Uterine factors and IVF options. Diagnostics and treatment options

Alejandra Aguilar Crespo, MD
Gynecologist at Equipo Juana Crespo , Equipo Juana Crespo

From this video you will find out:

Should the septate uterus always be removed?
Should intramural fibroids be operated on?
Can painful periods (dysmenorrhea) affect the uterine function?
Is curettage better for a miscarriage than medical treatment?
What is the optimal endometrial thickness for an embryo transfer?

Uterine factors and IVF options. Diagnostics and treatment options

What if my uterus is a factor in failed IVF cycles?

In this online patient meeting, Dr Alejandra Aguilar Crespo, a Gynaecologist & Consultant Specialist at Equipo Juana Crespo, Valencia, Spain has been talking about uterine factors and their impact on IVF treatment. She has explained how to diagnose and treat them in order to have a successful IVF outcome.

A number of factors can affect the shape and functioning of the uterus, which can lead to infertility. Uterine factor infertility occurs in less than 5% of women. In general, uterine factor infertility can be divided into anatomic causes (fibroids, myomas, adenomyosis and polyps) and functional causes (chronic endometritis). At times, women are born with a bicornuate or unicornuate uterus, those can be surgically corrected. It’s important to remember that fibroid or polyps can interfere with fetal growth and depending on the size and location should be removed.

Diagnosing the cause of uterine factor infertility requires various tests including ultrasonography to evaluate the uterus for fibroid tumours, cysts and other abnormalities. Hysterosalpingogram(HSG), Magnetic resonance imaging (MRI), Sonohysterography, Hysteroscopy or Laparoscopy. Each patient needs to be evaluated individually as not all uterine malformations require to be removed, polyps or fibroids that do not interfere with fertility usually don’t require removal as well.

- Questions and Answers

Should the septate uterus always be removed?

This is the most frequent uterine abnormality. Whether it should be removed depends on the degree of the septum. If it’s a complete septum, removing it will improve the results. So, yes, it should be removed, only if there is a context of infertility or recurrent miscarriage or complication in a previous pregnancy. Sometimes, when we are performing a cesarean section, we can see that this woman has a septum, and we have not seen it, so it doesn’t mean that having a septum can be correlated with infertility. More or less, 25% of women who have a septum can be infertile. It depends on the cause, the history of the patient. Here in our clinic, if we are facing a couple with a history of infertility and we diagnose a septum, it has to be removed.

Should intramural fibroids be operated on?

Again, it depends on the location and the size of the fibroids. If the fibroid doesn’t reach the endometrial cavity, and it’s not very big, it’s less than 3 centimeters, we don’t have to remove it. With the uterine fibroids, you can alter the structure, and you can also alter the uterine architecture depending on the location. Sometimes it’s worth removing it. We also have to take into account the previous history of the patient. If this patient has a previous cycle and failed transfers, we can remove the fibroid. If there is an intramural fibroid that reaches the endometrial cavity, we have to remove it. It can decrease the implantation rate. Even if a fibroid is very, very big, but it doesn’t reach the endometrial cavity, the uterine architecture can be damaged, and the implantation can be affected. In such a case, we have to remove it. We have patients who have only 1 fibroid, and after removing it, she gets pregnant, so sometimes it is worth it, but it depends on the size, location, and previous history of the patient.

Can painful periods (dysmenorrhea) affect the uterine function?

Yes, definitely. Having a painful period means there is a strong uterine contraction. This uterine contraction can sometimes affect uterine function. A very strong uterine contraction can alter uterine architecture. It can provoke adenomyosis and, therefore, can cause fibrosis. If there is adenomyosis or if there’s uterine fibrosis, this can end in implantation failure and miscarriage. If there are several painful periods, a chronic painful period can provoke a dysfunction of the uterus.

Is curettage better for a miscarriage than medical treatment?

We have to take into account that the medical treatment of miscarriage sometimes can provoke strong uterine contractions. These contractions can cause uterine bleeding, and this can damage the uterus. Sometimes, when medical treatment is not enough, curettage, D&C is required. If there is a strong uterine contraction, our advice is to perform a curettage, but you need to keep in mind that it can also damage the uterus. We’ve seen that after medical treatment of the uterus, it can be very damaged, and after that, it can be hard to perform an embryo transfer in that uterus. It depends on each case.

