Emakasisese rasedusvastase vahendi paigaldamine 

Vaskne ravivahend mõjutab seemnerakkude ja munaraku liikuvust, vähendades seemnerakkude võimet munarakku viljastada.

Hormonaalne ravivahend muudab emaka limaskesta raseduse jaoks liiga õhukeseks, tihendab emakakaelakanali sekreeti selliselt, et munarakku viljastavate seemnerakkude pääs emakasse on raskendatud. See vähendab ka seemnerakkude liikuvust emakas ja munajuhades, harvem võib ära jääda ka ovulatsioon.

Emakasisene rasestumisvastane vahend sobib naistele, kes soovivad pikaajalist raseduse vältimist. Hormonaalne ravivahend sobib naistele, kellel on vererohke menstruatsioon. Vahendi sobivust hindab naistearst konsultatsiooni käigus.

Ravivahendi paigaldamise eelselt on vaja teha sugulisel teel levivate haiguste uuringud ja onkogünekoloogiline test.

Vahendi paigaldamine on mõnede naiste jaoks valutu, mõnede jaoks ebamugav ja valulik. Vahendi paigaldamiseks on parim aeg menstruatsiooni ajal. Vajadusel kasutatakse paigaldamise ajal valu leevendamiseks lokaalseid valuvaigisteid, näiteks lidokaiinigeeli emakakaelal.

Enne vahendi paigaldamist on vajalik naistearsti konsultatsioon.
Emakasisest vahendit paigaldavad kõik Elite kliiniku naistearstid.

The Glucose Tolerance Test (GTT) is a medical test used to assess how well your body processes sugar (glucose). During pregnancy it is commonly used to diagnose gestational diabetes.

To take the test, you must not eat or drink anything (except water) from the evening before until the test is completed. The test is conducted in the morning at Elite Clinic’s general laboratory.

Upon arrival, a fasting blood glucose level will be measured from a vein sample.

After that, the woman taking the test must drink a glucose solution dissolved in water. The liquid should be consumed within 3–5 minutes.

Blood glucose levels will then be measured from a vein sample one hour and two hours after drinking the glucose solution. During the test, eating or drinking is not allowed; it is recommended to sit or lie down calmly.

The entire procedure takes about 3–4 hours.

Uuringu õnnestumiseks on vajalik loote südamelöökide ja emaka kokkutõmmete salvestamine vähemalt 20 minuti jooksul.

Raseduse ajal teeme uuringut vaid vajaduse korral, sünnituse ajal korduvalt.

KTG uuringusse suunab naistearst.

Rasedusdiabeedi nõustamine

Kui Teil on tuvastatud kõrgem veresuhkru tase ja suunatud glükoosi tolerantsus testile (GTT), siis pärast GDM diagnoosimist, soovitame Teil pöörduda ämmaemanda diabeedinõustamisele.

Ämmaemand selgitab gestatsioonidiabeedi olemust ja selle mõju rasedusele, lapsele ning naise edasisele elule. Õpetab tervislikku toitumist, süsivesikute päevast jaotamist ja füüsilise aktiivsuse positiivset mõju. Annab soovitusi, kuidas pidada toitumispäevikut, kuhu märkida ka veresuhkru väärtused, õpetab glükomeetrit kasutama ja saadud tulemusi mõistma. Enamiku rasedusdiabeediga naiste puhul piisab veresuhkru taseme normaliseerimiseks tervislikust toitumisest ja aktiivsest elustiilist. Raseduse diabeedi ravimise lahutamatu osa on veresuhkru taseme kontrollimine.

