Treatment Decision

There is no single IVF protocol that is suitable for every patient. The medications used, their doses, the timing of treatment and even the type of cycle will depend on factors such as age, ovarian reserve, previous treatment response, menstrual regularity, underlying fertility diagnosis and whether your own eggs, donor eggs or previously frozen embryos are being used.

The terminology can initially seem confusing. You may hear terms such as agonist protocol, antagonist protocol, ovarian stimulation, down-regulation, trigger injection, endometrial preparation and luteal support. The purpose of this guide is to explain what these terms mean and, more importantly, why different protocols are used.

Broadly speaking, IVF treatment can be divided into two main types of cycles:

1. Ovarian stimulation cycles – used when a patient is undergoing IVF using her own eggs. Ovarian stimulation involves the use of hormonal medications to encourage the ovaries to develop multiple follicles simultaneously, rather than the single dominant follicle that typically develops during a natural menstrual cycle. The aim is to obtain several mature oocytes (eggs) at the time of egg retrieval, thereby increasing the number of oocytes available for fertilization and subsequent embryo development.

2. Endometrial preparation cycles – used when embryos are already available from a previous IVF cycle, or when donor eggs are being used. In these cycles, the objective is not to stimulate the ovaries to produce eggs, but to prepare the endometrium (the lining of the uterus) for embryo transfer. Hormonal medications are therefore used to promote appropriate development of the endometrial lining and create a suitable hormonal environment for embryo implantation and the early stages of pregnancy.

PART 1: IVF Using Your Own Oocytes (Ovarian stimulation cycles)

When IVF is performed using your own eggs, the first objective is to stimulate the ovaries so that multiple follicles develop simultaneously.

In a natural menstrual cycle, usually only one follicle becomes dominant and releases an egg. During IVF, injectable gonadotropins are used to support the development of several follicles so that multiple mature oocytes can potentially be collected at egg retrieval. The aim is not simply to produce the highest possible number of eggs. Rather, we aim for an appropriate and safe ovarian response that provides a useful number of mature oocytes while minimizing excessive stimulation and complications such as ovarian hyperstimulation syndrome (OHSS).

Two major approaches are commonly used to control the cycle: the GnRH agonist protocol and the GnRH antagonist protocol.

1. The GnRH Agonist Protocol

The GnRH agonist protocol aims to temporarily suppress the body’s natural hormonal signaling between the pituitary gland and the ovaries before ovarian stimulation begins. This helps prevent a premature LH surge and spontaneous ovulation, allowing follicular development to be controlled more precisely with stimulation medications. This is called down-regulation.

GnRH agonists, such as leuprolide acetate, work differently from antagonist medications. When first administered, they briefly stimulate the pituitary gland, but with continued use they cause it to temporarily This process is called down-regulation.

In simple terms, down-regulation places the ovaries into a temporary, reversible menopause-like resting state by reducing production of FSH and LH, the hormones that normally control ovarian activity. Once the ovaries have been adequately suppressed, we can introduce IVF stimulation medication and have greater control over follicular development and the timing of the treatment cycle. The effect is temporary, and normal ovarian hormone signaling returns after the medication is discontinued. The advantage is that the physician gains considerable control over endogenous pituitary hormone activity, reducing the likelihood of an unexpected LH surge during stimulation. There are two main agonist protocols that are in current use:

1.a. Long Agonist Protocol

This is the most popular GnRH agonist protocol. In a conventional long protocol, the GnRH agonist is usually introduced during the luteal phase of the cycle preceding ovarian stimulation, usually around day 21 of the menses. This is about one week before the onset of next menstruation. After next menstruation begins and adequate suppression is confirmed, ovarian stimulation is started.

The long GnRH agonist protocol may be particularly suitable for younger women with normal or good ovarian reserve, who are generally better able to tolerate the more profound pituitary suppression associated with this approach. It can provide excellent cycle control and follicular synchronization. However, it is not necessarily superior to GnRH antagonist protocols in this group, and the choice of protocol should be individualized according to ovarian reserve, expected ovarian response, previous treatment history, and the risk of ovarian hyperstimulation.

