Adenomyosis 360

20 Feb 2023

20 Feb 2023

by Dr. Oybek Rustamov in Fertl Edu

This is a comprehensive blog written for women diagnosed with adenomyosis. I cover each and every aspect of the disease. You can safely bookmark this blog as your main resource in dealing with adeno.

In this blog, I will cover the following:

To explain what adenomyosis is, we should first review the anatomy and the function of a normal uterus. Let’s start.

Anatomy of the Uterus

A uterus is a pear-shaped hollow organ measuring approximately 8 cm long, 5 cm wide, and 4 cm deep. It has the following four (4) tissue layers:

The perimetrium is a thin layer covering the uterine wall’s surface facing into the pelvis. Next, the outer myometrium is a muscular uterine wall under the perimetrium which functions in carrying pregnancy and contractions during childbirth. This layer’s muscle fibers are long, strong, and mainly arranged in a longitudinal, or up and down, direction.

Next, the inner myometrium is a muscular wall of the uterus under the outer myometrium. To understand the cause, symptoms, diagnosis, and treatment of adeno, we should have full knowledge on this uterine layer. Bear with me.

We should distinguish the function and anatomy of this layer from the outer myometrium. 

As a main function, this layer assists in transporting the sperm and embryo and in creating an environment for implantation. To fulfill this role, the inner layer has specific cells and muscle fibers that are distinctly different from the outer myometrium.

Muscle cells, or myocells, of the inner myometrium have a large nucleus and are high in water content compared to the outer myometrium. The muscle fibers are shorter and arranged in a transverse, or side-wise, direction. Hence, when the inner myometrium contracts, the inner wall of the uterus moves in the form of a wave. This is essential for transporting the sperm and embryos.

This layer also has two more names: junctional zone and transitional zone. All of these three names mean the same thing – the inner muscle layer adjacent to the endometrium.

Moving on, the endometrium is a glandular and stromal layer that covers the uterus’ inner surface, consisting of two layers.

The basal endometrium is a layer of endometrial cells densely attached to the inner myometrium. This layer consists of stem cells with the property of regeneration. Under the influence of rising estrogen levels every month, the basal endometrium grows a new layer of cells starting from the first day of the menstrual cycle. These cells are called functional endometrium.

The functional endometrium covers the innermost surface of the uterus, or the uterine lining. Normally, the uterine lining grows to approximately 7 to 14 mm until ovulation, then undergoes a change to prepare for implantation. If implantation does not take place, the functional endometrium detaches during the menstrual period and leaves the basal endometrium behind.

Having discussed the structure and anatomy of the uterus, let’s now discuss the normal function of the uterus. This will help us understand how adenomyosis affects both the structures and functions of the uterus.


IMAGE 1. Female Reproductive Structures.

Functions of the Uterus

The main functions of the uterus include providing a passage for sperm to the fallopian tubes, transporting the embryo back to uterus, embryo implantation, placentation, carrying pregnancy, and childbirth.

Let’s explore each function one by one.

Transportation of Sperm and Embryos

This is mainly the function of the inner myometrium, basal endometrium, and functional endometrium layers of the uterus.

In the first half of the menstrual cycle or the first 14 days leading up to ovulation, growing ovarian follicles produce estrogen. With rising estrogen levels, the inner myometrium contracts in a specific manner and creates waves from the cervix to the fallopian tubes at the top of the uterus. This creates negative pressure inside the uterine cavity which sucks in the sperm deposited in the vagina and pumps it into the fallopian tubes.

After ovulation, the ruptured follicle undergoes a transformation called corpus luteum. This cystic structure of the ovary produces the progesterone hormone. With rising progesterone levels, the inner myometrium contracts in the opposite direction. This time the wave-like movement is directed from the top of the uterus to the lower part.

This again, creates negative pressure inside the uterine cavity and pumps the embryo from the fallopian tubes into the uterine cavity. So, one of the main roles of the inner myometrium is making the uterus act as a pump which sucks sperm into the uterus, pushes it towards the fallopian tubes, and sucks fertilized eggs into the uterine cavity.


By the time the embryo reaches the uterine cavity, the surface of the endometrium undergoes certain changes to create an optimal environment for implantation.