Rasedusaegse diabeedi tekke võimalused on suuremad riskigruppi kuuluvatel rasedatel. Haiguse riskitegurid on järgmised:

• Ülekaal (raseduseelne KMI 25-30 kg/m²)
• Gestatsioondiabeet eelneva raseduse ajal
• Diabeet esimese astme sugulastel (ema, isa, õde, vend)
• Anamneesis suurekaaluline (sünnikaal üle 4500g) vastsündinu
• Polütsüstiliste munasarjade sündroom (PCOS)
• Glükosuuria käesoleva raseduse ajal
• Polühüdramnion käesoleva raseduse ajal
• Raseda suur kaaluiive (enam kui 3 kg kuus)
• Raseda vanus üle 40 aasta

Kui Teil on olnud rasedusaegne diabeet, on vaja Teid jälgida ka peale sünnitust. Kuigi veresuhkur normaliseerub 2-7 päeva jooksul pärast sünnitust, haigestub umbes 40% gestatsioonidiabeeti põdenud naistest 10 aasta jooksul insuliinsõltumatusse diabeeti ehk II tüübi diabeeti (suurenenud KMI’ga naistel tõuseb esinemissagedus 50%-ni) . Seetõttu peaksite kuus kuud pärast sünnitust perearsti juures oma veresuhkrut kontrollima ja hiljem tuleks Teie veresuhkrut kontrollida kord aastas.

Medical termination of pregnancy (also known as medication abortion) is a non-surgical method used to end a pregnancy using prescribed medication. It is typically an option during the early weeks of pregnancy.

In Estonia, the termination of pregnancy is regulated by the Termination of Pregnancy and Sterilisation Act, which states that a pregnancy may be terminated solely at the woman’s own request. Termination is permitted if the pregnancy has lasted less than 12 weeks.

A pregnancy lasting more than 12 but less than 22 weeks may be terminated if:

• the pregnancy poses a risk to the woman’s health,
• the child is likely to be born with a severe mental or physical disability,
• the woman’s illness or health condition prevents her from raising the child,
• the woman is under 15 years of age, or
• the woman is over 45 years of age.

A doctor’s appointment is required beforehand, during which the necessary examinations and tests are performed.

Mida loengutes räägime?

Loengutes jagame teaduspõhisusele tuginevaid teoreetilisi teadmisi ja praktilisi nõuandeid, mis aitavad teil kohaneda rasedusega, valmistuda sünnituseks ning beebiga kohtumiseks ja sünnitusjärgses perioodis toimetulekuks. Jagame nõuandeid, toetamaks pere emotsionaalset ja füüsilist heaolu, et saaksite parimal viisil pereks kasvada ning luua pereliikmete vahel head, hoolivad ja armastavad suhted kõikides ees ootavates uue eluga seotud etappides.

Loengute teemad on paindlikud ja saame neid kohandada vastavalt Teie vajadustele.

Loengus saate end mugavalt tunda privaatses ruumis, mis on mõeldud korraga ühele perele. Üks kohtumine kestab 2 akadeemilist tundi ehk 90 minutit. Pange end mugavalt riidesse ning kohtumiseni!

Võimalikud loengute teemad

Rasedus:

• muutused naise kehas, kohanemine
• rasedusaegsed vaevused ja nende leevendamine
• sünnituseks ettevalmistumine nii füüsiliselt kui vaimselt
• partneri sünnituseks ettevalmistamine
• kodu kohandamine beebi sünniks

Sünnitus:

• sünnituse märgid
• mida haiglasse kaasa võtta
• sünnituse kulg, perioodid, lapse sünd
• aktiivsünnitus ja eneseabi, õpime hingama, lõõgastuma, erinevaid
• asendeid (praktiline)
• partneri roll sünnitusel, sünnitaja toetamise võimalused (praktiline)
• valuvaigistamise võimalused
• kui kõik ei lähe plaanipäraselt – eriolukorrad sünnitusel

Sünnitusjärgne aeg:

• varajane sünnitusjärgne aeg haiglas
• sünnitusjärgne periood kodus, selle erilise aja eripärad, kohanemine
• taastumine, vaimse ja füüsilise tervise toetamine
• võimalikud tugiteenused, mida saab kasuta, kellele mõeldud ja millal?
• (sünnitusjärgne koduvisiit, füsioteraapia, raseduskriisi nõustamine jmt)
• pereks kasvamine
• sugueluga alustamine sünnitusjärgselt ja rasestumisvastased vahendid

Rinnaga toitmine:

• imetamiseks ettevalmistumine
• erinevad imetamise asendid, sellega seotud abivahendid (praktiline)
• naise toetus imetamise ajal
• erinevad abivahendid (kuidas valida rinnapumpa, rinnanibukaitset jne)
• alternatiivsed toitmise võimalused (näidistega tutvumine)
• võimalikud rinnaga toitmise raskused ja nendega toimetulek
• imetamisnõustamine, kui beebi on sündinud
• rinnaga toitmise lõpetamine

Beebi:

• esmane hooldus (praktiline)
• beebi vajadused ja nende ära tundmine
• kuidas ma aru saan, et beebil on kõht täis?
• vannitamine (praktiline)
• beebiga õue
• beebi riietamine (praktiline)
• beebi turvalisus
• beebi uni ja päeva rutiin
• beebi arengu toetamine

Teenuseosutajad

Dr. Andrei Sõritsa

Gynecologist and Fertility Specialist

Dr. Deniss Sõritsa

Gynecologist and Fertility Specialist

Artur Minenko

Nutritionist

Dr. Svetlana Räim

Gynecologist and Fertility Specialist

Dr. Julia Orsi

Gynaecologist

Dr. Katrin Org

Gynaecologist

Kaja Julge

Allergy specialist

Tanel Muul

Andrologist-Urologist

Maie Väli

Endocrinologist

Anu Ansip

Gynaecologist

Ülle Kadastik

Gynaecologist

Liis Kriisa

Gynaecologist

Vaalja Kroon

Gynaecologist

Pille Soplepmann

Gynaecologist

Aire Sekavin

Gynaecologist

Karin Truu

Midwife

Jekaterina Kalamees

Midwife

Vahur Ristoja

Ear-Nose-Throat Doctor

Raivo Ani

Ear-Nose-Throat Doctor

Ene Kivirüüt

Ear-Nose-Throat Doctor

Neve Lieberg

Ear-Nose-Throat Doctor

Inga Vaasna

Gynecologic oncologist

Helgi Silm

Dermatologist

Külli Kingo

Dermatologist

Tiit Vaasna

Surgeon

Anu Sööt

Paediatric neurologist

Jaak Lehtsaar

Arno Uppin

Gynecologic oncologist

Teodora Tarkus

Tubakast loobumise nõustaja, Nurse-midwife

Anne Lepasepp

Physiotherapist

Anu Toonverk

Physiotherapist

Hans Jaagup Luuk

Psychiatrist

Lemme Haldre

Clinical psychologist

Mare Riive

Radiologist

Sirje Ress

Anesthesiologist

Liina Korpen

Anesthesiologist

Irina Dmitriev

Anesthesiologist

Eve Int

Anesthesiologist

Ursula Koorits

Anesthesiologist

Anne Vassiljeva

Nurse-midwife

Denis Samarskii

Gynaecologist

I. PREVIOUS INFORMATION FOR PATIENTS

Our personal or family history indicates that there is a risk of transmitting a hereditary condition or severe chromosomal alteration to our offspring.

Therefore, the medical team attending to us has advised us that, in our specific case, one of the medical alternatives to significantly reduce these risks is to include our pre-embryos/embryos1 in the preimplantation genetic diagnosis program.

We have been informed that the risk of such a genetic condition/chromosomal alteration can be reduced by performing genetic analysis on our pre-embryos generated through in vitro fertilization. Additionally, we have been informed about the diagnostic procedures and methods that can be used to analyse the pre-embryos, the chances of success, and the limitations and risks associated with this type of testing.

WHAT DOES PREIMPLANTATION GENETIC TESTING (PGT) INVOLVE?

Preimplantation Genetic Testing (PGT) is a type of genetic analysis conducted on the pre-embryo before its implantation in the uterus. PGT is performed on patients at risk of transmitting chromosomal or genetic abnormalities to their offspring, aiming to improve the selection of only unaffected pre-embryos for transfer to the uterus.

The PGT technique involves the combination of:

• Pre-PGT studies, where applicable.
• In vitro fertilization.
• Biopsy of pre-embryonic cells through micromanipulation.
• Genetic diagnostic techniques using molecular genetics methods.
• Pre-embryo transfer.