1.b. Agonist Flare / Microdose Flare Protocol

GnRH agonists initially produce a temporary release of endogenous FSH and LH before pituitary suppression develops. This is known as the flare effect. Certain protocols attempt to take advantage of this initial endogenous gonadotropin release by administering a low dose of GnRH agonist around the beginning of ovarian stimulation.

The microdose flare protocol may be considered in selected patients, particularly women who have demonstrated a suboptimal ovarian response in previous IVF cycles. However, it is not generally considered a preferred first-line stimulation protocol in contemporary IVF practice, as available evidence has not demonstrated a consistent advantage over other stimulation strategies in women with diminished ovarian reserve or previous poor response. Its use is therefore usually reserved for selected cases in which the treating physician believes that taking advantage of the initial GnRH agonist flare effect may be beneficial.

2. The GnRH Antagonist Protocol

The antagonist protocol is one of the most commonly used IVF stimulation protocols. Unlike the long agonist protocol, there is no prolonged suppression of the ovaries before treatment begins. Instead, ovarian stimulation usually starts within the first few days of the menstrual cycle.

Patients receive daily injections containing either follicle-stimulating hormone (FSH) alone or a combination of FSH and luteinizing hormone (LH) activity. As the follicles become larger, they produce increasing amounts of estradiol (estrogen). At a certain stage, your body may interpret this as a signal that the follicles are ready and produce a sudden increase in luteinizing hormone (LH), known as the LH surge. In a natural cycle, this LH surge is what ultimately leads to ovulation. During IVF, however, we need to prevent ovulation from occurring before we are ready to collect the eggs.

For this reason, a GnRH antagonist such as Cetrotide (cetrorelix) is introduced once the follicles have reached an appropriate stage of development. Cetrotide temporarily blocks the release of LH, preventing a premature LH surge and reducing the risk of ovulation before egg retrieval. Importantly, your follicles can continue growing while you are using Cetrotide.

The exact day on which Cetrotide is started is not necessarily the same for every patient. We may adjust its timing according to your follicle sizes, hormone levels, age and response during previous IVF cycles. This is one of the reasons ultrasound scans and hormone tests are performed during stimulation.

Modern guidelines generally favor GnRH antagonist protocols for the overall IVF population, because efficacy is comparable while treatment is shorter and the risk of OHSS is lower. The updated ESHRE guideline specifically recommends antagonist protocols over agonist protocols in the general IVF/ICSI population on the basis of comparable efficacy and greater safety.

3. The GnRH Agonist-Antagonist Conversion Protocol

The GnRH Agonist–Antagonist Conversion Protocol is a specialized ovarian stimulation approach originally developed in the early 2000s by Dr. Geoffrey Sher and colleagues for patients with a history of poor ovarian response or unsuccessful IVF treatment.

The protocol is designed to combine the follicular synchronization achieved with a GnRH agonist with the flexibility of a GnRH antagonist cycle. A GnRH agonist is usually started during the latter part of the menstrual cycle preceding IVF to temporarily suppress the pituitary gland and help synchronize the developing follicular cohort. Once menstruation begins, the agonist is discontinued, allowing some recovery from the deeper suppression, and ovarian stimulation is subsequently started. A GnRH antagonist is then used during the stimulation phase to maintain control over LH secretion and prevent premature ovulation.

The rationale is therefore to achieve good early follicular synchronization without maintaining profound agonist-induced pituitary suppression throughout ovarian stimulation. This may be useful in selected women with diminished ovarian reserve or a previous suboptimal response, in whom excessive suppression could potentially reduce ovarian responsiveness.