The endometrium secretes nutrients for the embryo and creates favorable immune conditions to allow the embryos to attach. The implantation is directly governed by a concert of actions of the pituitary hormones (FSH and LH), ovarian hormones (estrogen and progesterone), the structural changes in the endometrium and inner myometrium, and the embryo.


Given its role, the uterus is rich in blood supply.

Blood vessels of the myometrium branch into small basal arteries at the level of the endometrium. During each menstrual cycle, the basal arteries grow spiral arteries in the functional layer of the endometrium.

During implantation, after attachment to the functional endometrium, the placental cells of the embryo start growing tiny blood vessels to connect to the uterus’ spiral arteries. A rich network of blood vessels on the endometrial bed provides sufficient blood supply and nutrients to the fast-growing embryo.

Carrying Pregnancy and Childbirth

A healthy uterine anatomy provides an optimal environment for carrying a pregnancy to full term and normal uterine contractions during childbirth

Congratulations! Having come this far, you achieved a lot. With the knowledge you gained on the normal uterus, you can easily understand what adeno is and how you can manage it.


IMAGE 2. Implantation of embryo and the endometrial structure.

What is Adenomyosis?

In a normal uterus, each layer should be arranged in its place. But in adenomyosis, some of the endometrial cells end up out of place.

Normally, the endometrial cells do not grow beyond the basal endometrial plate. These cells growing in the normal location of the uterus’ inner surface are called eutopic endometrium. In adeno, the endometrial cells invade the myometrium layers. Now, the endometrial cells growing outside the normal location are called ectopic endometrium.

In adenomyosis, ectopic endometrial tissue grows in the muscle wall of the uterus and causes structural and functional problems.

Depending on the location, the character and growth extent of the ectopic endometrium adeno have the following types.

Adenomyosis is considered as mild if there are only a few small isolated focal ectopic endometrium. We call it moderate when there are several, larger focal adeno. The presence of diffuse ectopic endometrium throughout the inner or outer myometrium and adenomyoma are classified as severe adenomyosis.


IMAGE 3. Quick comparison with adenomyosis & without adenomyosis.

What is the cause of Adenomyosis?

The exact cause of adeno is not known. But, we have several working theories to explain why the endometrium may end up in the wrong parts of the uterus.

01 Embryonic

The uterine structure and layers are formed during the first trimester of the female’s embryonic life.

It is believed that during the embryonic development of women with adenomyosis, some endometrial cells are seeded in the muscle layer of the uterus in error. After puberty, with rising estrogen and progesterone hormones, these endometrial cells gradually activate and cause adeno.

02 Invasion of Normal Endometrium

In a normal uterus, there is a very clear, demarcated border between the basal endometrium and the inner myometrium. Endometrial tissue should not grow beyond this border towards the muscle wall.

For some reason, endometrial cells gradually invade this border by growing towards the muscle wall in women with adenomyosis. It is important to note that adeno cells are entirely benign. However, repeated growth of adenomyosis cells inside the uterine muscle tissue can cause chronic inflammation and erosion of the surrounding endometrial plate.

03 Invasion of Endometriosis

Usually, adeno occurs in women with endometriosis. It is believed that endometriosis and adenomyosis are different forms of the same disease.

It is endometriosis when the ectopic endometrium grows outside the uterus, while adeno is defined as the growth of ectopic endometrium inside the uterine wall. These two conditions often co-exist.

It is estimated that 20 to 80 percent of women with endometriosis have adenomyosis, too. Some believe all adeno starts as endometriosis. Endometrial cells growing in the pelvis and the surface of the uterus gradually grow into the uterine wall and become adenomyosis.

04 Metaplastic Transformation

According to this theory, for some unknown reason, normal cells located in the muscle layer of the uterus undergo transformation into endometrial cells. Once turned into endometrial cells, under the influence of estrogen and progesterone, they multiply every month.

How does Adenomyosis affect the uterine structures?

Normal endometrium of the uterine lining sheds off during periods and excretes as menstrual blood flow outside the body.