II. WHEN IS PGT INDICATED?

This technique is indicated for the detection of pre-embryos carrying serious hereditary diseases, structural or numerical chromosomal abnormalities that could have a significant impact on the quality of life and/or life expectancy of the future newborn, as well as the successful implantation of such pre-embryo.

III. PROCEDURE

A. Pre-PGT Phase (Pre-PGT).

In this phase, genetic characterization tests for the specific genetic alterations to be diagnosed are performed in patients carrying the genetic condition. The aim is to gather maximum information before applying PGT in relevant cases.

B. Obtaining Pre-Embryos.

The objective of this step is to obtain the pre-embryos for analysis. Assisted reproductive techniques, such as in vitro fertilization (IVF), are employed for this purpose. This is necessary even if patients do not have any reproductive abnormalities, as no other method of obtaining pre-embryos is allowed at this early stage of development. In some cases, if there are cryopreserved (vitrified) untested pre-embryos from previous cycles, they may need to be used for analysis. In such cases, the pre-embryos must be thawed (de-vitrified) and their viability confirmed before biopsy.

C. Pre-Embryo Biopsy.

The biopsy is usually performed on the fifth, sixth, or seventh day after fertilization when the pre-embryo is in the blastocyst stage. The embryonic biopsy involves extracting approximately five cells from the trophoectoderm of the pre-embryo. As mentioned earlier, the biopsy can be performed on pre-embryos generated in the current IVF cycle or on cryopreserved pre-embryos from previous cycles. Regardless, once the biopsy is done, the pre-embryos will be vitrified until the analysis results are obtained.

D. Genetic Diagnosis.

The cells obtained from the biopsy will undergo genetic analysis. Depending on the clinical indication, different analysis strategies in PGT may be followed, or even a combination of them. These strategies are briefly explained below:

1. Preimplantation Genetic Diagnosis for Aneuploidies (PGT-A). In patients with an indication to analyse numerical chromosomal abnormalities, the test used will be Preimplantation Genetic Testing for Aneuploidies (PGT-A). This technique allows determining the number of copies of each of the 23 pairs of chromosomes in the pre-embryo samples and identifying both the pre-embryos negative for chromosomal aneuploidy (no alteration in the number of chromosomes) and those positive for aneuploidy (with an alteration in the number of chromosomes) (aneuploids). PGT-A has been shown to detect all whole-chromosome aneuploidies and certain segmental aneuploidies. Additionally, some abnormalities involving a complete set of 23 extra or missing chromosomes (triploidy or haploidy) can be detected. PGT-A will be performed using a method called Next Generation Sequencing (NGS) through the PGTseq platform. The embryonic biopsy will be performed at the blastocyst stage.
   
   In some cases, there may be a need for the combined analysis of a monogenic disease and aneuploidies. In such cases, the blastocyst biopsy will be conducted, and both types of analysis can be performed on the same biopsy sample.
2. Preimplantation Genetic Diagnosis for Structural Chromosomal Abnormalities (PGT-SR). In patients where the indication is a structural chromosomal abnormality, such as chromosomal translocations or inversions, Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) is used to identify pre-embryos that are negative/balanced for the chromosomal segments involved in the rearrangement. The embryonic biopsy will be performed at the blastocyst stage. Similar to PGT-A, PGT-SR will be performed using Next Generation Sequencing (NGS) with the PGTseq platform.
   
   The number of copies of the remaining chromosomes not affected by the structural rearrangement will also be analysed. In other words, in addition to the chromosomes affected by the structural alteration, the rest of the chromosomal set will be examined for the detection of aneuploidies.
3. Preimplantation Genetic Diagnosis for Monogenic Disorders (PGT-M). In patients where the indication is a monogenic disease, Preimplantation Genetic Testing for Monogenic Disorders (PGT-M) is a molecular diagnostic technique that allows the identification of pre-embryos that are genetically normal with respect to the specific variant and gene being analysed. This enables the distinction of pre-embryos that have inherited the genetic alteration associated with the monogenic disease. PGT-M can be performed using the PGTseq-M method or alternatively, Karyomapping along with the study of familial mutations when possible. The embryonic biopsy will be performed at the blastocyst stage. The chromosomal analysis PGT-A is conducted in addition to PGT-M and is intended to reveal embryos that have an incorrect number of chromosomes in their cells.

