI or excellent. Good or GII embryos would have 0-20% fragmentation.
- Therefore, when we evaluate an embryo, we would label it by its cell number and then it grading. For instance, an excellent embryo would be 8cell GI, a good embryo would be a 7 or 8 cell GII and a poor quality embryo would be any embryo that is less than 5 cells or with GIII grading.
The majority of our patients, undergo embryo transfer on the 5th day after egg retrieval. On this day, embryos have developed into blastocyst.
The majority of our patients, undergo embryo transfer on the 5th day after egg retrieval. On this day, embryos have developed into blastocyst. The grading we use for blastocyst is as follows:
- Expanded Blast I - A+
- Expanded Blast II - A
- Expanded Blast III - C
- Blast I - B+
- Blast II - B
- Blast III - D
- Early Blast I - B
- Early Blast II - C
- Early Blast III - D
- C/M - F
- 2-8 cells - F
The importance of this grading lies in the fact that pregnancy rates are fairly well correlated with embryo quality. However, we have seen many instances where a patient will conceive and have a healthy child despite the fact that poor quality embryos were transferred. It is also important to note that poor quality embryos do not result in abnormal babies. There is no good data to date to support an ill effect from poor embryos. Bad embryos simply do not attach or are miscarried very early in gestation.
In general, the older the patient, the higher the number of embryos that we would transfer. For instance, in young <30 yo patient or in cases where a young egg donor is used, we would transfer 2-3 good quality embryos. On the other hand, in women in their late 30s, it is not unusual to transfer 5-6 embryos.
The pregnancy rates obviously also depend on many factors, including the quality of the transferred embryos. Please check our statistics for actual numbers based on patient age group. Obviously, pregnancy rates are higher in younger women because of younger and better embryos.
Please note that even after the ER the patient will continue taking medication including prenatal vitamins and Progesterone. This latter hormone is crucial to assist in sustaining a pregnancy. Progesterone is usually taken until the pregnancy test unless the patient conceives, in which case, we will continue until 10 weeks of gestation. Regardless of what the medication insert says, Progesterone is safe during pregnancy.
It is very common for a patient to have multiple embryos and after transferring 1-2, to have embryos to freeze. We typically freeze embryos the day of the ET. We do not recommend freezing poor quality embryo however. Embryos can be frozen for an indefinite amount of time and we have had babies born many years after a freeze. There are disadvantages however with freezing embryos. One of these is the fact that some embryos do not withstand the freezing and thawing process very well. In general, 60-70% of good quality embryos would survive a thaw; therefore it is inevitable to lose embryos after freezing. Pregnancy rates after thawing frozen are less than fresh IVF cycles for many reasons. First, usually embryos that are frozen are not the bet quality ones, as the good ones are typically transferred during the fresh cycle. Second, as mentioned, the freezing and thawing can damage certain embryos and therefore interfere with its success. It is often worth it however to use frozen embryos since it is much less expensive to do a frozen IVF cycle and it involves much less medications.
The embryo transfer is a very simple procedure that takes few minutes. The patient is discharged home one hour later and is asked to lie down for the next 24 hours. Staying in bed for longer has never been shown to improve pregnancy rates! On the other hand, we ask the patient to abstain from strenuous activities or exercise until the pregnancy test, which is performed 10 days after the ET. The test called hCG, is a simple but accurate blood test which measures the amount of pregnancy hormone (hCG) produced by a developing placenta and fetus. The earliest we can detect it in blood is 7-8 day after ET. We like to do it on the 10th day to lower the chances of false positives and false negatives. A healthy hCG level on the 10th day is any level >100. We typically will not repeat the test if the level is >100. If the level is <100, then we would recommend repeating the test 2 day later to see that the level is going up adequately. In healthy pregnancy with day 10 levels of <100, the hCG level will MORE than double. However, there are instances (including our own experience) where a low level of hCG is followed by a less than adequate increase 2 day later and yet resulted in a healthy pregnancy. Therefore, we are hesitant to discontinue any medications until we are 100% certain that the pregnancy is not a normal one. We therefore often repeat multiple levels of hCG over several days until the pregnancy declares itself one way or the other. The level of hCG also gives us a hint on the number of fetuses growing. Levels between 150-200 usually indicate twins and levels over 250 usually indicate the presence of high order multiples such as triplets or quadruplets.
It is not until the first obstetrical ultrasound that we will be able to determine how many “babies” exist.
This first ultrasound is performed at 6 weeks of gestation or 4 weeks after embryo transfer. The determination of gestational weeks is confusing to most patients. In obstetrics, weeks of gestation is calculated usually from the start of a menstrual period. Since in IVF cycles, we control the period, and since in general the menstrual period occurs 2 weeks before ovulation, which is equivalent to egg retrieval, we calculate today’s gestational age by adding 2 weeks to the date of egg retrieval. For instance, if the ER was done 4 weeks ago, we consider that the date of ovulation and add 2 weeks, so the end result is 6 weeks gestation. Please note that 80% of patients will deliver within 2 weeks of their due date which is at 40 weeks. During the first obstetrical vaginal ultrasound examination, we evaluate the pregnancy by determining the number of sac or fetuses and the presence of heartbeat. A normal pregnancy will have a fetus with a beating heart that can be visualized on ultrasound as early as 6 weeks of gestation or 4 weeks after ER. Occasionally, it will take few more days for the heartbeat to appear. Therefore, if a heartbeat is not seen at 6 weeks, we will request a repeat examination 1 week later. If there still is no heartbeat at 7 week, the pregnancy is considered abnormal and all medications are discontinued. In the majority of cases, the patient would then miscarry spontaneously within the next 2 weeks. Occasionally a D&C would be necessary to evacuate the pregnancy.
A pregnancy that has a sac but no live fetus is called a Clinical pregnancy. There are instances where the ultrasound is performed and no pregnancy is seen. We will then immediately measure an hCG level to determine if it is an abnormal pregnancy that will eventually miscarry or it is a possible ectopic pregnancy outside the uterus. A pregnancy with no gestational sac but with the presence of hCG hormone in blood is considered a Chemical pregnancy. Most such pregnancies will end as a heavy period few days after the discontinuation of all the hormones.
If the 6 weeks ultrasound is normal, we will follow it up with another ultrasound at 8 weeks and a final ultrasound at 10 weeks.
If all is well, the patient is discharged to her Obstetrician for pregnancy care. All medications except for prenatal vitamins are discontinued at 10 weeks gestation.
Dr. Sahakian is Board Certified in both Obstetrics/Gynecology and Reproductive Endocrinology & Infertility and assumes teaching responsibilities at Department of Obstetrics & Gynecology at UCLA Hospitals.
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