IVF Medications Explained – A Complete Guide for Surrogates
Gestational carriers are women who carry a pregnancy to term for another person or couple. In order to initiate this type of pregnancy, an embryo that was created through in vitro fertilization (IVF) is transferred into the gestational carrier’s uterus. The hope is that the embryo implants into her uterine lining (endometrium) to initiate a healthy pregnancy.
In short, IVF consists of retrieving eggs from a woman’s ovaries and fertilizing them with sperm in a petri dish. Any resulting embryos that develop properly can be transferred into a woman’s uterus to initiate a pregnancy.
Types of IVF Medications
Women who undergo an egg retrieval procedure must administer prescribed medications that stimulate the follicles (fluid-filled sacs that contain eggs) in her ovaries so multiple eggs are available for IVF and control when she ovulates. These medications are often administered for 8-12 days prior to her egg retrieval procedure. However, gestational carriers are not required to administer these medications since they do not undergo egg retrieval procedures.
If a woman is undergoing an (fresh or frozen) embryo transfer, she may need to administer a separate regimen of medications that prepare her uterine lining for embryo implantation. Gestational carriers are often required to administer these medications prior to undergoing an embryo transfer.
What Happens During a Normal Menstrual Cycle?
During a normal menstrual cycle, the ovaries release increasing amounts of the hormone estradiol (E2) prior to ovulation. E2 travels to the uterus to thicken the endometrium with nutrients and blood, which helps to create an optimal environment for embryo implantation and development once it enters the uterus.
Once ovulation occurs, the egg:
- Is expelled from its follicle in the ovary (the follicle then becomes known as the corpus luteum).
- Enters the fallopian tube, where insemination can occur if sperm is present.
- Travels down the fallopian tube for a few days before entering the uterus.
The corpus luteum continues to produce the hormones E2 and progesterone (P4). Like E2, P4 travels to the uterus to thicken the endometrium. If implantation occurs, E2 and P4 continue to be produced to maintain the pregnancy until about 12 weeks gestation when the placenta takes over hormone production. If implantation does not occur, the corpus luteum degenerates, E2 and P4 are no longer produced, the endometrium breaks down, and the woman gets her period.
Unmedicated (Natural) Embryo Transfers
Some women are not required to administer medications prior to an embryo transfer. These are known as natural cycles and rely on the woman’s own hormones to thicken the uterine lining and maintain a pregnancy. Other times, only some medications are administered (for example, a trigger shot to ensure that ovulation occurs or progesterone to maintain a pregnancy). The woman is carefully monitored throughout her cycle to determine if ovulation occurred and her endometrium is thick enough for embryo implantation to occur following the transfer.
Medicated (Artificial) Embryo Transfers
Many women undergo medicated (artificial) embryo transfer cycles, during which medications are administered throughout the menstrual cycle to optimize endometrial receptivity when an embryo transfer occurs. Medicated cycles are usually required when a woman does not ovulate on her own, experiences abnormal menstrual cycles, has hormonal imbalances, or has a history of poor endometrial development. Further, these cycles can control when the embryo transfer occurs and require less monitoring appointments.
During the later part of the menstrual cycle prior to an FET cycle, a woman may administer daily intramuscular injections of a GnRH agonist such as Leuprolide Acetate (Lupron) for ~7 days or an oral birth control pill (OCP) for 10+ days. These medications prevent egg maturation and ovulation from occurring during the following (FET) cycle to better control the timing of the FET. Lupron is injected into the muscular areas of the thigh, gluteal area, or upper arm to provide quick absorption of the medication into the bloodstream.
At the start of a medicated cycle (when a woman gets her period), she will stop taking or decrease the dosage of the GnRH agonist (if applicable) and schedule a baseline appointment at her IVF clinic (usually 2-4 days after her period begins). If she is cleared to move forward with her cycle, she will begin to administer estrogen, which is available as a(n):
- Oral pill (ex. Estrace)
- Transdermal patch (ex. Dotti transdermal patch)
- Transdermal gel (ex. Oestrogel)
- Vaginal tablet (uncommon)
- Subcutaneous or intramuscular injection (uncommon)
Administering these medications mimics E2 production by the ovaries, causing the endometrium to begin thickening. It also prevents egg maturation and ovulation from occurring. There do not appear to be significant differences in success rates when one method is used over another, so most clinics prescribe estrogen pills or patches for convenience (source: A comparison of the effects of three different estrogen used for endometrium preparation on the outcome of day 5 frozen embryo transfer cycle – PMC (nih.gov)). However, oral estrogen is broken down by the liver before it enter the bloodstream, so some clinics now prefer to use transdermal patches to bypass the liver (source: Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen | Scientific Reports (nature.com)). Talk with your doctor about the best option for you.
