IVF 101:

There are several types of medications used during the IVF process. Gonadotropins are two hormones produced in the pituitary gland (LH and FSH) and one that is usually produced by the cells of the placenta during pregnancy (human chorionic gonadotropin or hCG). Gonadotropin medications are used to stimulate the ovaries to produce multiple egg-containing follicles during an IVF cycle. In addition to gonadotropins, the IVF cycle also involves synthetic forms of gonadotropin-releasing hormone (GnRH). This hormone is naturally produced in the brain’s pituitary gland and stimulates the ovaries. There are GnRH agonists which work by first stimulating the pituitary gland to release any stored gonadotropins (LH and FSH) and then, over the course of about 7–10 days, suppress the production of any new gonadotropins. There are also GnRH antagonists that help prevent premature ovulation, but they do not produce the initial surge of LH and FSH that agonists do. The IVF cycle may also involve progesterone in the luteal phase. Depending on your protocol, pre-cycle medication such as estrogen or testosterone may be prescribed.

The medications used in IVF may come in different forms but are usually self-administered injections that are inserted under the skin of the abdomen or thigh. Self-administering injectable medications can seem daunting for many people, but there are simple techniques and strategies to make the process as easy and painless as possible. Preparing the medications and syringes ahead of time and creating a comfortable environment in which to administer the medications can help ease any anxiety about the process.

During the IVF cycle, the patient will be required to come into the fertility clinic for regular monitoring appointments. Monitoring appointments are important to closely observe the development of follicles and the hormonal response of the ovaries. During these appointments, the patient will usually receive blood tests and a transvaginal ultrasound. The results of these tests can help the fertility specialist monitor your response to the medications and can also help them make decisions about the timing of the egg retrieval procedure. If necessary, the results of this test can help the provider know if they should adjust the medication dosage or any other part of the protocol. The frequency of monitoring appointments during IVF can vary but in most cases, patients will be asked to come in every 1-3 days, depending on where they are in the IVF cycle.

Patients going into an egg retrieval are given intravenous (IV) sedation to prevent discomfort during the procedure and is typically administered by an anesthesiologist. In preparation for the retrieval, patients are asked not to eat or drink anything after midnight the night before the procedure. The sedation used during egg retrieval will put the patient to sleep for the duration of the procedure, and the anesthesiologist will monitor vital signs such as blood pressure and heart rate. Once the egg retrieval is complete, the anesthesiologist will gradually lower the amount of medication administered through the IV, and the patient will wake up shortly after. While they may initially feel groggy, the effects of the sedation should wear off shortly, although patients are advised not to drive or perform demanding tasks the day of the procedure. Most patients can resume normal activity the next day but should avoid heavy lifting and high impact exercise for two weeks.

A sperm collection may also be required on the day of the egg retrieval during the IVF process. This sample collection is performed in the same way as it is for semen analysis, typically in a private room in the fertility clinic. Typically, men are instructed to avoid sexual activity or any ejaculation for at least two days but no more than five days before providing the semen sample. The clinic provides a sterile, nontoxic plastic jar to collect the semen, and will provide instructions on how to transport the sample to the medical team. 

To prepare the sperm in the semen sample to fertilize the retrieved eggs, the medical team will filter the semen to select the sperm with the best morphology and motility. Once those sperm are filtered from the sample, they are washed and placed in a solution. In natural insemination, these sperm are then added to the petri dish containing one or more eggs. The embryologist will monitor the culture medium the next day and transfer any fertilized embryos to a different medium to support growth.

In some situations, fertility providers may also recommend assisted hatching, a procedure that takes place after fertilization. An embryo typically “hatches” from its membrane (known as the zona pellucida) about five or six days after fertilization, which allows it to implant into the uterine lining. Older women or those who have had previous unsuccessful IVF cycles may be advised to go through assisted hatching, which involves making holes in the embryo’s zona pellucida before transfer, which can help the embryo implant correctly. This method is also often recommended for eggs or embryos that have previously been frozen, since this can harden the outer membrane. 

Preimplantation genetic testing (PGT) is another procedure that fertility experts may recommend in certain situations. This type of testing screens for specific genetic diseases or an abnormal number of chromosomes known as "aneuploidy,” and is often performed after five to six days of development. To perform PGT, a few cells from the outer trophectoderm, which forms the placenta — not the embryo which is the inner cell mass or ICUM — are removed in the lab and tested.