What is the optimal endometrial thickness for an embryo transfer?

There is no real consensus on the endometrial thickness. In normal conditions, we prefer an endometrial thickness from 7 to 14 millimeters. In our clinic, we prefer to have an endometrial thickness from 7 to 10 millimeters. More important is the endometrial appearance than the thickness. The endometrium should be of a triple-layer, it should be trilaminar, and we shouldn’t have any polyps, fibroids. There shouldn’t be any mucus inside the endometrium. If the patient has a very thick endometrium and we cannot make it thin, we can go ahead, it depends.

How likely is it for polyps to come back after a couple of months?

The problem with the polyps is their recurrency. Yes, it can grow back after a couple of months after you remove it. Ideally, in the first two months, if we remove a polyp, they won’t appear. After six months, they can grow back. Some patients have an endometrium with a lot of polyps because the structure of the endometrium is very glandular. It has a lot of estrogens, which can provoke polyps. We have to check very deeply to see if the patient has polyps after a couple of months.

What does constitute abnormal bleeding after a period? Is pink bleeding on day 5/6 normal?

It depends on your periods. Abnormal bleeding in a menstrual cycle is completely normal. Sometimes a patient can have an abnormal cycle, and she can bleed in mid-cycle, or have pink bleeding on days 5-6 six. From my point of view, it’s completely normal. If every cycle is like that, you should see a consultant, and we can perform an ultrasound scan to check that everything is okay. The abnormal bleeding is caused by uterine fibroids, adenomyosis, or polyps. If it’s your first abnormal bleeding probably, it doesn’t mean anything, and if the next period is abnormal, you have to consult a certain specialist.

How could it be prevented during a multiple fibroids surgery that scars that are built can lead to infertility?

It depends if the surgery is done by laparoscopy or hysteroscopy. If we perform a myomectomy during hysteroscopy to prevent the scar tissue. This is very common, we always have to give a contraceptive pill to avoid the uterine adhesions. When we perform surgery, this tissue is very, very sensitive, and it can be very sticky, so we have to give estrogens or a contraceptive pill at least for a month. In our clinic, we also use hyaluronic acid to avoid uterine adhesions or synechia, we can also introduce a balloon, which is a balloon inside the uterus to avoid the synechia. It depends on the degree of surgery, the fibroid. In laparoscopy, we don’t touch the endometrial cavity, we give the contraceptive pill to avoid the uterine bleeding, and that’s all.

Is it possible that polyps recurrency can cause Asherman’s syndrome?

If we remove the polyps, if we perform several hysteroscopies, we can cause Asherman’s syndrome. Asherman’s syndrome is caused by 90% by surgeries, miscarriages. To prevent it, it’s important not to damage the endometrial cavity when we do a hysteroscopy. We can damage the endometrial cavity if we use energy. In our clinic, we never use bipolar scissors, we only use scissors without power because it can burn the tissue, and if we burn the tissue, this could cause scar tissue or an infection. It is better only to use what we call cold scissors to avoid Asherman’s syndrome. Multiple surgeries, hysteroscopies can provoke this syndrome. It always should be performed by a reproductive surgeon.

Could scars that are outside the uterus be a problem during the pregnancy?

You probably mean scars that are outside the endometrial cavity and are in the myometrium. Normally, not. If you have removed a uterine fibroid, possibly not as it cannot affect the pregnancy. After surgery for fibroids removal, it’s crucial to let the uterus heal, we need at least 4 months. It means that after a laparoscopy, after the surgery of the uterus, it’s necessary to wait for at least 4months, in case we are removing fibroids, which are not inside the endometrial cavity. If it’s inside the endometria cavity, we can only wait for 1-2 months. This is to avoid uterine rupture during the pregnancy because when there is a pregnancy, the uterus grows, the uterus is a muscle, so it has to grow, so if there is a scar, it can break, and then there is a big problem, so it’s crucial to wait those 4 months.

Could polyp scars cause a problem with the uterine lining?