Because treatment begins during the cycle preceding ovarian stimulation, the complete protocol generally extends over approximately 3–4 weeks before egg retrieval, although the exact duration varies according to the specific version of the protocol and the patient’s response. It is a more specialized approach and has not been demonstrated to be universally superior to conventional antagonist protocols. We usually reserve this protocol for women in more advanced age brackets whose prior IVF cycles using alternative protocols failed to produce desired outcomes and a different strategy is thought to be potentially beneficial moving forward with another stimulation cycle.

Ovarian Stimulation Medication

Once stimulation begins, injectable gonadotropins are used to promote the development of multiple follicles. Gonadotropins are medications that include follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

FSH is the principal hormone responsible for stimulating the growth and development of the small antral follicles within the ovaries. In a natural menstrual cycle, rising FSH levels initially support the development of several follicles, but usually only one becomes dominant and ultimately releases a mature egg. During IVF, additional FSH is administered so that multiple follicles can continue developing simultaneously, increasing the number of mature oocytes (eggs) that may be available at the time of egg retrieval.

LH plays a complementary role in follicular development and oocyte maturation. It stimulates theca cells within the follicle to produce androgens, which are subsequently converted into estrogen by the granulosa cells under the influence of FSH. As follicles become more advanced, LH signaling also becomes increasingly relevant to their final stages of development and maturation. For this reason, LH activity may be included alongside FSH during ovarian stimulation, with the amount and timing individualized according to the patient’s age, ovarian reserve, hormonal profile, and response to treatment.

The balance between FSH and LH can be adjusted throughout the stimulation cycle depending on the individual patient. In some cases, we may begin treatment with FSH alone to focus primarily on early follicular growth and introduce LH activity later as the follicles develop. In other patients, we may use FSH together with a much smaller amount of LH from the beginning, providing some LH support while keeping FSH as the main driver of early follicular growth.

In younger women with a good ovarian reserve and adequate natural LH production, FSH alone is often sufficient at the beginning of stimulation, as the patient’s own LH can provide the additional hormonal support required for normal follicular development.

In other patients, we may choose to include a small amount of LH activity from the beginning. This may be considered when natural LH activity is relatively low, following significant pituitary suppression, in some older patients or women with reduced ovarian reserve, or when a previous IVF cycle has shown a suboptimal response to FSH alone. The amount of LH used does not necessarily need to be high; in selected patients, a smaller dose can provide additional LH activity while FSH remains the principal driver of follicular growth.

The decision is therefore individualized rather than based on age or ovarian reserve alone. Baseline hormone levels, ovarian reserve, previous stimulation history, and the response of the follicles during treatment all help determine the most appropriate balance between FSH and LH.

Preparations that contain recombinant FSH

GONAL-f: follitropin alfa
Puregon: follitropin beta; marketed as Follistim AQ in the U.S.
Rekovelle: follitropin delta
Bemfola: follitropin alfa biosimilar
Ovaleap: follitropin alfa biosimilar

FSH is particularly important for the recruitment and continued development of antral follicles, which is why FSH activity forms the foundation of most ovarian stimulation protocols. The dose required varies substantially between patients. Age, AMH, antral follicle count, body weight, previous response to stimulation and other clinical factors are considered when selecting the starting dose. The dose may subsequently be adjusted according to ultrasound findings and hormone results.

The different recombinant FSH preparations are generally comparable in their ability to stimulate follicular development, and there is no strong evidence that one routinely produces better pregnancy or live birth outcomes than the others. GONAL-f (follitropin alfa) and Puregon/Follistim (follitropin beta) have the longest clinical track record, while Rekovelle (follitropin delta) uses a different dosing system individualized according to factors such as AMH and body weight.

Bemfola and Ovaleap are biosimilar versions of follitropin alfa and have demonstrated comparable ovarian stimulation to GONAL-f in regulatory trials. They are often less expensive, although medication prices vary considerably between countries, pharmacies, and healthcare systems.

Preparations that include both FSH and LH activity

Preparations that include both FSH and LH activity provide additional LH support alongside FSH during ovarian stimulation. They are available either as recombinant preparations, such as Pergoveris (follitropin alfa + lutropin alfa), or as human menopausal gonadotropin (hMG) preparations, such as Menopur and Merional. hMG is derived from purified human urinary sources and provides FSH together with LH activity, much of which is contributed by human chorionic gonadotropin (hCG).