E. Pre-embryo Transfer.

The medical team at the centre will decide which pre-embryos will be transferred to the patient after considering the chromosomal or genetic makeup and viability of the pre-embryos.

IV. RESULTS

The results of genetic assays and tests should be interpreted in the context of additional laboratory test results, family history, and other clinical findings. Genetic counselling is recommended to analyse the implications of these test results.

Despite the high reliability of PGT, the technique has inherent limitations. Therefore, in any pregnancy obtained after PGT, there is an indication to offer a confirmatory prenatal study as PGT testing should not be considered a substitute for prenatal testing. It is recommended to discuss this point with your maternal-fetal medicine team in the case of an on-going pregnancy.

The overall efficiency of PGT depends on factors such as the number of available pre-embryos, their developmental stage, and the effectiveness of the cytogenetic or molecular diagnostic method used. Furthermore, when PGT is employed to detect a monogenic disease, the final outcome will be influenced by the inheritance pattern of the gene (recessive or dominant) and the number of healthy pre-embryos available at the end of the process.

In general, the average pregnancy rate per embryo transfer in PGT treatments ranges between 50% and 60%. These rates largely depend on the patient’s age, embryo quality, and underlying causes that led to the treatment indication. Different PGT techniques have been used for over 25 years, and no abnormalities associated with their use have been reported in the literature, suggesting that the procedure is safe.

The possible results in PGT-A cases may include:

• Negative: No complete chromosome aneuploidies or segmental abnormalities were detected. This result indicates that no extra or missing complete chromosomes or segmental abnormalities were detected.
• Positive: Complete chromosome aneuploidies and/or segmental abnormalities were detected. This result indicates that at least one complete chromosome is present in excess or is missing, and/or segmental abnormalities were detected.
• No Result: Refers to a failure in DNA amplification or inconclusive results. In these cases, a new biopsy is recommended to obtain another sample for analysis, provided that the pre-embryo quality allows this.

The possible results in PGT-SR cases may include:

• Negative/Balanced: Pre-embryos in which a normal number of chromosomes (46,XX or 46,XY) is predicted, or a balanced chromosomal rearrangement is detected in the biopsy sample (since the technology used does not differentiate between these two states).
• Positive: Pre-embryos in which an abnormal number of chromosomes is predicted in the biopsy sample. These are pre-embryos for which a high risk of chromosomal abnormality has been determined.
• Positive/Unbalanced: Pre-embryo that has inherited the structural chromosomal alteration in an unbalanced state. These pre-embryos show gains and/or losses of chromosomal fragments related to the structural alteration carried by the patient.
• No Result: Refers to a failure in DNA amplification or inconclusive results. In these cases, a new biopsy is recommended to obtain another sample for analysis, provided that the pre-embryo quality allows this.

The possible results in PGT-M cases may include:

• Negative: Pre-embryos that are not expected to have inherited the genetic alteration associated with the monogenic condition. Additionally, no chromosomal abnormalities have been identified.
• Positive: Pre-embryos that are expected to have inherited the genetic alteration associated with the monogenic condition. This category also includes embryos with chromosomal abnormalities.
• Carrier: Pre-embryos that are expected to be healthy carriers of the monogenic disease under study. This applies to autosomal recessive and X-linked recessive diseases. Additionally, no chromosomal abnormalities have been identified.
• No Result: Refers to a failure in DNA amplification or inconclusive results. In these cases, a new biopsy is recommended to obtain another sample for analysis, provided that the pre-embryo quality allows it.
• Non-Informative: The accuracy of the test depends on the results obtained in Karyomapping or PGTseq-M, with or without analysis of the mutation site. If there is a recombination between the mutant gene and the linked polymorphisms, this can also lead to inconclusive results in PGT-M, compromising the accuracy of the test and resulting in the pre-embryo being classified as “non-informative.” The genetic status of a pre-embryo with a “non-informative” status is unknown. In such cases, a second biopsy is not recommended.