Yes, but not only polyp scars. It can also happen with scars after fibroids, scars from the uterine septum, it can provoke adhesions and synechia. It can also cause that the endometrium will not grow because sometimes we damage the zone where the endometrium needs to grow. The endometrium needs to grow, and it happens thanks to the stem cells that are behind the endometrial lining. If we damage these cells, the so-called junction zone, we can damage the uterine lining. That’s why it’s very important to understand what we are looking for when we are performing hysteroscopy. It’s also very important for the hysteroscopy, and surgery to be done by a reproductive surgeon.

I have a 5 cm subserosal fibroid in the isthmic area of the uterus. I had uterine artery embolization is done, which caused me premature menopause. UAE (uterine artery embolization) did nothing to the fibroid. What factors should I consider or has to be examined on the uterus before trying pregnancy with donor eggs?

The problem with uterine artery embolization is that sometimes it doesn’t affect the fibroid, and sometimes it can affect the ovaries, and it can provoke premature menopause because it can kill the oocytes, it’s gonadotoxic. I would need more details as it also depends on your age. If we see that you have follicles, we can try without donor eggs, but if you have menopause, we have to go ahead with donor eggs. Regarding the fibroid, it depends if it’s in the isthmic area, and it’s not reaching the endometrial cavity, we can try as we are going ahead with the donor eggs, so probably your embryos will be of very good quality, so we can try to put the embryo back, also depending on the location of the fibroid. If you don’t get pregnant, my advice will be to remove the fibroid because there is something there that is decreasing the implantation rate. In your case, I would probably ask for an MRI to check that everything is fine before putting embryos back.

Are there treatment options to diffuse adenomyosis with a thick junctional zone (over 30mm) with the chance of maintaining fertility potential?

There are 2 options to treat adenomyosis. There is a medical treatment and surgical treatment, or both. If we try to decrease the estrogens, the adenomyosis will be controlled. The medical treatment would be the GnRH analogs, which is Decapeptyl or Gonapeptyl, it depends on your uterus because, in diffuse adenomyosis, it is better to use medical treatment. In focal adenomyosis, sometimes it’s better to use the surgery to remove it, which is the adenomectomy. The problem with surgical treatment is that the adenomyosis is not like a fibroid. Focal adenomyosis is very vascularized, so the surgery is very difficult. It’s not like surgery to remove the fibroids, which is very easy. It’s like a ball is introduced inside the endometrium with adenomyosis, it’s very difficult, and sometimes we have to remove a complete block of the uterus to remove all the adenomyosis. Therefore, it’s better to do medical treatment for adenomyosis. Sometimes to reduce its size, and then if adenomyosis is still there to perform the surgery. At times, when adenomyomas are located very close to the endometrial lining, we can remove them by hysteroscopy.

Should we carry on with transfer if there’s a small polyp (<1cm)? Is it more likely to fail?

If we are doing a uterine preparation for an embryo transfer and then I see that a polyp is there, I would cancel it, but it depends on your case. It has not been demonstrated that if there is a polyp, the result would be zero, we don’t know. It has been demonstrated that the polyp can and might decrease the implantation rate, so if we have a lot of embryos, we can try. If a patient has a very low ovarian reserve, then every single embryo is very important, so I would cancel it. It doesn’t mean that if there is a polyp, your result will be negative. If there is a negative test, we need to know if it was because of the uterine polyp, embryo, uterus, we don’t know. If there is a potential cause that can decrease the implantation, I will do a hysteroscopy to remove this small polyp.

How long after a fibroid surgery should I wait before starting stimulation for egg banking?

If there is no transfer, you can go ahead, and in the next period, there won’t be a problem with that. As we are not transferring, the uterus won’t grow, so we can go ahead in the next period or next month or even two months.

Would you recommend that a 14cm x 12cm subserosal fibroid to be removed before starting my cycle with donor eggs?

If it’s a complete subserosal, it means that there is no intramuscular component, so we can go ahead. It’s very big, and probably during the pregnancy, it will hurt because of the fibroid compression because it’s very big, and during pregnancy, the fibroid can sometimes grow. If your womb will become very big and then there will be a big fibroid, you will feel bad. This fibroid can provoke nutrient contr action. If it is a complete subserosal fibroid, it depends on the scan, and also, it depends on how many embryos do we have. If you are an egg donor recipient, you will probably have very good quality embryos, so we could try. The surgery of subserosal fibroid is very easy, there are no complications because it’s very easy to remove it. I would probably go ahead with the removal.