Based on these criteria, the embryos are graded on a scale. The grading system may vary between fertility clinics, but the most common systems involve numerical values (e.g. 1 to 5, with 1 being the worst and 5 being the best) and alphabetical (e.g. A, B, C, etc. with A being the best). Embryos are typically graded on day 3 and again on days 5, 6, and possibly 7 when they have developed into blastocysts (a cluster of dividing cells that usually forms on day 5), depending on their progress.

For individuals or couples who choose to do genetic testing, this is also the time when the embryos are biopsied and the samples are sent for PGT. There are several types of PGT sometimes specified as preimplantation genetic testing for aneuploidy (PGT-A) and preimplantation genetic testing for monogenic disorders (PGT-M). This type of testing can be used to screen for specific genetic conditions or chromosomal abnormalities in the embryos before they are transferred and implanted into the uterus. 

While PGT-M is used to detect specific genetic disorders or single gene mutations in embryos, PGT-A is used to analyze the chromosomal makeup of embryos, which can help identify chromosomal abnormalities, like aneuploidies (an abnormal number of chromosomes). PGT-M is typically recommended for individuals who are known carriers of genetic disorders or who have a family history of genetic conditions. The testing involves removing a small number of cells from the embryo when it reaches the blastocyst stage and testing for the presence of a genetic mutation. When PGT-A is used, fertility specialists are looking for aneuploidies, which can lead to implantation failure, miscarriages, or certain genetic conditions like Down syndrome. This type of PGT is often recommended for older women or those who have experienced recurrent pregnancy loss.

Patients who have an FET often take medications like birth control pills or injectable leuprolide (Lupron) prior to the cycle start in order to reduce the activity of the ovaries. After the ovaries have been suppressed, the fertility provider will likely prescribe estrogen in the form of a pill, injection, or patch to help prepare the uterine lining to receive the embryo. Estradiol levels may be monitored through blood tests and the lining of the uterus may be measured via ultrasound for several weeks until the uterine lining is ready for implantation. At this point, the provider will likely prescribe progesterone as a pill, gel, or injection. While every case is different, many patients will continue taking estrogen and progesterone even if they become pregnant and use these medications until they are at least 10 weeks into pregnancy.

The embryo transfer procedure is typically simple and rarely requires sedation or anesthesia. During the procedure, a long, flexible tube called a catheter is passed through the cervix into the uterus. Inside the catheter is the embryo being transferred along with a small amount of fluid. The contents of the catheter is then released into the uterus and an abdominal ultrasound is performed simultaneously to make sure the embryo is properly placed. While there may be some instances that require multiple embryos to be transferred at once, single embryo transfer (SET) is the single most predictive indicator of a singleton IVF pregnancy and subsequent successful live birth. It is an important clinical protocol used to avoid multiple gestation pregnancies, which are associated with higher medical costs and poorer health outcomes for mothers and infants. In 2023, Carrot published the results of an internal study demonstrating the highest reported SET rate of fertility benefits vendors as well as an IVF pregnancy rate greatly exceeding national averages.

While frozen embryos may be stored and implanted years after they are created, fresh embryos are transferred either 3 or 5 days after they are created. Day 3 embryos are known “cleavage embryos” which refers to the cells in the embryo “cleaving” or dividing. Day 5-6 embryos are known as “blastocysts” and are more developed. A fertility provider will determine whether to transfer a cleavage embryo or blastocyst depending on the patient and their specific circumstances. 

Same-sex female couples may choose to do a specific form of IVF known as reciprocal IVF. In reciprocal IVF, one partner contributes eggs to form an embryo and one partner receives the embryo and carries the pregnancy. This type of IVF is sometimes also referred to as partner-assisted reproduction, co-maternity, co-motherhood, co-parenthood, co-IVF, or reception of oocytes from partner (ROPA). Couples considering the option will want to know the various steps involved in the process, including deciding which partner provides the genetic material and which carries the pregnancy, choosing donor sperm, synchronizing menstrual cycle, and more. There are also legal considerations of reciprocal IVF that are unique to the process and important to consider.

It will take about 12-14 days for a pregnancy test to confirm whether the embryo transfer resulted in a pregnancy. The fertility provider will perform a blood test at this time and if the patient is pregnant, they are monitored by the fertility clinic for a few weeks in early pregnancy and then referred to an OBGYN for prenatal care (usually week 10). If the patient is not pregnant two weeks after the embryo transfer, they will discontinue medications will get a period within a week. If another IVF cycle or implantation is being considered, the patient will work with the fertility provider to discuss next steps.