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Implantation window and uterine lining in IVF programs with donor eggs #IVFWEBINARS

Are you preparing for an IVF program with donor eggs? We have a webinar for you. How wide is implantation window? What is the ideal endometrial thickness for implantation in IVF programs with donor eggs? What affects uterine lining thickness and how to improve the thickness before the embryo transfer? What if my lining is not improving in thickness? Do I stand a chance?

If you’re looking for answers to these questions, check the webinar and live Q&A session with Dr Nataliya Kushniruk from FertiCare Prague, the Czech Republic. If you missed the webinar live and you have more questions for Dr Nataliya about implantation window or any other topic, contact FertiCare Prague via their clinic profile or get in touch with our International Patients Coordinators at +44 1908 410 693.

Implantation window and uterine lining in IVF programs with donor eggs – Questions & Answers

Question:

Would you recommend DNA fragmentation even if sperm analysis has shown no issues?

Answer:

Sometimes, higher DNA fragmentation percentage may occur even when the semen test comes back as normal, so yes, I would recommend it.

Question:

Would you recommend antibiotics and/or blood flow enhancers to facilitate implantation? No specific implantation issues, but our clinic seems to favour such procedures.

Answer:

 

Let’s start from antibiotics – yes, they will be recommended in case you have some problems with microorganisms or inflammation in the vagina or cervical channel. It would be reasonable to start with a thorough checkup – it would be beneficial to do some extra tests, not just the pap smear that is recommended routinely, but also to take the vaginal culture and to check for Ureaplasma or Chlamydia trachomatis etc. in the cervix. If there is an imbalance in bacteria or bacterial vaginitis, then you should definitely cure it, but even with vaginosis it will be beneficial to normalise the biocenosis in your vagina. Whether you should use antibiotics depends on if the microorganisms present are pathological or semi-pathological, and if they are, then you should take antibiotics. If there are no microorganisms, no inflammation, your leukocytes are within the normal range and your pap smear shows a normal result, then probably antibiotics should not be used.

Question:

What is the role of prednisolone in implantation?

Answer:

We may use these sorts of medicine because when we are talking about the egg donation programme, it means the embryo which is implanted has no genetic links to your organism, and then it might be reasonable to take prednisolone to depress your body’s immune response to it.

Question:

What do you think of the Win-test to find the right implantation window?

Answer:

If you are talking about the ERA test, where we test the estrogen and progesterone receptors in the uterine cavity, it may be helpful to find the implantation window. Sometimes it will be enough to make the transfer one or two days later according to the test result, so your body may be using progesterone for one or two more days, and it may be beneficial. But, it doesn’t mean that only this will help in 100%. The most important thing is to have an individual approach to each patient, and to find what is the cause of implantation failure in each precise case. Sometimes it is enough to simply give one or two days more of progesterone, but in other cases we might have to change something else, or to change the whole protocol. So, each procedure or method may be helpful to some extent


Question:

Would you recommend doing a repeat ERA test after an ectopic pregnancy? First ER mapping was done in November and I will be transferring in June.

Answer:

ERA tests show the concentration of estrogens and progesterone, and the best time for implantation. When we are talking about ectopic pregnancy, if your ERA test was positive, and your implantation occurred at that exact time, then it doesn’t mean that the next time it will lead to ectopic pregnancy as well. An ectopic pregnancy is a possible complication of embryo transfer, and it actually doesn’t relate to the ERA test. If the ERA test showed you that at that precise time, LH peak + 7 days or LH peak + 6 days, then your uterine cavity is ready to accept the embryo – it should be the same in each cycle. So, you probably shouldn’t repeat the ERA test if the first one was positive. If the first ERA test told you your lining was pre-receptive, then please repeat the ERA test until it helps you find the result with receptivity. If the ERA test showed you that you were post-receptive, then definitely the embryo transfer should be done earlier, or if you want to prove that you are on the correct day, then you should repeat the ERA test in the next cycle to ensure that in that particular period, your endometrium is receptive.

Question:

What is your opinion on the ErMap test?

Answer:

As I said previously, every test that we are using is good for some reason. If your doctor has recommended you to take this test, it means by the means of this test, the doctor would like to prove or exclude some kind of pathology, and find the best option for your couple to figure out some problems which may be taking place, and to prepare them in the best way for further IVF attempts. Nobody wants to go through unsuccessful attempts, and the doctors are suffering as well if there is no pregnancy, not only the patients.