Is endometrial hyperplasia a big issue for embryo implantation? How does this condition affect pregnancy? What treatment do you recommend to cure endometrial hyperplasia?

If you have endometrial hyperplasia, my recommendation would be not to go ahead with the embryo transfer. If we don’t treat it after some time, it can even become endometrial cancer. Hyperplasia means that there is a lot of estrogens in your endometrium. The treatment is to give you progesterone, but of course, we need to check that everything is fine, so probably we would do a biopsy of the endometrium. In your case, we should probably prepare your uterus with low doses.

How fast do fibroids grow back after fibroids surgery? What can be done to prevent it from growing back?

It depends on each patient. Sometimes, when we remove this fibroid, you will never have another one, and sometimes after a year, you can have another one. The recurrence does not happen as often as with the polyps, but it can happen. When a person has periods, and she’s 40, the fibroids can come back, they are also estrogen-dependent. That’s why it’s better to give such patients the contraceptive pill to make it stable.

How common is silent endometriosis? If there are no other factors than advanced age (39-42). Would you suggest laparoscopy to explore if it’s endometriosis?

If there is no pain, there is no indication for the laparoscopy, so I wouldn’t suggest it. If there are no endometriomas, big endometrium, no pain when you are in the toilet, or you’re having sex, I wouldn’t suggest that. Laparoscopy is a surgery, it has its complications, we have several tools to diagnose endometriosis like MRI to explore if there is an indication for surgery.

What is the connection between the endometrium lining and periods? I had a normal thickness of endometrium lining but very light periods lasting only 2 days, which seems too short and possibly a problem?

It’s not a problem, your uterus is probably small. Normally, if the endometrial lining is very big, it’s very thick, and sometimes the periods are strong and are heavy, but it’s not always like that. It’s not only about the endometrial lining, but it’s also about the volume of the endometrial cavity. The smaller the uterine cavity is, the shorter periods, so it’s not the uterine lining because, for example, when you are taking the contraceptive pill, your uterine lining is very thin, and you still have periods when you stop the contraceptive pill, so it’s not just because of that. It also depends on your hormonal levels and also of uterine contractility. If your uterine cavity has the correct volume, it should not be a problem.

Is a 4-month wait required for diagnostic laparoscopy or only for treatment? What is the risk of diagnostic laparoscopy in causing damage or scar tissue?

If it’s a diagnosis laparoscopy, it’s safe, it’s only for diagnosis, it is not a surgery. If it is only just to open and see, there is no risk of scar tissue. When we introduce when the object to perform the laparoscopy, the tissue reacts and can cause scars and these scars if they are very big, also because the patient has this type of skin, the tissues can provoke scars, and it can also affect the fallopian tubes, the pelvic and pain. Normally, with only a diagnosed laparoscopy, there is no problem.

How does a history of bacterial vaginosis affect fertility? I have had antibiotics after a microbiota test. Is my next round of IVF likely to be more successful?

It has been demonstrated that vaginosis, which is a disbalance of the endometrial microbiome. We have to take into account that the vagina has its own microbiome as well as the endometrium. Contrary to that, we thought the endometrium has its own microbiome, so it has been demonstrated that after controlled ovarian stimulation, the good bacteria that protect our vagina can be altered and can provoke a disbalance of the endometrial floor throughout the endometrial microbiome and can lead to the bad pathogens to colonize the vagina. This bad pathogen can cause an implantation failure. If you have bacterial vaginosis, it can affect fertility, implantation, it can also provoke miscarriage, so this should be treated. That’s why you were given the antibiotics, and it’s very important to take probiotics in that case, before the stimulation and then before the embryo transfer, make sure that your microbiome is completely fine.

Are polyps, fibroids, and adhesions within the uterus always visible on scans?