V.LIMITATIONS OF PGT. SO-CALLED “NON-INFORMATIVE” PRE-EMBRYOS. INCIDENTAL FINDINGS

Common Limitations of all PGT Tests (PGT-A, PGT-SR, PGT-M)

It is crucial to avoid unprotected sexual intercourse from 15 days prior to egg retrieval until after the pregnancy test, which is performed approximately two weeks after the embryo transfer to the uterus. Sexual intercourse during this time could lead to a natural pregnancy from an untested embryo, invalidating any PGT results.

PGT minimizes the possibility of transferring embryos carrying the chromosomal and/or genetic alteration under study. Like any diagnostic medical technique, there is a margin of error in the test, estimated to be between 1-2% theoretical possibility of diagnostic error in the genetic status of the embryo. Therefore, in any pregnancy obtained after PGT, there is an indication to offer a confirmatory prenatal study as PGT testing should not be considered a substitute for prenatal testing. It is recommended to discuss this point with your maternal-fetal medicine team in the case of an on-going pregnancy. While highly unlikely, there is a possibility that a biopsy sample may be lost or damaged at some point in the clinic, during transport, or in the laboratory. In such cases, a new embryo biopsy will be necessary, provided that the pre-embryo quality allows for this.

Like any other laboratory technique, PGT can be affected by errors that can compromise the obtained result. Common sources of these errors are associated with human errors during sample collection and processing, errors in laboratory equipment and materials, contamination of samples by other cells or external genetic material, or non-compliance with established pre-analytical conditions to ensure the validity of the results obtained.

PGT does not offer any guarantee of achieving a pregnancy or having a healthy child (free from all genetic or non-genetic defects).

Since PGT does not analyse all types of chromosomal or genetic abnormalities, it cannot exclude the possibility that an embryo may have other types of genetic abnormalities and/or birth defects. In the general population, there is a 3-5% risk of a child being born with a birth defect or intellectual disability due to genetic and/or non-genetic causes. The use of PGT does not reduce that risk.

There is a possibility of not obtaining a result from a biopsy sample, which will be classified as “no result.” This can happen if the cells extracted from the embryo contain degraded DNA, as well as due to other technical limitations. This typically affects less than 5% of the samples. If the final result is “no result,” the medical team will advise against transferring the embryos to the uterus. In such cases, a rebiopsy of the embryo may be recommended if its quality allows for it.

PGT results may indicate an intermediate number of chromosomes, also known as “mosaic embryos.” Mosaicism refers to a combination of chromosomally normal and abnormal cells in a single pre-embryo biopsy sample. Embryo biopsies in this category have at least one complete chromosome or a segment of a chromosome falling within the mosaic range. Juno Genetics does not routinely report the presence of mosaicism in a biopsy. According to current scientific evidence, these embryos have the same implantation potential and ability to generate a live newborn as embryos without mosaicism. Therefore, mosaic findings are considered secondary and of uncertain significance. Ultimately, the decision to report mosaic findings will be made by the medical team, who may request Juno Genetics to report mosaic pre-embryos.

In any case, the final clinical recommendation regarding the selection of embryos for transfer to the uterus will be the responsibility of the medical team.

Common Limitations of PGT-A and PGT-SR Tests

This test does not search for any hereditary/genetic or non-genetic conditions within a person’s family history.

In PGTseq-A and PGTseq-SR, all 23 pairs of chromosomes are analysed, and most abnormalities in the number of copies or complete loss of a set of chromosomes (complete haploidy) can be detected. However, certain types of abnormalities cannot be detected, such as some forms of polyploidies (e.g., tetraploidies like 92,XXXX).

Another class of abnormalities that may not be detected are related to losses or duplications of small fragments of chromosomes, known as segmental abnormalities. In general, segmental aneuploidies below 3Mb are not detected. However, the detection limits for segmental aneuploidies vary depending on the chromosome and the quality of the embryonic sample. The probability of a segmental aneuploidy being present in the fetus cannot be predicted.