Question:

Would you recommend doing an ERA test if I only have 3 day frozen embryos (not blastocysts)?

Answer:

It’s reasonable to do an ERA test to find the best day for the possible implantation. When you have day 3 frozen embryos, you have 2 possibilities. The first is to thaw the embryos and let them grow in the laboratory until day 5 until they become blastocysts – these blastocysts will then be transferred corresponding to the implantation window found in the positive ERA test. If there is no possibility to culture these embryos into blastocysts, then we can presume your embryos will be alive after thawing, and they will develop inside the uterine cavity. We need to make the transfer according to the calculation of when your embryos will reach 120hours, so day 5 (blastocyst stage), and this should be within the implantation window which was found in the ERA test. If both the positive ERA test and the calculated transfer of the day 3 embryos correspond, then this can result in a successful pregnancy.

Question:

What about the Matrice lab test?
Matrice lab test: helps to find if there are Natural Killer cells in the endometrium.

Answer:

In literature, there are several things described. There are articles stating that on the one hand, it may afflict the implantation window, but mostly, in the latest retrospective research, there is data stating that increased numbers of NK cells in the endometrium are linked to recurrent miscarriages. So, the women become pregnant, but these pregnancies may terminate at different stages, but mostly they terminate before 10 weeks of gestation.

Question:

What does it depend on if someone has a triple lining in the cycle or doesn’t have it? Does it mean the endometrium is receptive?

Answer:

Some patients don’t have a triple lined endometrium, and this means that although pregnancy may happen, the percentage of successful pregnancies in this category of patients is much lower in comparison to patients with a normal, trilaminar endometrium.

Question:

I am quite allergic to Utrogestan put inside the uterus and cannot tolerate it orally as it makes me very dizzy/tired. The reaction feels like urticaria (which I have) – continuous itching – I am wondering if this could affect implantation?

Answer:

We have several kinds of progesterone, and definitely, when we are talking about IVF programmes, we need to have good support of the luteal phase. Utrogestan is not the only option to support it. We have several kinds of this medicine, and we have several routes of administration of this progesterone to substitute internal progesterone in your body. If you are allergic to Utrogestan, then you may change it to Crinone gel – this is one option. There is also another medicine, mostly available in the UK, called Cyclogest – it has two routes of administration, either vaginally or rectally, so you may try and use it rectally. Or, we have a good number of intramuscular or subcutaneous progesterones as well, such as Gestone and Gesglutin (intramuscular), or Prolutex (subcutaneous). So, your doctor will select the best option for you, and can definitely substitute Utrogestan. Without the support of the luteal phase with progesterone and without an adequate concentration of progesterone inside the uterine muscle, it’s not possible to imagine a good, progressive pregnancy.

Question:

Do you recommend DHEA during assisted conception procedures and probiotics throughout the procedures?

Answer:

DHEA is recommended in patients who have low concentration of DHEA inside the body. You can use probiotics as well – there are no contraindications for this. If you mean local probiotics, to aid normal biogenesis inside the vagina, it’s reasonable to use them in the stage of preparation and then when you’re at the stage of having the procedure, continue taking the probiotics orally.

Question:

Do you do an endometrial tissue test for micro inflammation and would you use the antibiotic Doxycycline to cure it? What is your opinion on testing the endometrial tissue?

Answer:

You’re talking about the so-called endometrium biopsy, which is an investigation by pathologists, where they look at the sample on a glass slide under the microscope and give us their view on if there is chronic inflammation inside the endometrium or not. If there is a chronic inflammation process inside the uterus, it’s reasonable to use antibiotics, and it should be a broad-spectrum antibiotic. Not only Doxycycline can cure this kind of inflammation. But, to answer your question, yes, it’s reasonable to both check the inflammation and cure it with antibiotics.

Question:

Some studies talk about the positive role of the presence of lactobacillus on the endometrium, cervical cavity and digestive system for implantation success. Can the intended mother take lactobacillus (through diet) to improve successful implantation rates?

Answer:

The uterine cavity should be clear of bacteria. Lactobacillus should be inside the vagina, and yes, it’s good if it is at the correct concentration and balanced. Definitely, you may take lactobacillus or probiotics orally, but the concentration of probiotics is more important in your vagina than in your gut.

