Why You Need to Take Estrogen During Your IVF Cycle

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If you're about to undergo in vitro fertilization (IVF), your doctor likely prescribed estrogen to help you conceive. You might be surprised, especially if you've been told your body makes too much estrogen, but this is a common practice.

Read on to learn more about the benefits of estrogen treatment, the possible side effects, and why doctors recommend women take Estrace (estradiol) during IVF.

Side Effects of Taking Estrogen During IVF Cycle
Verywell / Brianna Gilmartin

What Is Estrogen?

Hormones are the body's chemical messengers. They help control how cells and organs work. Your ovaries make most of your estrogen from fat molecules.

Estrogen kicks off puberty by making your breasts and pubic and underarm hair grow. It also controls your periods and helps with other body functions. For example, estrogen helps keep your mind and bones strong, regulates cholesterol levels, and prevents heart disease.

Your body makes three types of estrogen:

  • Estradiol: This type is active from puberty to menopause. It's the strongest of the three. It controls your menstrual cycle.
  • Estriol: Your body starts producing this type around the 8th week of pregnancy. It helps your uterus grow and prepares your body for childbirth.
  • Estrone: This type is a diluted form of estrogen. It's the only kind you make after menopause.

How IVF Works

In vitro fertilization (IVF) is a procedure that helps people with infertility conceive. Healthcare providers collect mature eggs from your ovaries. They fertilize them with sperm. Then the fertilized eggs are transplanted back into your uterus five to six days later.

You can use your eggs and partner's sperm. Or you can use eggs, sperm, or embryos (fresh or frozen) from a donor. A landmark IVF study published in 2003 found there's a window of time when a woman's uterus is receptive to a fertilized egg. Estrogen helps make this happen.

Estrogen levels naturally rise and fall during a woman's menstrual cycle. Some of the drugs women take for IVF decrease estrogen levels. The researchers suggested using estrogen to prime the lining of the uterus before IVF.

Estrogen Before IVF

A review published in 2015 in Medicine analyzed 11 studies. It found that taking estrogen and progesterone improved the chances of clinical pregnancy compared to taking just progesterone.

Clinical pregnancy means the women's pregnancy hormones rose, and doctors confirmed a heartbeat on an ultrasound. Other outcomes, including miscarriage (pregnancy loss) rates, were the same.

Another analysis of 19 studies published in 2020 also found that taking both hormones improves early pregnancy chances.

Doctors now routinely prescribe estrogen days before women undergo IVF. This helps thicken the lining of the uterus and prepare it for pregnancy. Researchers say this process is essential if you're using frozen embryos.

What to Expect When Taking Estrace

Estrace (estradiol) is the most common estrogen prescription. The doses doctors use can vary.

Most doctors begin by prescribing 2 milligrams (mg) once or twice a day on the first day of a woman's cycle. They slowly increase levels as patients approach ovulation. This is when your ovary releases an egg.

Your doctor may tell you to insert the pill into your vagina instead of swallowing it. It's the same pill, just a different delivery method. Studies show both ways work about the same.

If you take estrogen vaginally, you may notice a blue-green discharge. This is harmless. Once you insert the pill, you should lie down for at least a half-hour so it doesn't fall out.

There are also estrogen patches that you stick onto your belly. Your body absorbs the estrogen through your skin.

Side Effects

Using estradiol for more than a year can increase your risk of blood clots, stroke, or heart attack. Estradiol has also been shown to increase the risk of cancer of the breast, uterus, or ovaries.

However, these risks are lower if low doses are used for less than a year. Taking estrogen in combination with progesterone also helps offset the risks. Other possible side effects may include:

  • Light vaginal bleeding 
  • Upset stomach
  • Nausea, vomiting
  • Vaginal discharge
  • Vaginal itching
  • Rapid weight gain
  • Bloating
  • Swelling of the hands, feet, ankles
  • Headaches
  • Breast tenderness or pain
  • Skin irritation
  • Rash

Do not stop taking estradiol before consulting your healthcare provider. This could affect your IVF cycle.

Summary

Doctors prescribe estrogen supplements to women undergoing IVF to help thicken the lining of the uterus. This increases the chances a fertilized egg will implant in the uterus. Estrogen supplements come in pills that you swallow or insert into your vagina, or belly patches.

Most short-term side effects range from light vaginal bleeding to skin rash. If you take an estrogen-based medication and have symptoms that concern you, speak to your healthcare provider or pharmacist.

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6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Hormone Health Network. What is estrogen? Last updated August 2018.

  2. Ma W, Song H, Das SK, Paria BC, Dey SK. Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proc Natl Acad Sci U S A. 2003;100(5):2963-2968. doi: 10.1073/pnas.0530162100

  3. Zhang XM, Lv F, Wang P, et al. Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysisMedicine (Baltimore). 2015;94(8):e459. doi:10.1097/MD.0000000000000459

  4. Hao J, Xu B, Wang Y, Li Y, Zhao J. Impact of estradiol supplementation during luteal phase support on the in vitro fertilization clinical outcome: systematic review and meta-analysis. Archives of Obstetrics and Gynaecology. 2020;1(1).

  5. Liao X, Li Z, Dong X, Zhang H. Comparison between oral and vaginal estrogen usage in inadequate endometrial patients for frozen-thawed blastocysts transfer. Int J Clin Exp Pathol. 2014;7(10):6992-6997.

  6. U.S. National Library of Medicine. DailyMed. Label: Estrace—estradiol tablet. Updated May 31, 2018.

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