The detection of uniparental disomies, where both sets of chromosomes come from the same parent instead of one from the father and one from the mother, cannot be guaranteed.

The PGT platform (PGTseq) was validated using embryos generated through Intracytoplasmic Sperm Injection (ICSI). The use of conventional insemination may increase the risk of contamination from maternal or paternal sources. If undetected contamination occurs, it can result in a false negative or false positive.

The PGTseq platform cannot detect all segmental aneuploidies or copy number variants (CNVs). A “Negative” result does not eliminate the risk of a segmental aneuploidy. It is recommended that patients meet with a genetic counsellor and consider the possibility of confirmatory prenatal diagnosis. Most copy number variants (CNVs) identified prenatally and postnatally will not be detected by PGT-A as they are below the detection limit.

Breakpoints of segmental aneuploidies are not precisely determined using PGTseq. The deleted/duplicated chromosome segment may be smaller or larger than indicated in the PGT-A and PGT-SR report. Given this limitation, Juno Genetics does not provide a classification of the clinical significance of segmental aneuploidies.

Occasionally, the results of PGT-A and SR may indicate a chromosomal abnormality of parental origin in one of the couple members, such as a parental chromosomal rearrangement or extra/missing chromosomal material. This type of result is considered an incidental finding. If the results suggest a chromosomal abnormality in the parents, this result will be communicated to the patients. Additional genetic testing may be required in response to such results.

Specific limitations of the PGT-SR Test

While losses and duplications of chromosome fragments can generally be detected within pre-embryos, it is not possible to distinguish pre-embryos that have a balanced form of rearrangement (the same situation as the parent carrying the rearrangement) from those with a completely normal set of chromosomes. This is because in these two situations, the amount of chromosomal material is the same.

The accuracy of PGT-SR depends on the genetic information provided to Juno Genetics in medical records and reports from previously conducted genetic tests. The information provided to Juno Genetics will be evaluated to determine if the PGTseq-SR method could detect unbalanced products derived from the rearrangement. Incorrect definition of chromosomal breakpoints and/or errors in the family history information provided to Juno Genetics may affect the ability of the PGT-SR test to detect unbalanced rearrangement products.

PGTseq-SR will only be able to detect unbalanced products of the specific chromosomal rearrangement within the records provided to Juno Genetics. The accuracy for detecting unbalanced products of the rearrangement is >98%, assuming that the karyotype information provided to Juno Genetics is accurate.

This test reduces, but does not eliminate, the risk of an unbalanced rearrangement in embryos identified as “negative/balanced”.

Specific limitations of the PGT-M Test

The procedures performed for PGT-M focus on the identification of specific inherited genetic disorders, according to the indication for the test. However, the technique used for PGT-M allows for the detection of chromosomal status information of the pre-embryo. This information will be provided to patients whenever available. Chromosomal abnormalities frequently occur in the human pre-embryo and have the potential to cause implantation failure or miscarriage. In any case, the final clinical recommendation regarding the selection of embryos to transfer to the uterus will be the responsibility of the medical team.

This test does not rule out the possibility of other variants in the studied gene, including de novo variants.

The PGT-M test used is specifically designed to analyse the indicated region/gene of interest stated in the test request. Other additional genes/regions will not be studied.

The accuracy of PGT-M for the detection of a disorder caused by a mutation in a single gene is estimated to be at least 95%, depending on the methodology used. However, it is important to note that the risk of an affected child/pregnancy after transferring a pre-embryo predicted to be “normal” or “carrier” is not zero. The intention of the test is not to guarantee an unaffected pregnancy or delivery, but to reduce the risk of transferring an affected pre-embryo to the uterus. Despite the high reliability of PGT-M test, there are inherent limitations to the technique. Therefore, there is an indication to offer a confirmatory prenatal study as PGT testing should not be considered a substitute for prenatal testing. It is recommended to discuss this point with your maternal-fetal medicine team in the case of an on-going pregnancy.