However, during the menstrual period, ectopic endometrial tissue detaches and excretes inside the muscle wall of the uterus. Since the muscle layer does not directly communicate with the uterine cavity, excreted ectopic endometrium and menstrual blood accumulate in the middle of the uterine wall.

Since these cells are out of their normal place, the immune system considers them as foreign cells. Immune cells, such as NK cells and macrophages, try to destroy these abnormal cells. By the time the immune cells try to clear the abnormal cells, the next menstrual period occurs and more endometrial tissue gets released. Now, this gradually builds up.

This cycle of endometrial tissue discharges in the uterine wall and the immune cells’ perpetual fight turns the uterine wall into a “battlefield“. This whole process causes chronic inflammation of the muscle cells and the surrounding connective tissue cells. Inflammation of any tissue is characterized by the increased discharge of chemical toxins, swelling of the tissue, and scarring of the surrounding area.

This process gradually erodes the normal structures of the uterus. When you examine women with adeno under a laparoscopy, the uterus typically looks swollen in a round shape called a globular uterus. Also, the uterus looks cherry red and inflamed. Typically, we describe this as an “angry looking uterus” or a uterus with severe adenomyosis.

What are the symptoms?

Adeno causes three main symptoms: pelvic pain, heavy menstrual bleeding, and infertility. However, 30 percent of women with adenomyosis may not have any symptoms, and instead, be detected during an investigation of other pelvic problems

Pelvic Pain

Painful menstrual period in adeno is associated with the inflammation of the uterus. Such inflammation causes increased pressure in the uterine wall. Also, adenomyosis is often associated with endometriosis which can be the source of pain during the menstrual period. 

Women with adeno also report pain during sexual intercourse.

Since adenomyosis and endometriosis are different forms of the same disease, they often co-exist. Pelvic pain during intercourse is often the sign of endometriosis affecting pain nerves in the pelvic floor. In addition, the contraction of the uterus during intercourse can cause increased pressure in the inflamed uterine wall and triggers the pain response.

Heavy Menstrual Bleeding

In adeno, heavy bleeding is caused by the enlargement of the uterus and the impairment of uterine contractions.

The collection of endometrial cells in the uterine wall and the swelling of the uterus increase the overall volume. This increases the surface area of the endometrial lining and results in shedding a larger amount of uterine lining during the menstrual period. This manifests as heavy bleeding.

During menstrual bleeding, the inner myometrial muscle fibers contract and close the basal endometrial arteries like a ligature. Adenomyosis of this junctional zone can impair the muscle fibers’ structure and function and now, cannot stop the bleeding as effectively. These are the main causes of heavy menstrual bleeding in adeno.

Adenomyosis may also cause unscheduled bleeding between periods. This usually happens in women with adenomyoma or cystic diffuse adeno. In these forms of adenomyosis, menstrual fluid gets entrapped inside the caverns of adenomyotic tissue. If these adenomyotic lesions are communicating with the uterine cavity, the fluid discharges during uterine contraction. Typically, adenomyotic discharge is an old chocolate-colored or port-wine coloured fluid.


Infertility is the most common symptom of adeno. Since most women are not aware of the adenomyosis’ existence, they do not know about the disease until it affects their fertility

How common is Adenomyosis in women with infertility?

We don’t know. The more we are learning about adeno, the more common it appears to be. It must have been one of the most common causes of infertility all along, but we didn’t know.


This is because we did not know much about it until recently. The most common way of diagnosing adenomyosis is through a high resolution ultrasound scan and a pelvic MRI. Both of which have become available more recently. 

In the past, we diagnosed adeno in the uterus’ histology in women who had a hysterectomy for painful and heavy periods. With that, we assumed it was a disease of older women with period problems. In fact, we did not know that many women had it and they were not diagnosed unless they had a hysterectomy.

Today, the most common time of diagnosis is during an investigation of infertility. It is estimated that up to 20 percent of women with infertility are diagnosed with adenomyosis. In 20 to 25 percent of women undergoing IVF treatment, a detailed ultrasound and MRI scan find signs of adeno.

In other words, it is very common. Therefore, all women with infertility should have high suspicion of adenomyosis and actively look for signs. 