These medications may be used from the beginning of stimulation or introduced later in the cycle, depending on the patient’s baseline hormone levels, ovarian reserve, age, previous response to stimulation, and follicular development during treatment.

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In most of our protocols, especially in more advanced age brackets, FSH provides the predominant stimulation for follicular recruitment and growth, while a small amount of LH activity is included from the beginning of stimulation. This provides continuous LH support throughout follicular development without exposing the follicles to excessive LH activity early in the cycle. As the follicles mature, LH increasingly contributes to theca-cell androgen production, estradiol synthesis and the later stages of follicular and oocyte development, while final oocyte maturation is subsequently induced with the trigger injection.

Adjunct Medications

In addition to the standard gonadotropin medications used for ovarian stimulation, certain patients may benefit from adjunct treatments designed to improve follicular synchronization or modify the hormonal environment before or during stimulation. These medications are not required in every IVF cycle and are selected according to the patient’s ovarian reserve, previous treatment response and the characteristics of the individual cycle.

Letrozole

Letrozole is an aromatase inhibitor that temporarily reduces the conversion of androgens into estrogen. This causes a short-term reduction in circulating estrogen levels, which in turn can encourage the pituitary gland to produce more of its own endogenous FSH. It also temporarily increases the amount of androgen available within the follicular environment, which can potentially increase follicular sensitivity to FSH.

In IVF, letrozole can therefore be used alongside gonadotropin injections in selected stimulation protocols. It is particularly useful when we want to reduce estrogen exposure, such as in patients with estrogen-sensitive conditions, and it may also be incorporated into protocols for selected patients with a previous poor or suboptimal ovarian response.

Letrozole should not be thought of as a medication that universally increases egg numbers or improves egg quality. Its usefulness depends on the individual patient and the objective of the stimulation protocol.

Estrogen Priming

Estrogen priming is performed before ovarian stimulation begins, usually during the latter part of the menstrual cycle preceding IVF. A small amount of estradiol is administered as a gel, transdermal patch or as tablets for several days (usually less than a week) and then discontinued around the time the next treatment cycle begins.

The purpose is somewhat different from giving estrogen during an embryo-transfer cycle. In this setting, estrogen is used primarily to temporarily suppress the natural rise in FSH that occurs toward the end of the preceding cycle. Without priming, some follicles may begin developing earlier than others before IVF medication has even started. When stimulation subsequently begins, this can result in an uneven group of follicles, with one or two follicles growing ahead while others remain considerably smaller. By moderating this early FSH rise, estrogen priming can help synchronize the small antral follicles before stimulation, so that more of them begin responding to gonadotropins at approximately the same stage and we can avoid having an unsynchronized cohort of follicles where some grow earlier than the others and we cannot take advantage of all the follicles available to us.

This strategy can be particularly useful in women with reduced ovarian reserve, a tendency toward early dominant-follicle selection, or previous IVF cycles showing markedly asynchronous follicular growth. The objective is not to increase the ovarian reserve itself, but rather to make better use of the follicles that are available in that particular cycle.

At the same time, estrogen has a suppressive effect on the pituitary-ovarian axis. Excessive or prolonged priming may therefore be counterproductive in a patient with very limited ovarian reserve, particularly if she is sensitive to suppression. For this reason, the dose, duration and suitability of estrogen priming should be individualized rather than routinely included in every IVF protocol.

Growth Hormone

Growth hormone (GH) may occasionally be used as an adjunct to ovarian stimulation, particularly in selected women with diminished ovarian reserve, a previous poor ovarian response, or unexpectedly poor oocyte or embryo development in previous cycles. Growth hormone interacts with the IGF-1 signaling pathway within the ovary and may enhance the responsiveness of granulosa cells and developing follicles to FSH, potentially supporting follicular development and oocyte maturation.