It depends on the patient cycle, the moment we are performing the scan. If the scan is performed during the period or the follicular phase, it’s very unlikely. The thicker endometrium is, the easier it is to check these fibroids and the polyps. If the fibroid is big we will always see it. This can be checked by a gynecologist. If there is a very big polyp, we can see them, but if they are less than 1 centimeter, it’s difficult sometimes, and we need a thick endometer to check it. We also have some tools that we can use during the ultrasound scan. Sometimes, some polyps have a vessel, which is called a feeding vessel, it’s feeding the polyp. When we see an image of a vessel and it is in the center of the polyp, it can help to diagnose it. If we are not sure, the best method to diagnose the polyps and fibroids is to perform a diagnosis hysteroscopy, which is only to introduce it and then to see if there is something inside in the endometrial cavity.

I have 2 small fibroids (1.5 and 2 cm, intramural), and usually, my endometrium gets to 7/8 mm after ovulation naturally. To avoid overexposure to estrogens, do you suggest a natural cycle without medications to thicken the lining? I will have a polyp removed in a few days, and I will be close to my period (maybe 3 / 4 days before it). Is that an issue? I don’t want to postpone it due to COVID-19. I want to do a transfer in January (donor eggs). Can the polyp grow back in the meantime? Do you suggest to remove the fibroids? All the doctors said no for now, but I’m unsure.

The fibroids, it’s true, are small, but it depends on the location. If they reach the endometrial cavity, of course, they will have to remove them even if they’re small. I cannot tell you if you have to remove that, it depends on the location and relation to the endometrial cavity. Your endometrium looks well at 7/8 mm after the ovulation, but it is better to check it before the ovulation. Whether, to do a natural cycle, yes, why not. In our clinic, we perform many natural cycles. If we can see that the uterine lining has the correct shape and the right thickness, why not try it. Ideally, the polyps are removed after either in the first part of the cycle, in the follicular phase because the endometrium will be thin, and it will be easy for the surgeon. If they remove it before the period, sometimes the endometrium is very big, and it will be difficult for the surgeon to catch the problem. It’s better if you’re taking the contraceptive pill or if you are after the period between day 7 and day 8 of the period. I don’t think that in 2 months you will have another polyp, it is possible though. That’s why you probably have to check it, but I don’t think that you will have a big polyp in two months.

How long does a high estrogen level stay in the body after egg retrieval? Does it drop right away?

It doesn’t drop right away, that depends on the trigger. If you have been triggered with Ovitrelle, it drops s slowly until the period comes. After Decapeptyl trigger, it drops after five days, we also have some tools to make it to drop faster because, for example, when we are stimulating a patient that has cancer, that has breast cancer, and with the breast cancer, the estrogen doesn’t have to be very very high because we can do some damage to the patient. After the egg retrieval, the patient takes a pill that can drop this estrogen level. If the patient doesn’t have any medical background, higher estrogen levels don’t damage the body, so you don’t have to worry about that. After 5 to 15 days, the period will come, and then the estrogen will be completely fine. Normally, after Decapeptyl injection, it’s 5 days, and with the Ovitrelle injection between 10 to 14 days.

My endometrium lining on day 9 of treatment was 10.76, it was growing roughly 2 per day between days 3 and 9. For the 7 days between then and transfer. Do you think this would likely grow at the same rate?

It depends if your endometrium is thick at the beginning. After the introduction of the progesterone, the endometrium compacts, which is the functionality of the progesterone. Sometimes this endometrium can grow a lot because it has a lot of estrogens. This is not good for an embryo transfer. That’s why if we were facing a thick endometrium, we prefer to see the patient the day before or on the day of the transfer, just to confirm that the endometrium is okay, and then we perform the transfer. It can grow fast, but normally, it doesn’t happen. When the endometrium measures 12 millimeters, and then we start the progesterone, and before, or at the day of the embryo transfer, this endometrium is between 9 and 12, it is completely fine, it means that the endometrium has compacted.

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Authors

Alejandra Aguilar Crespo, MD

Dr Alejandra Aguilar Crespo is a Gynaecologist and Consultant Specialist at Equipo Juana Crespo, Valencia, Spain. She holds two Master’s Degrees in human reproduction and advanced gynaecological endoscopic surgery. Dr Alejandra Crespo has published several national and international publications in scientific journals and has attended numerous national and international congresses. She speaks English, Spanish and French.

Event Moderator

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.

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