Method of Diagnosis


Adenomyosis can be such an elusive disease, you do not see it unless you look for it.

The most important factor in diagnosis is having a high level of suspicion for women in high-risk groups. Doctors should investigate if you have any of these adeno symptoms: history of endometriosis, heavy menstrual bleeding, painful periods, and infertility.

Detailed and directed history-taking can reveal other symptoms of endometriosis which often affects women with adenomyosis. The Endopain-4D questionnaire is an excellent tool for diagnosing endometriosis and adeno.

Pelvic Exam

A uterus with severe adenomyosis has specific features that can be detected during a pelvic exam.

An enlarged, globular, and soft uterus accompanied by pain during the examination are the signs of diffuse adeno. The mild to moderate focal adenomyosis cannot be detected during a pelvic exam. A more reliable investigation, ultrasound imaging, is recommended for all women with symptoms.

Ultrasound Scan

A pelvic ultrasound for adeno uses a vaginal ultrasound probe for a close examination of the uterine structures.

Although a vaginal scan provides high resolution imaging, small focal adenomyosis may not be seen. However, signs of diffuse and severe adeno can be seen clearly. An adenomyotic uterus has a heterogeneous appearance on the scan. Cystic adenomyosis is seen as fluid-filled areas in the myometrium.

An adenomyoma can also be clearly visualised as a round-shaped cyst in the uterine wall surrounded with a capsule. This type may look like a fibroid. In addition, adeno and uterine fibroids often co-exist. Hence, it may not always be possible to tell if the abnormal structure is an adenomyoma or uterine fibroids.

One of the common types of the disease is diffuse adenomyosis of the junctional zone. An ultrasound is not the best type of imaging to detect this as it is difficult to distinguish the abnormal inner myometrium. However, an MRI of the uterus can detect all forms of adeno. While the diagnostic accuracy of ultrasounds is around 80 percent, an MRI is at 90 percent accuracy in diagnosing adenomyosis.

Most importantly, if you have adeno symptoms, you should tell the sonographer. This allows them to actively look for signs of the adenomyosis and improves the diagnostic accuracy of the ultrasound imaging.

MRI of the Pelvis

Magnetic Resonance Imaging (MRI) is the best method of investigation for adeno. An MRI can see through the soft tissues and can detect even the smallest adenomyotic lesions. 

With that, an MRI is considered as a Gold Standard Test for adenomyosis. However, again, the radiologist should be informed that the MRI is being done to investigate adeno. This allows the radiologist to use a special form of MRI to visualize adenomyosis lesions.

The most common and elusive form of the disease is adeno of the junctional zone. In this type of adenomyosis, the ectopic endometrium has grown through the endometrial plate and towards inner myometrium. On an MRI, this form is seen as the haziness of the border between the endometrium and myometrium.

Normally, the junctional zone should be thinner than 12 mm and should be fairly uniform in thickness in all parts of the inner uterine surface. The difference between the thinnest and thickest part of the junctional zone should not exceed more than 5 cm. Radiologists diagnose adeno if the junctional zone is larger than 12 mm in any part or if the maximum difference between the parts of the junctional zone exceeds 5 mm.

Adenomyosis of the outer myometrium is seen as a heterogeneous change in the muscle wall. Diffuse cystic adeno and adenomyoma can be easily detected on an MRI.

Laparoscopy and Hysteroscopy

Laparoscopy and hysteroscopy can reveal some signs of adenomyosis. However, it is not recommended for the diagnosis of adeno.

Since adenomyosis is the disease of the uterine wall, the lesions cannot be directly visualised by looking at the surface of the uterus (laparoscopy) or inside the uterus (hysteroscopy). However, in women undergoing laparoscopy or hysteroscopy for other reasons, signs of adeno can be seen.

In the presence of severe adenomyosis, the uterus is enlarged, globular in shape, inflamed, and red. These types of changes in the uterus only happen if you have severe adeno. Mild to moderate adenomyosis may not have any external signs and may not be detected on a laparoscopy at all.