There is considerable variation in how growth hormone is used. Shorter protocols introduce GH at or shortly before the beginning of ovarian stimulation and continue it during the stimulation period. Longer pretreatment protocols may begin several weeks before stimulation, based on the rationale that earlier exposure could influence the follicular environment during the stages of development preceding gonadotropin-dependent growth. However, the optimal dose, timing, and duration have not been established.

Some studies and meta-analyses in women with poor ovarian response have reported increases in the number of retrieved and mature oocytes and, in some analyses, improved pregnancy or live birth rates. However, the quality and consistency of this evidence remain limited, and other randomized trials have failed to demonstrate a clear improvement in live birth. Growth hormone is therefore not routinely required during IVF stimulation but may be considered as an individualized adjunct in carefully selected patients, particularly following a previous suboptimal response.

Androgen priming with transdermal testosterone

Probably the most interesting additional pharmacologic adjunct. Androgens can potentially increase granulosa-cell FSH receptor expression and support early follicular development. It has mainly been studied as pretreatment for poor responders/diminished ovarian reserve, commonly for roughly 2–8 weeks before stimulation. Some meta-analyses have suggested improved ovarian response and pregnancy/live-birth outcomes, but results remain inconsistent across the population, meaning, androgen priming is unlikely to be equally beneficial for every patient. The 2025 ESHRE guideline therefore still does not recommend routine testosterone pretreatment, despite acknowledging some favorable trial data.

Its potential value may partly depend on the patient’s existing androgen environment. Women with relatively low baseline testosterone or DHEA-S levels may theoretically have more to gain from supplementation than women who already have adequate or elevated androgen levels. Baseline androgen levels can therefore be considered alongside ovarian reserve and previous treatment response when deciding whether androgen priming is appropriate. There is no established testosterone or DHEA-S threshold that reliably identifies women who will benefit. Androgen priming should therefore be regarded as a selective, individualized adjunct rather than a routine component of IVF stimulation.

DHEA pretreatment

This is another androgen-based strategy that has been investigated particularly in women with diminished ovarian reserve or a history of poor ovarian response. DHEA is a relatively weak androgen produced primarily by the adrenal glands and serves as a precursor from which the body can produce more potent androgens, including testosterone, as well as estrogens. The proposed rationale in IVF is that improving the intraovarian androgen environment can support early follicular development, increase follicular sensitivity to FSH, and potentially improve the response to ovarian stimulation.

Unlike testosterone priming, which provides testosterone directly, most commonly through a transdermal gel, DHEA relies on the patient’s own steroidogenic pathways to convert DHEA into downstream androgens. This means that the hormonal response to DHEA can vary considerably between individuals. DHEA is also generally used for a longer pretreatment period, commonly several weeks to approximately up to 2-3 months before ovarian stimulation, whereas testosterone priming protocols have often used shorter pretreatment periods.

Before considering treatment, it can be useful to assess the patient’s existing androgen status, including DHEA-s and total testosterone, with SHBG and albumin allowing assessment or calculation of free or bioavailable testosterone when appropriate. This can help identify patients who already have an adequate or elevated androgen environment, in whom additional androgen supplementation may be less biologically compelling. If DHEA is prescribed for an extended period, androgen levels can also be reassessed to ensure that supplementation is not producing excessive androgen exposure.

Some earlier studies and meta-analyses suggested improvements in ovarian response and pregnancy outcomes, particularly among women with poor ovarian response. However, more recent higher-quality evidence has been considerably less convincing. A 2024 Cochrane review concluded that DHEA probably produces little or no improvement in live birth or clinical pregnancy in poor responders, and the updated ESHRE guideline does not recommend its routine use before or during ovarian stimulation. For this reason, DHEA pretreatment is better viewed as a targeted approach to addressing an inadequate androgen environment in selected patients, rather than as a treatment that universally improves IVF outcomes. Its use should ideally be guided by the patient’s baseline androgen profile, ovarian reserve, and previous response to stimulation, rather than being prescribed routinely to all women undergoing IVF.

