IVF transfer – uterine lining and implantation window

If you are looking for answers to questions above, check the webinar and live Q&A session with Dr Nataliya Kushniruk from FertiCare Prague, in the Czech Republic.

Egg donation is often considered to be the best chance at achieving pregnancy for many patients. As the treatment is time-consuming and expensive, it’s no wonder both patients and doctors recommend taking every precaution possible in order to boost the chances of success. One of the precautions is correctly estimating the implantation window – that is, the period of time during the natural cycle during which the uterus is at its most receptive towards new embryos.

To help us understand just how important the implantation window is – and how exactly it works – we invited Dr Nataliya Kushniruk from FertiCare Prague to share her knowledge and experience. She began her presentation by setting out some basic requirements for egg donation in the Czech Republic – namely, the patient must not be older than 49 years of age on then day of the transfer, must have no contraindications for pregnancy and her BMI must be under 35.

To ensure no complications arise during the pregnancy, prospective mothers undergo detailed testing – from ultrasounds and bloodwork, through mammography’s, to pap smears and hormonal analysis. The results of these tests allow doctors to ascertain whether or not a viable pregnancy can be sustained by the patient. Establishing a general health baseline for the patient mitigates possible complications during the gestation phase of pregnancy.

Partners of patients don’t need to feel left out of the fun – they also should undergo testing. Blood serology, genetic testing, and semen analysis provide information especially important to the fertilisation and implantation processes. In cases of recurrent implantation failure, DNA fragmentation analysis may help reveal the culprit behind the issue.

The general health of the intended father has a real impact on pregnancy; health and lifestyle factors greatly impact the sperm quality, which in turns has an effect on embryo quality and implantation. Couples hoping to find success in IVF should make an effort to improve sperm quality.

Once these tests are concluded and both prospective parents pass, the egg donation process can begin. Dr Kushniruk quickly brought us to speed by explaining egg donation step by step. Following the initial request, a medical coordinator sends a basic questionnaire to the patient interested in egg donation. Once the patient completes it, the first medical consultation can be scheduled. During this consultation, the doctor chooses the best path to proceed based on the patient’s medical history. Additional tests can be scheduled at this point if necessary. After the initial consultation, the clinic sends consent forms to the patients. Once these are signed and once a donor is matched, the egg donation process begins in earnest.

Cycle synchronisation is one of the most important parts of egg donation and it fulfils a twofold role; firstly, it stimulates the growth of follicles within the donor’s ovaries in order to generate more eggs at once. Secondly, it helps grow the recipient’s endometrial lining; this lining is what is ultimately responsible for the endometrium’s receptivity towards embryos. As an added benefit, the embryo transfer can be performed in the same cycle as the oocyte retrieval, requiring only a single visit to the clinic.

The effectiveness of egg donation programmes is dictated by several factors. Embryo quality is one of them and that, in turn, is dictated by the quality of eggs and sperm. In egg donation scenarios, oocyte quality is assumed to be good, as donors are universally young and healthy. Laws and regulations also set out rigorous criteria that potential donors need to match, ensuring that the eggs they provide are healthy and of good quality. Sperm quality, as we discussed, is mostly affected by lifestyle and health factors; in case of male factor infertility, sperm donors can also be used; like egg donors, they undergo screening and must meet certain criteria, which means their sperm is of good quality.

Endometrium quality and receptivity

Endometrium quality and receptivity is another factor. Uterine quality is judged primarily by the thickness of its lining – ideally, it should be over 7.5 millimetres thick at the mid-point of the menstrual cycle. This can be measured through a simple ultrasound. The ultrasound also provides other valuable information about endometrial health – it can be used to defect abnormalities such as polyps, fibroids, myomas, et cetera. Endometrial receptivity is another topic entirely. Two types of receptors inside the uterine cavity are regulated by hormones – oestrogen and progesterone. High enough levels of both hormones signify the endometrium’s readiness to accept an embryo.

Implantation window

This brings us to the implantation window – the most optimal point for embryo transfer. During the implantation window, the uterus presents the best possible environment for the embryo. For most patients, this window occurs between days 19 and 24 of the menstrual cycle. For some patients, this window may be displaced – that is, it could occur earlier or later when compared to the majority of the population. An endometrial biopsy is helpful in determining whether or not that is the case and is a common test ordered for patients suffering from recurrent implantation failure.

– Real patients – woman 44 years old poor responder, husband 46 years old,  primary infertility in addition to adenomyosis

On a closing note, Dr Kushniruk shared with us the story of a couple she treated. The couple were of advanced reproductive age – the wife was 44 years old, while her husband was 46. Their diagnosis was primary infertility in addition to adenomyosis. The woman was also a poor responder – which means she was a patient who did not respond as well as others to hormonal stimulation. Her partner suffered from poor quality of sperm.

At first, the patients attempted three cycles of IVF using their own eggs, which didn’t work. Following that, the couple made a decision to start an egg donation programme. Three fresh egg donation cycles resulted in just one biochemical pregnancy – not a clinical one. The patients didn’t give up however. They had one frozen embryo left from the previous programme. Unfortunately, it still didn’t result in a pregnancy.

After seven unsuccessful cycles, the couple decided to make the switch to donated embryos. Embryos in donation programmes come from other couples who completed their IVF journey and had surplus embryos; when a couple decide they do not want more children, they can donate the embryos to other couples. Alternatively, embryos for donation can be created using egg and sperm donors. In either case, the process results in high quality embryos being available to the patient. Our patients decided to go with the second route.

Embryo donation did not bring immediate effects. The first four cycles resulted in no pregnancy, the fifth resulted in a biochemical pregnancy, while the final – the sixth – resulted in an actual, clinical pregnancy. That’s thirteen attempts in total before a successful pregnancy. So, what went wrong?

An ultrasound of the patient’s uterus revealed that visually, there was no real difference between the endometrium and the myometrium. The patient suffered from adenomyosis – a condition in which endometrial cells grow within the myometrium. Adenomyosis is very tricky to diagnose; a simple ultrasound is often not enough; often, a laparoscopy or a biopsy is required. As a result, her uterus was enlarged and her uterine cavity was not up to the challenge.

However, perseverance paid off; adenomyosis does not mean pregnancy is impossible. By not giving up, these patients eventually achieved their goal and had a healthy child.