In women with severe adeno, especially with a large adenomyoma, some signs of the disease can be seen on a hysteroscopy. For severe adenomyosis, a hysteroscopy can show an enlarged uterus. Occasionally, in women with cystic adeno or adenomyoma, you can see chocolate-colored fluid weeping from the uterine wall into the uterus during a hysteroscopy. But, this is rare.


IMAGE 4. Diffuse adenomyosis on an MRI.


In women who underwent a hysterectomy, the examination of the uterus under a microscope can show adenomyotic lesions. Histology can definitively diagnose adenomyosis. Since hysterectomy involves the removal of the uterus, women desiring to have children in the future cannot have this treatment.

Treatment of Adenomyosis

Adeno mainly causes three different types of problems: pelvic pain, heavy menstrual bleeding, and infertility. As treating these symptoms need different approaches, I suggest we first discuss pelvic pain and heavy periods, then explore the treatment of infertility.

Pelvic Pain and Heavy Periods

Treating pelvic pain and heavy periods in women with adenomyosis depends on whether they are actively trying to conceive (TTC) or if they are planning to have any children in the future. Therefore, I have divided women with adeno into three groups with different types of recommended treatments.

Women actively trying to conceive (Group 1) can only have painkillers and tablets to reduce the bleeding. If they need a more effective treatment, hormonal medications in the form of combined estrogen and progestin preparations are the next line of treatment.

Progesterone-containing intrauterine system, Mirena IUS, is effective in treating both painful periods and heavy menstrual bleeding. If the pain and bleeding symptoms are not relieved with the above treatment, GnRH agonist injections are indicated. This treatment is very effective as it shuts down the ovaries, blocks the cyclic production of estrogen, stops menstrual periods, and hence, prevents the growth of adenomyosis.

However, hormonal treatments and GnRH agonist injections can affect fertility. With that, they are not recommended for women actively trying to conceive. If you would like to get a break from pain or bleeding symptoms, you can use these treatments. After the completion of hormonal treatment and GnRH agonist, fertility restores and you can continue trying to conceive.

If you are not actively trying to conceive, but wish to have children in the future (Group 2), you can use painkillers, medications for reducing the bleeding, hormonal preparations, and the GnRH agonist treatment. You should certainly avoid irreversible treatments such as endometrial ablation and hysterectomy.

Women who have completed their family (Group 3) can consider all types of treatment. Women with heavy periods not relieved with hormonal treatment can have endometrial ablation. Since an endometrial ablation irreversibly affects fertility, this treatment is only recommended to those 100 percent sure that they do not want to have any more children in the future. 

Uterine surgery for removing adeno can be considered by women with isolated adenomyoma. However, any uterine surgery for adenomyosis can cause severe scarring of the uterus, including adhesions to the uterine cavity. This is known as the Asherman syndrome. Therefore, surgical treatment of adeno is strongly contraindicated in women planning to have children in the future.

The last resort treatment is total hysterectomy. Since hysterectomy is the complete removal of the uterus, it treats pain and all bleeding symptoms. However, the decision of a hysterectomy is a serious and irreversible step. Women planning to have any children in the future should not consider this treatment. 

Treatment of Adenomyosis

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Pelvic Pain and Heavy Periods

How does adeno affect fertility?

Adenomyosis affects fertility in 7 levels.

Abnormalities can lead to infertility due to the impaired transportation of sperm and embryo, failed implantation of the embryo, and failed placentation. Let’s review how adeno can cause these problems. 

Impaired Transportation of Sperm and Embryo

Because of inflammation and scarring of the inner myometrium, the muscle fibers become damaged and cannot contract normally. Consequently, the uterus’ “pump system” does not function properly which affects the transportation of the sperm and embryo. The impairment of sperm transportation can cause infertility. Abnormal transportation of the embryo can result in an ectopic pregnancy.

Failed Implantation

Adenomyosis can cause physical, biochemical, and immunological obstacles for the implantation of the embryo.

The growth of ectopic endometrium and chronic inflammation can cause structural erosion of the endometrial bed. This can create physical barriers for implantation. Additionally, various inflammatory chemicals are released into the endometrium during inflammation. This can impair the embryo’s survival during the initial critical stages of its development.

The maternal immune cells’ recognition of the embryo and allowing it to implant involves a complex interaction called the cross-talk between embryo and endometrial cells.

