During the first half of a menstrual cycle, estrogen helps thicken the endometrium to make it optimal for embryo implantation. After ovulation, progesterone changes the texture of this plush lining to prepare it for the implanting embryo.
Your fertility doctor will prescribe a specific medication regimen for you to follow before your FET cycle. This includes avoiding sexual intercourse and taking a folic acid supplement.
Estrogen
During a normal menstrual cycle, estrogen from the ovaries helps to prepare the uterus for embryo implantation. This preparation is necessary to ensure that the endometrial lining has a thickness of 7mm or greater and has a trilaminar pattern on ultrasound, which is a prerequisite for implantation and pregnancy. During an IVF treatment cycle, doctors use medications to take the place of the hormones that would normally be produced during the natural menstrual cycle and help to prepare the endometrium for embryo implantation.
The synthesis of estrogen in the ovary is stimulated by Luteinizing Hormone (LH) from the anterior pituitary gland. Estrogen is synthesized in the granulosa cells of the follicle, and the primary molecules that are converted to estrone or estradiol are cholesterol and androstenedione. These compounds then enter the bloodstream and travel to extragonadal tissues, where they can be converted to more estrogens. The majority of estrogens that are absorbed from the bloodstream act as an anabolic steroid in the body, promoting growth and development of the uterus and other female organs.
When taken in excess, however, the effects of estrogen can be harmful to the fetus. High levels of estrogen are linked to a higher incidence of preeclampsia, low birth weight, and small for gestational age babies in newborns. In IVF, excessive estrogen also can lead to a higher rate of early miscarriage and an increase in the risk of having a chromosomally abnormal embryo that cannot implant.
Researchers have found that the duration of estrogen exposure is an important factor in successful implantation and pregnancy outcomes. A short time exposure of 5-10 days to supraphysiological levels of estrogen can stimulate endometrial proliferation and induction of progesterone receptors, which are necessary for embryo implantation [Citation35].
In addition, the timing of the onset of progesterone is critical to the success of a frozen embryo transfer (FET) cycle. This is because the synchronization of endometrial and embryonic development needs to occur within a window of opportunity that is not guaranteed by the fixed duration of the exposure to estrogen.
Progesterone
Progesterone is the key hormone for uterine receptivity and embryo implantation. It thickens the lining of the uterus (called the endometrium) to help an implanted fertilized egg adhere and grow. Progesterone also suppresses uterine contractions and encourages the growth of milk-producing glands during pregnancy.
Like estrogen, progesterone is made in the ovaries and adrenal glands. It levels rise during a menstrual cycle and are lower after menopause, but they continue to play an important role in reproduction. Unlike estrogen, progesterone is a “progestogen” and doesn’t act as an androgen.
Women who have low progesterone can have irregular menstrual cycles, and their uterus is less receptive to pregnancy. This can decrease fertility, lead to miscarriage and affect overall health.
For IVF patients, it’s critical to have adequate progesterone levels for a successful embryo transfer cycle. During the luteal phase (LP), which begins after ovulation, a woman’s progesterone levels begin to go up. The LP is the time when the uterus is most receptive to an implanted fertilized egg.
If you’re wondering what happens 5 days after embryo transfer, this is typically the time when the embryo begins to implant into the uterine lining, marking a crucial step in the fertility journey. The LP is a crucial phase for any fertility treatment because it’s when an embryo can implant and survive. During IVF, the LP is shortened by using ovulation induction medications such as letrozole or human chorionic gonadotropin (hCG). This means you can have a more predictable timeline of your fertility treatment and minimize your stress and monitoring.
Fresh transfer is when an embryo is transferred to your uterus after it’s been created in the laboratory. The day of a fresh transfer depends on the date of ovulation and the developmental stage of the embryos, with cleavage-stage embryos being transferred three days after ovulation and blastocyst-stage transfers happening five days after.
If you choose a fresh cycle, you’ll be given medications such as Follicle Stimulating Hormone (FSH) and Human Chorionic Gonadotropin (hCG). The combination of these two drugs stimulates multiple follicles to mature eggs. Once a good number of eggs are created, you’ll be told when to return for a transfer.