After about 1.5-2 weeks (timing varies between clinics), the woman will return to her IVF clinic for more monitoring. An ultrasound will be used to determine if her endometrium is developing properly (generally ≥7mm in thickness and trilaminar in appearance). If it is not, additional medications can be administered or the cycle may be canceled. If it is developing properly, the woman will be instructed to begin taking progesterone on a specific day. Progesterone is available as a(n):
- Intramuscular injection (called progesterone in oil, or PIO)
- Vaginal tablet or suppository (ex. Endometrin)
- Vaginal gel (ex. Crinone)
- Oral pill (uncommon and less effective since most is absorbed by liver before entering bloodstream)
Intramuscular progesterone injections (usually into the buttocks) are currently the preferred method of administration because progesterone is absorbed slowly, so there are higher levels of it in the blood for a longer period following injections versus the other methods. However, some studies have found comparable ongoing and clinical pregnancy rates when suppositories or gels are used in place of injections (sources: A meta-analysis of the route of administration of luteal phase support in assisted reproductive technology: vaginal versus intramuscular progesterone (sciencedirectassets.com) and Retrospective Review of Reproductive Outcomes Comparing Vaginal Progesterone to Intramuscular Progesterone as Luteal Support in Frozen Embryo Transfer Cycles – Journal of Obstetrics and Gynaecology Canada (jogc.com)), though more studies are needed. Typically, PIO injections are administered in addition to supplemental vaginal gels or suppositories.
Note: Intramuscular PIO often contains sesame oil. If you are allergic to sesame oil or are having adverse reactions to PIO with sesame oil, please talk with your doctor about using a PIO with an alternative oil, such as ethyl oleate, cottonseed oil, or olive oil.
Exogenous progesterone mimics the P4 produced by the corpus luteum, which helps to thicken the uterine lining and maintain a pregnancy if one occurs. Most women continue to administer oral estrogen throughout this time, as well.
Unless a day 3 embryo is being transferred, the embryo transfer procedure will be scheduled on the sixth day of progesterone administration. Most often, embryo transfers occur on days 19-22 of a menstrual cycle when the endometrium is most receptive, though the timing can vary.
Typically, administration of both estrogen and progesterone is continued until around 8-12 weeks gestation if a pregnancy is confirmed. At this point, the placenta should begin to take over estrogen and progesterone production to maintain the pregnancy. Each clinic has its own protocol, so your physician will instruct you when to stop administering these medications.
A Note About Antibiotics
Whether you are undergoing a natural or medicated IVF cycle, your doctor may prescribe an antibiotic (such as a Doxycycline Hyclate oral pill) around the time of your embryo transfer (usually for 4-7 days). Antibiotics may help reduce the chance of failed embryo implantation due to the presence of abnormal bacteria in the vagina, cervix, or uterus. They also help to mitigate the risk of acquiring an infection during the embryo transfer. Some clinics do not prescribe antibiotics due to limited data about their efficacy (source: Withholding antibiotics does not reduce clinical pregnancy outcomes of natural cycle frozen embryo transfers – Fertility and Sterility (fertstert.org)).
Side Effects of Embryo Transfer Medications
All of the medications that are administered during an embryo transfer cycle have side effects.
In general, many women experience injection site reactions, which can include localized irritation, pain, tenderness, bruising, redness, and swelling. These are caused by irritation to the skin and surrounding tissue from the needle and medication administration, which can trigger an immune response. Most injection site reactions are mild and resolve on their own, but they can sometimes be serious and result in infections, high fevers, or allergic reactions (source: Injection Side Effects and When to Seek Medical Help (verywellhealth.com)). Seek immediate medical attention if you believe that you are experiencing any of these serious conditions.
In addition, the following medications may cause the following side effects:
- Lupron Depot: hot flashes, night sweats, nausea and vomiting, fatigue, diarrhea or constipation, headaches, breast tenderness, decreased libido, vaginal dryness or bleeding, headaches, depression or anxiety, and dizziness (source: Lupron (Leuprolide Acetate Injection): Uses, Dosage, Side Effects, Interactions, Warning (rxlist.com))
- Birth control pills (OCPs): dizziness, headaches, nausea, stomach pain or bloating, and mood swings (source: Oral Contraceptive Pills (OCP): What You Should Know (verywellhealth.com))
- Estrogen: nausea/vomiting, vaginal discharge or bleeding, rash or skin irritation, headaches, patch site reactions, and breast tenderness (source: The Role of Estrace (Estradiol) in IVF (verywellhealth.com)
- Progesterone: vaginal itching/discomfort, dizziness, tiredness, nausea/vomiting, abominable cramping and bloating, and mood swings (source: Should I Expect Side Effects When Taking Progesterone for IVF? (cofertility.com))
- Doxycycline side effects: nausea/vomiting, yeast infections, diarrhea, headaches, hypertension, and abdominal pain (source: Doxycycline monohydrate: Side Effects, Interactions, Warnings and More. (msn.com))
Also always look out for signs of an allergic reaction to any medication, which may include a rash, hives, swelling, or difficulty breathing.
Are There Ways to Make IVF Injections Less Painful?
Many people are not comfortable with administering injections because they can be painful. Fortunately, there are some ways to reduce injection site pain, including:
- Apply a numbing cream (with your doctor’s approval) and/or ice pack to the area before the injection
- Apply a warm compress, heat pack, or ice pack to the injection site following the injection to relieve pain
- For PIO, warm the oil to room temperature to thin the oil out (do not warm beyond room temperature) and massage the oil into the muscle after the injection
- Rotate your injection site to reduce tenderness and bruising
- Ask someone to help administer your injections
- Consider using an auto-injector
- For intramuscular injections, try to relax the muscle prior to injection
Final Notes
It may seem like there are a lot of medications involved in the embryo transfer process, many of which are injections. Keep in mind that administering these injections is only temporary and try to focus on the big picture while administering them.