Mitochondrial Support Protocols

Our Clinical Director, Dr. Ahmet Ozyigit, has developed a comprehensive oocyte mitochondrial support protocol for selected patients, particularly women in more advanced reproductive age groups. The protocol is designed to support cellular energy metabolism, mitochondrial function, antioxidant defense, and other biological pathways involved in maintaining a favorable environment for oocyte development.

The protocol reflects Dr. Ozyigit’s multidisciplinary academic and clinical background. In addition to his medical training, he holds postgraduate qualifications in Clinical Embryology and Endocrinology, is a Fellow in Anti-Aging, Metabolic and Functional Medicine (FAAMM), and is American Board-certified in Anti-Aging and Regenerative Medicine (ABAARM). This combination of clinical embryology, reproductive and endocrine medicine, and longevity medicine has informed an approach that considers oocyte development not only from a reproductive perspective, but also in the context of mitochondrial biology, cellular metabolism, oxidative stress, and the age-related changes that occur within the follicular microenvironment.

It is important to emphasize that mitochondrial support cannot reverse ovarian aging or guarantee an improvement in oocyte quality. Rather, the objective is to optimize potentially modifiable aspects of the metabolic and cellular environment in which oocytes develop, particularly during the months preceding ovarian stimulation.

More information about the rationale and components of this approach can be found on our Oocyte Anti-Aging Protocols page.

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Monitoring Your Response

Ovarian stimulation is not simply a fixed course of medication. The ovaries must be monitored throughout treatment. Transvaginal ultrasound is used to determine the number and size of developing follicles in each ovary and to assess the endometrium. Where required, blood tests for estradiol (E2), LH and progesterone provide additional information. Estradiol helps assess the hormonal activity of the developing follicular cohort. LH monitoring can identify an unexpected LH rise, while progesterone can help detect premature luteinization. Together, these findings allow your physician to decide whether medication doses should be maintained or adjusted and when the follicles are ready for final maturation. Therefore, all of our own-oocyte cycles will include a number of trans-vaginal scans as well as measurements of LH, E2 and progesterone.

The Trigger Injection

When an appropriate number of follicles have reached suitable sizes, a trigger injection is administered to initiate final oocyte maturation. Depending on the protocol and the patient’s individual circumstances, this may involve hCG, a GnRH agonist, or a combination of the two. Timing is extremely important. Egg retrieval is scheduled according to the exact time of the trigger injection, commonly approximately 35-36 hours later, before spontaneous ovulation occurs. For this reason, the trigger injection should be administered at precisely the time instructed by your medical team. You can find more information on our trigger strategies on our “When Is the Right Time to Trigger” blog article.

Egg Retrieval and Fertilization

Egg retrieval is performed under ultrasound guidance, usually with intravenous sedation. A needle is passed through the vaginal wall into each accessible follicle, and the follicular fluid is aspirated. The embryology team then examines the fluid to identify the oocytes. Not every follicle necessarily contains an oocyte, and not every retrieved oocyte will necessarily be mature. Mature oocytes are subsequently fertilized using ICSI where a selected sperm is injected directly into the oocyte. Embryo development is then monitored over the following several days and suitable embryo(s) are transferred either on the same cycle or at a later date for pregnancy. This finalizes the IVF process.

PART 2: Endometrial Preparation for a Fresh or Frozen Embryo Transfer (FET)

An endometrial preparation cycle is different from an ovarian stimulation cycle. In an ovarian stimulation cycle, medications are used to stimulate the ovaries to produce multiple eggs. However, this is not necessary when a patient already has frozen embryos from a previous IVF cycle, or when donor eggs are being used to create the embryos.

In these situations, our focus is not on the ovaries. Instead, the aim is to prepare the lining of the uterus (the endometrium) for embryo transfer. The endometrium needs to develop appropriately and, importantly, its timing needs to be carefully matched with the stage of the embryo being transferred. This helps create the right conditions for the embryo to attach to the uterine lining and establish a pregnancy.