Human Chorionic Gonadotropin (hCG)
hCG is a molecule that has multiple biological functions and binds to the hCG/LH receptor. hCG promotes progesterone production by corpus luteal cells of the ovary; promotes angiogenesis in the uterine vasculature to ensure sufficient blood supply for the invading placenta during pregnancy; promotes the fusion of cytotrophoblast cells and their differentiation to make syncytiotrophoblast cells, which form the villous aspect of the placenta; acts on the myometrium to suppress any contractions during pregnancy and to cause the lining of the uterus to thicken; signals the endometrium that implantation is about to occur; induces a chemical change in the mother’s brain that causes hyperemesis gravidarum; and also apparently has a role in promoting growth of fetal organs during pregnancy.
The hCG/LH receptor is present on the trophoblastic cells of the uterus, the decidua and myometrium. It binds to intact hCG, LH and its free subunits (hCGa and hCGb). Hyperglycosylated hCG is made by root cytotrophoblast cells or extravillous cytotrophoblast cells as pregnancy progresses. Laboratory studies show that antibody to hyperglycosylated hCG (antibody B152) blocks growth of cytotrophoblast cell lines in vitro and inhibits invasion by choriocarcinoma cells during implantation of pregnancy.
After embryo transfer, you will have a blood test performed to determine if you are pregnant. If you are not pregnant, we will schedule an appointment to test again after two weeks to get a more accurate reading.
During the transfer procedure, a long, thin catheter containing the agreed upon number of embryos is inserted into the uterus through the cervix. This is performed in a doctor’s office, and an ultrasound is simultaneously performed to ensure the correct placement of the embryo or embryos.
After the transfer, it is important to limit your physical activity for a few days following the procedure to avoid uterine inflammation or bleeding. If you have any unusual pain, cramping or bleeding, please call your fertility clinic. You will likely be referred to an obstetrician or other pregnancy specialist for further prenatal care. While many fresh embryo transfer cycles have success rates similar to those of frozen embryo transfers, there is some evidence that a frozen embryo transfer may be even more successful than a fresh one, due to factors such as fewer residual retrieval hormones and physician technique and knowledge.
Donor Eggs
If you decide to donate your eggs, it’s important to find a program that is experienced and understands the psychological and physical stress of egg donation. Make sure to discuss all of your questions and concerns with the donor coordinator and doctor.
For fresh egg donations, you’ll receive injections to help your follicles grow large enough for an expert embryologist to harvest. Your doctor will tell you when the follicles are ready for retrieval, and this procedure usually takes half an hour. You’ll be sedated or given a general anesthetic to make this painless.
After your follicles are removed, your egg cells will be combined with the sperm of a male or donated sperm in the laboratory to form embryos. Depending on your situation, one or more of these embryos may be transferred to the uterus of the intended parent or gestational carrier. The remaining embryos will be frozen for future use.
It’s possible that you could become pregnant from this cycle, so you should abstain from unprotected intercourse and use effective barrier contraception during the treatment period. This is especially important if you decide to use a frozen egg.
If you’re using a donor egg, the clinic may have additional requirements. All donors are required to undergo extensive testing and a physical exam. They’re also required to provide a detailed medical history and genetic test. The tests screen for significant medical problems, as well as genetic markers for certain diseases. They also check for blood type, Rh factor, and antibodies to HIV (AIDS), hepatitis, syphilis, chlamydia, and gonorrhea.
You should also ask about the program’s policy on withdrawing consent to donate. Some programs will not allow you to withdraw before you undergo the process. You should also find out if the program knows who will be receiving your eggs and the resulting embryos. If you’re not comfortable with this, you can ask to be added to a pool of known donors or to donate your eggs to an anonymous recipient. Alternatively, you can ask to have your eggs used in an artificial insemination (AIV) procedure with an unused fertilized egg from another couple’s IVF treatments.