Question:

What would you recommend to improve lining thickness?

Answer:

There are several ways that we can improve the endometrium thickness. We can change the concentration of estrogens inside the body – it means that the dose of estrogens should be adjusted. There are several routes of administration of estrogens into your body – it depends on your initial endometrium thickness, and we need to see how it will change. Then, we can try to improve the vascularisation, as it plays a very important role in the development of the endometrium. We can do this by working on the thickness of your blood – there are some medications we can give for better blood flow inside the vessels supplying the endometrium, which can to some extent improve its thickness.  

Question:

I have a history of poor lining. Donor egg blastocyst transfer failed. Lining was 6.7mm. I only have one egg left and I’m worried it won’t work. Was taking 200mg daily of Estradot patches and Fematab. Would you recommend anything before the next transfer?

Answer:

6.7mm – it seems like you may have some previous history of inflammation or some manipulation of your endometrium which has affected its thickness.  However, 6.7mm is not an extremely poor endometrium. It would probably be reasonable to add some medicine that will help the vascularisation process, and even with this, you need to see how it will grow and develop. It is very interesting to see your lining and its thickness in a completely natural cycle, without any type of estrogens. Before the embryo transfer, you could try to do some sort of insignificant uterine injury, to try and change the developmental/reparative process inside your uterine cavity. So, it would be reasonable to think about endometrial scratching if you haven’t done it previously, and to start to adjust the dose of the transdermal patches and oral medications – adding a regional route of administration of medicine may be helpful as well.

However,  not everything depends on the lining. If you had embryos, but failed implantation, then next time, if you decide to go ahead with IVF again, you should check the genetics and full chromosome count of the embryos as well, along with good preparation of your lining. Sometimes, with the type of lining that you have, it may be a good idea to do a number of cycles with estrogen support before you do the transfer of the embryo. You should think about all of this, discuss it with your doctor, and make a decision with how you would like to continue.

Question:

On which day(s) of the cycle should the biopsy testing for chronic inflammation be performed?

Answer:

When we are talking about chronic inflammation, it doesn’t make a difference on which day the biopsy is performed. The best time to do it would be after menstrual bleeding finishes, and then do a hysteroscopy and/or endometrium biopsy in the first part of the menstrual cycle, collecting a sample of the functional layer of the endometrium and also a part of the basal layer, which would show the inflammation.

Question:

If the ERA test shows that I am post-receptive, do I need to repeat the test or is it enough to transfer one day later (one day more of progesterone supplementation)?

Answer:

Post-receptive means that you should do the transfer one day earlier. When you did the ERA test, it means it was done on the same cycle you used for the embryo transfer – the same amounts of estrogens and progesterone, and the same protocol. Now you need to calculate on which day of your menstrual cycle your ERA test was performed. Then you have several options. You could try to transfer the embryo one day before the day on which your previous ERA test was done, or to repeat the ERA test one day earlier than it was previously done. In your case, it will probably be enough to take 4-5 days of progesterone intake before the embryo transfer – it’s very individual. Post-receptive means you put the embryo in when the implantation window was closed, and you have to put it in when it is open.

Question:

Continued from previous question: Sorry, the ERA test showed I was pre-receptive, not post-receptive on the day of the biopsy.

Answer:

Pre-receptive means the opposite of what I said before. It means you need to do the transfer one or two days later than you did before. In my experience, when I had patients who were pre-receptive, it was simply enough to transfer the embryo one day later, and that was it. However, in rare cases, we gave one more day of progesterone and repeated the ERA test and it was still pre-receptive – so, then we would need to give one more day of progesterone. It would be best to repeat the ERA test one day after you did previously and see if it becomes receptive or not.

 

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About the Author

Nataliya Kushniruk

Nataliya Kushniruk

Dr. Nataliya Kushniruk, Physician – Reproductive Medicine and Genetics Specialist at Ferticare Prague, the Czech Republic. Since 2006 Dr. Kushniruk has been working in the assisted reproduction field in various clinics in the Czech Republic. She is a member of the Czech Medical Association, Russian Society for Reproductive Medicine, SHRE, and the Ukrainian Society for Reproductive Medicine. Dr. Nataliya Kushniruk holds the highest category Certificate in Gynecology and Obstetrics, issued in Kiev and is an ISO 9001: 2005 System Management Auditor. Speaks Czech, English, Ukrainian, and Russian.

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