There are several different ways in which we can prepare the endometrium for embryo transfer.

Natural-Cycle Embryo Transfer

For patients who have regular periods and ovulate normally, it may be possible to prepare for embryo transfer without using estrogen medication. Instead, we follow the body’s natural cycle. The growth of the follicle and the timing of ovulation are monitored using ultrasound scans and, when needed, hormone blood tests. Once we know when ovulation will occur, or has occurred, we can carefully time the embryo transfer so that the development of the uterine lining is synchronized with the age of the embryo being transferred.

Sometimes, an hCG trigger injection is given to help control the timing of ovulation more precisely. This is known as a modified natural cycle.

One advantage of this approach is that the uterine lining develops using the patient’s own hormones, without the need for additional estrogen. After ovulation, the follicle naturally forms the corpus luteum, which produces progesterone and helps support the uterine lining during early pregnancy.

However, this approach works best when ovulation is reasonably regular and predictable, and it usually requires closer monitoring. If the body’s own progesterone production is not considered sufficient, additional progesterone supplementation may also be prescribed.

Medicated or Hormone-Replacement Endometrial Preparation

In a medicated endometrial preparation cycle, hormone medications are used to prepare the lining of the uterus and control the timing of embryo transfer. This approach may be used for the transfer of a previously frozen embryo or when embryos are being created using donor eggs.

The aim is the same in either situation: to carefully coordinate the development of the endometrium with the developmental stage of the embryo that will be transferred.

Step 1: Cycle Control or Suppression

In some patients, particularly younger women who continue to have regular menstrual cycles, medication may first be used to temporarily suppress the natural activity of the ovaries. This helps prevent an unexpected follicle from developing or ovulation occurring before we are ready and gives us greater control over the timing of treatment. Not every patient needs this step. Women who no longer have regular menstrual cycles or who have entered menopause will generally not require ovarian suppression and can usually proceed directly to estrogen treatment.

Step 2: Estrogen

Estrogen is then used to help the lining of the uterus grow and develop. Estradiol valerate is commonly used, although other forms of estrogen may also be prescribed. After a period of estrogen treatment, an ultrasound scan is performed to check the thickness and appearance of the endometrium. Before progesterone is started, a well-developed lining often has a characteristic three-line or “trilaminar” appearance on ultrasound. There is no single endometrial thickness that can guarantee implantation. We therefore consider the thickness and appearance of the lining together with the patient’s individual circumstances when deciding whether the endometrium is ready.

Step 3: Progesterone

Once the endometrium is ready, progesterone is started. This is a particularly important and time-sensitive part of the treatment. Progesterone changes the uterine lining from a growing lining into one that is biologically prepared to receive an embryo. The number of days of progesterone must be carefully matched to the developmental stage of the embryo. In simple terms, the embryo and the uterine lining need to be at the right stage at the same time. For this reason, it is very important to start progesterone on the exact day instructed and use it according to your treatment calendar.

Step 4: Embryo Transfer

Once the appropriate duration of progesterone treatment has been completed, the embryo is transferred into the uterus. Depending on the treatment being performed, this may be a previously frozen embryo that has been thawed or an embryo that has been freshly created using donor eggs. Embryo transfer is normally a short procedure that does not require anesthesia. Ultrasound guidance is commonly used to help position the embryo within the uterine cavity. After the transfer, estrogen and progesterone are continued according to the treatment plan to support the uterine lining and the early stages of pregnancy.

In some women, we may often observe a suboptimal response to standard estrogen-progesterone preparations and some women just won’t get the expected trilaminar appearance with an ideal thickness to allow for a successful transfer. We call this the “resistant endometrium” and usually offer some approaches to overcome this problem. More can be found on our blog article titled “The Resistant Endometrium: When Standard Preparations Fail to Build a Sufficient Endometrial Thickness and Appearance”.