Numerous types of immune cells, like NK Cells and macrophages, are involved in the process of implantation. Due to chronic inflammation in the surrounding tissues, adeno causes an impairment of the immune response towards implanting the embryo. It is believed that in some women, immune causes of repeated implantation failure is associated with adenomyosis.

Failed Placentation

Normal growth of the embryo’s placenta involves the attachment and growth of placental cells in the endometrial plate. In adeno, the process of placentation may be affected due to structural changes and the inflammation of the endometrial bed. Hence, women with adenomyosis are at an increased risk of losing pregnancy at early stages. This is diagnosed as biochemical pregnancy or miscarriages.

Treatment of Infertility

Some women can conceive naturally despite having adeno.

Women with adenomyosis and infertility can try to conceive naturally, provided they do not have any other causes of infertility. However, given the negative impact of adeno, the couples should have a low threshold for seeking fertility help.

If a successful pregnancy is not achieved after trying for 3 to 6 months, they should consider fertility investigation and treatment. If adenomyosis is the main cause of infertility, the most effective treatment is IVF.

IVF & Adenomyosis

Let’s explore the association between repeated implantation failure and adeno in more detail.

In IVF cycles, the success of implantation is mainly determined by the quality of embryos. You can expect approximately a 1 in 3 chance of a successful pregnancy with a high-grade embryo transfer. If embryos do not implant after repeated transfers, then you should suspect that there are additional causes for failed implantation. 

If implantation does not occur after the transfer of more than two high-grade blastocyst embryos, women are diagnosed with repeated implantation failure. This diagnosis starts investigations to find possible causes of failed implantation. After the investigation, most women with repeated implantation failure are found to have adenomyosis or severe endometriosis.

Given it is common pathology, affecting 25 percent of women undergoing IVF treatment and its detrimental effect to the uterus, adeno is the most common cause of repeated implantation failure. Women with adenomyosis have on average a 50 percent lower chance of implantation of embryos.

For instance, after the transfer of a high grade-embryo, women at the age of 35 have approximately a 30 percent chance of successful pregnancy. In women of the same age with adeno, the odds of success is reduced by 50 percent, meaning they have a 15 percent chance of a successful pregnancy – on average. 

Depending on the severity and the location of the adenomyosis, this can range from a very minimal chance of implantation to close to normal odds.

Overall, this suggests that women with adeno may need to have more embryo transfers to achieve a healthy baby compared to other women. To improve the odds of success per embryo, women should consider having full treatment of adenomyosis before transferring the embryos.

Generally, there are two approaches in IVF treatment for women with adeno: Routine IVF Treatment & Three Stage IVF + Adenomyosis Treatment.

The decision on the approach depends on factors that determine the odds of obtaining high-grade embryos and the chances of implantation. Careful consideration of factors listed in the following image is crucial in making the most optimal decision for each couple. 


Routine IVF Treatment

Routine IVF Treatment involves embryo transfer without pre-treatment of adeno.

This can be the right treatment option in women with mild adenomyosis and without a history of repeated implantation failure. Women with a high ovarian reserve who can produce high-grade embryos without difficulty can try embryo transfer without treating adeno first. If they are not successful, then they can consider the three-stage protocol. 

Three Stage IVF & Adenomyosis Treatment

Each embryo is a potential baby and we should create the best possible environment for their implantation.

Since adeno can wreak havoc in the uterus and the implantation bed, best we treat adenomyosis first before embryo transfer. This is especially true for moderate to severe adeno, co-existing severe endometriosis, and previous history of repeated implantation failure.

Women with a low egg reserve or more advanced reproductive age may not be able to produce high-grade embryos easily. With that, these factors indicate that we should take extra care in ensuring the implantation bed is in its most optimal state possible. 

Yes, adenomyosis may have a devastating impact on implantation. Equally, there is an effective treatment available. Shutting down the reproductive hormones for a while appears to cure adeno. Although the effect does not last long, it gives us a sufficient window to achieve successful implantation and pregnancy.

