Unlocking the Mystery of Estradiol Levels: A Guide to Their Role in TTC and IVF Success

For many couples, in vitro fertilization (IVF) can be a highly effective and efficient treatment approach that shortens the time it takes to GET pregnant and increases the chance of being able to STAY pregnant. IVF is a complex process that involves multiple steps and precise hormonal regulation. We are both stimulating the ovary to grow follicles and mature the eggs they contain, while also suppressing the body’s natural tendency to ovulate eggs once they become mature. We are essentially trapping the eggs in the ovary while they mature so that we can extract them all at once, at time of egg retrieval. Estrogen (formally referred to as ‘estradiol’ in our field) is the hormone produced by growing follicles and their maturing eggs – we measure these levels in blood work to monitor response to treatment. In this blog post, we will delve into the world of estradiol/estrogen levels, their importance in IVF, and how monitoring them can contribute to a successful outcome.

What is Estradiol?

Estradiol is the primary form of estrogen, a female sex hormone responsible for regulating the menstrual cycle, promoting the growth of the uterine lining (endometrium), and preparing the body for pregnancy. Estradiol levels vary throughout the menstrual cycle, with the highest levels occurring during the follicular phase, just before ovulation. In the context of IVF, estradiol plays a crucial role in monitoring follicular development, endometrial receptivity, and embryo implantation.

Estradiol Levels and IVF:

Ovarian Stimulation and Follicular Development

The first step of IVF treatment involves ovarian stimulation, during which fertility medications are administered to encourage the growth of multiple follicles containing eggs. Estradiol levels are closely monitored throughout this phase, as they provide valuable information on follicular development and egg maturity.

Rising estradiol levels are a sign that the follicles are developing well and producing mature eggs. However, estradiol levels that are not rising (or rising minimally, or even falling) indicate poor/low response to stimulation and estrogen levels that rise really rapidly and to high levels (over 4000/5000 pg/ml by the time of trigger shot) signify over response and potential risk of ovarian hyperstimulation syndrome (OHSS), where the ovaries get enlarged and there is fluid retention and accumulation in the abdomen and pelvis. We can roughly estimate how many mature eggs a patient can expect at time of egg retrieval based on the size of follicles at time of trigger shot (any follicle over 14-15mm diameter has a good shot at yielding a mature egg at retrieval, even better if 17-18mm or larger) and estradiol levels (every follicle containing a mature egg is thought to produce ~200-300 pg/ml of estrogen in the blood work – ie. if you have levels of 1200-1500 pg/ml on day of trigger, I would guess we might get anywhere from 4-7 mature eggs). Estradiol levels can also differ from one person to the next and should not be used as absolute predictors of the number of eggs one will get – but they can be used as a rough guide to temper egg-retrieval-day-expectations for the clinic/embryology lab and the patient.

Endometrial Receptivity for Embryo Transfer and Implantation

To facilitate embryo implantation, the lining of the uterus (endometrium) must be thick enough, receptive and ready to support the developing embryo. Estradiol is essential for endometrial growth, thickening and proliferation. During IVF, estradiol levels are used as an indicator of endometrial receptivity.

In general, the endometrium should attain at least a 6-7 mm thickness to adequately support an implanting embryo. This type of lining can usually be achieved with estradiol levels 200-300 pg/ml as this is what you would expect when maturing a single follicle (which is what happens in a regular unmedicated/unstimulated cycle). Sometimes patients need higher doses of estrogen to achieve adequate lining thickness – and this may be reflected in higher estradiol levels in the blood work. It is important to note that there is no specific estradiol cut off associated with a ‘good’ lining for embryo transfer. But if doing a fresh transfer a week after egg retrieval, excessively high levels (a high ovarian response) can be associated with poor endometrial receptivity, reducing the chances of successful implantation. This is often due to unnatural or supra-physiologic estrogen levels AND the other hormones and factors secreted from ovaries with a robust response to stimulation (progesterone).

Maintaining Early Pregnancy

Once the embryo implants in the uterus, it begins to produce human chorionic gonadotropin (hCG), the hormone responsible for maintaining the corpus luteum (the follicle which released a mature egg) which, in turn, continue to produce progesterone and estradiol. In early pregnancy, adequate amounts of estradiol and especially progesterone are vital to stabilize the endometrial lining and support the developing embryo and maintain a healthy pregnancy.

Progesterone levels are routinely monitored during early pregnancy to ensure proper hormonal balance and to identify any potential issues that may require intervention.

Estradiol levels can vary from one person to the next and there is no distinct ‘cut-off’ to determine whether a pregnancy is healthy or not. Progesterone levels are more critical in this regard- it is ideal to have levels ~10 ng/ml or greater in an unassisted pregnancy conceived from a single ovulated follicle (or from a clomid/letrozole stimulated cycle) and the goal/threshold for progesterone levels will likely be higher in embryo transfer cycles (especially if a medicated cycle where there is no corpus luteum to produce progesterone on its own). I use a minimum threshold of 18 ng/ml progesterone for embryo transfer cycles (if the levels are below this, I will increase the dose of progesterone supplementation to err on the side of caution and ensure we are adequately supporting the pregnancy before the placenta takes over progesterone and estrogen production at 7-10 weeks of pregnancy).

Optimal Estradiol Levels during an IVF Cycle

It’s important to note that estradiol levels can vary significantly between individuals, and the “optimal” values may differ depending on various factors, such as age, ovarian reserve, and the specific treatment protocol. However, I can provide you with a general guideline for estradiol levels during an IVF cycle. Estrogen levels often begin rising BEFORE we see growing follicles – it is the first sign that someone is responding to the medications. Some patients may take longer to begin responding – and there is no one size fits all expectation when it comes to this. Keep in mind that these values are approximate and should be used for informational purposes only. Consult with your fertility specialist for personalized advice.

Day of IVF Stimulation Meds (if starting on day 3 of menstrual cycle or after stopping birth control)	Typical Estradiol Values (pg/mL)
1	25 -75
2	50 – 100
3	100 – 200
4	200 – 400
5	400 – 800
6	800 – 1200
7	1000 – 1600
8	1200 – 2000
9	1600 – 2400
10	2000 – 3000
11	2400 – 4000

The Importance of Individualized Care:

Given the complex relationship between estradiol levels and IVF outcomes, it is essential to recognize that each patient is unique, and treatment protocols should be tailored accordingly. Factors such as age, ovarian reserve, and medical history can significantly influence hormonal responses and IVF success rates.

As a reproductive endocrinologist and infertility specialist, I work closely with my patients to create individualized treatment plans that optimize their chances of success. By monitoring estradiol levels and adjusting treatment protocols as needed, we can ensure ovarian/endometrial stimulation is effective, safe, and giving a patient the best chance of a successful treatment outcome.