This treatment is achieved using monthly injections of GnRH Agonist Drugs (Zoladex, Prostap, Lupron). GnRH agonist drugs completely block the production of pituitary hormones, FSH and LH. Without FSH and LH, ovaries cannot grow follicles and cannot produce estrogen and progesterone. Since adenomyosis can only grow with estrogen and progesterone, this stops the growth of adeno.

Once adenomyosis stops multiplying, the immune system clears all the damaged cells and heals the inflammation. In the level of genes, reproductive cells are reprogrammed to their original state. When rebooted, instead of causing problems with implantation, they start doing their designated job, helping the implantation of an embryo. Once the inflammation is healed, the immune system also goes back to its normal state. After the full treatment of adeno, the immune cells start assisting implantation instead of impairing it.

To achieve the full treatment effect, we should give GnRH (Zoladex) long enough. The minimum duration is four (4) months. With shutting down the reproductive hormones, the healing of inflammation and the reprogramming of the cells are slow processes; shorter treatment courses are not as effective. GnRH agonist treatments can be given up to six (6) months. 

Since GnRH agonist (Zoladex) switches off estrogen production, women may have side effects during the treatment. These are linked to the lack of estrogen in your body, hence, very similar to menopausal symptoms. GnRH agonists may cause hot flashes, sweating, dryness of skin, reduced libido, vaginal dryness, and irritability. If these symptoms are severe, then the duration of GnRH treatment can be shortened.

You may worry about shutting down your ovaries and think, what if you can’t restart. GnRH (Zoladex) only stops the production of pituitary hormones (FSH & LH) that stimulate your ovaries. It does not affect your ovaries or egg reserve directly. Once the last dose of Zoladex wears off, your menstrual cycle returns.

GnRH agonist have been in use for more than 40 years for treating endometriosis and fibroids. Every year, millions of women use Zoladex. We know for sure that it does not impact your egg reserve or long-term ovarian function.

Let’s discuss the three stage treatment and why it is the optimal strategy for women with moderate to severe adenomyosis. 

In women with severe adeno, the main challenge is achieving implantation. Given this, we should treat adenomyosis before transferring any embryos. The effect of treatment lasts approximately 4 to 6 months after the completion of GnRH (Zoladex) treatment. So, we have 4 to 6 months to achieve a successful pregnancy.

Ideally, we should avoid repeated ovarian stimulation for IVF after GnRH (Zoladex) treatment, as each cycle may speed up the recurrence of adeno. With that, we should have a sufficient number of frozen embryos that we can utilize after the GnRH (Zoladex). Therefore, we should have sufficient amounts of high-grade blastocyst embryos frozen prior to GnRH (Zoladex) treatment. 

I recommend, first, IVF cycles and freezing all of the embryos to try and achieve banking 3 to 4 high grade embryos. This is followed by 4 to 6 months of GnRH (Zoladex) treatment and finally, Frozen Embryo Transfer (FET) cycles to achieve successful implantation and pregnancy.

Generally, in my experience, three stage IVF Treatment gives an excellent chance of pregnancy in women with adenomyosis. This treatment method is very effective, even in women with a long standing history of repeated implantation failure. 


Adeno is a common, yet elusive, reproductive disease which causes pelvic pain, heavy menstrual bleeding, and infertility. It can cause significant damage to the structure and function of the uterus.

Adenomyosis can be diagnosed with an ultrasound, however, an MRI is the most reliable imaging method. Treating adeno depends on the symptoms and the desire to have children in the future.

Adeno is one of the main causes of infertility – treating women with adenomyosis and repeated implantation failure can be challenging. However, using effective IVF and GnRH agonist treatments, a successful pregnancy can be achieved, even in women with severe adeno.



Junyu Zhai et al. Adenomyosis: Mechanisms and Pathogenesis. Semin Reprod Med. 2020 May ; 38(2-03): 129–143. doi:10.1055/s-0040-1716687.


Malcolm G Munro. Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity. Fertility and Sterility® Vol. 111, No. 4, April 2019.


Silvia Vannuccini, Felice Petraglia. Recent advances in understanding and managing adenomyosis. F1000Research 2019, 8(F1000 Faculty Rev):283 Last updated: 14 MAR 2019.

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