The use of intracytoplasmic sperm injection (ICSI) as a fertilization method is highly recommended for PGT-M cases, as it helps reduce the risk of DNA contamination caused by sperm. If contamination is present but goes undetected, a misdiagnosis can occur.

VI.ALTERNATIVES TO THE PGT TECHNIQUE

• Natural conception followed by prenatal diagnosis, provided that the couple is willing to consider voluntary termination of pregnancy if fetal abnormalities are detected.
• Use of donor gametes (eggs or sperm) from a non-affected individual, depending on who is the carrier of the disease.
• Legal adoption.

Plasma rich in growth factors (PRGF) is a liquid prepared from a sample of the patient’s own blood.

This PRGF is prepared according to the PRGF-Endoret® closed-technique system developed by BTI Biotechnology, and is a biomedical technology aimed at stimulating tissue regeneration through the application of growth factors and other proteins present in blood plasma. The application of Endoret® Technology (PRGF®) is a medicinal product for human use.

Platelet growth factors are a set of proteins that are involved in cell communication by modifying biological responses. These types of therapies have been widely used in many fields of medicine and dentistry and are based on Regenerative Medicine, and they aim to achieve tissue regeneration by mimicking the body’s own regeneration processes.

Suitability of the treatment in relation to its application in the endometrium

Refractory endometrium is a condition in which the endometrium, the innermost layer of the uterus where the embryo implants, does not grow properly despite appropriate hormonal treatment. If the endometrium does not grow properly, communication between the endometrium and the pre-embryo is not established, resulting in the pre-embryo not growing properly. Refractory endometrium is diagnosed by ultrasound measurement of the endometrium. It should be at least 6 to 7 mm after 10 days of hormone replacement therapy with oestrogen. Scientific studies have shown that PRGF promotes endometrial growth and is effective in repairing a damaged endometrium and improving pregnancy outcomes, hence its recommendation.

Treatment alternatives

Refractory endometrium is a difficult pathology to manage and with few effective alternatives currently described (vitamin E, vaginal sildenafil citrate and pentoxifylline), none of which have sufficient scientific evidence to be considered a form of treatment of choice.

Procedure

• After 10 days of hormone replacement therapy, if the endometrium does not grow adequately, a blood sample is taken from the patient.
• This blood sample will be prepared in a Endoret® closed system.
• There are two modes of administration:
  • As an outpatient with endometrial instillation
  • It is separated into three parts.
  • One for fresh instillation and two others that are frozen for subsequent instillation into the endometrium (at 48 and 96 hours after the fresh instillation).
  • Endometrial instillation is a simple and painless procedure performed at the doctor’s office or in the embryo transfer room through the vagina.
  • A vaginal speculum is inserted and the cervix is cannulated with an embryo transfer cannula.
• With hysteroscopy and subendometrial injections:
  • Single preparation
  • The endometrium is injected by depositing PRGF at the subendometrial level with small injections a few millimetres deep. This procedure is always accompanied by a diagnostic hysteroscopy that allows us to see the exact site of the injection and its depth, for which the corresponding informed consent for diagnostic hysteroscopy must be signed. The choice of mode of endometrial administration of PRGF will depend on a shared medical decision between you and your doctor.  The idea with subendometrial injection is to inject the factors at the level of the stem or progenitor cells and have more influence on cell growth and vascularisation. This approach has demonstrated histological changes related to endometrial regeneration.
• After the procedure the patient can return to normal life.

Contraindications

There are certain conditions in which it is not advisable to perform endometrial instillation due to a possible risk of encouraging or worsening other pathologies:

• Current or previous pelvic inflammatory disease.
• Infection.
• Active genital infection.
• Presence of any pathology that in the medical specialist’s opinion constitutes a risk or contraindication for the patient.
• Patients with reports from specialists advising against pregnancy.
• Positive serologies for the tests performed according to standard clinical practice in the IVIRMA group in Spain (HBsAg, HBcAb, HCV, HIV and syphilis).

Risks

This instillation is autologous, i.e., it comes from the patient’s own blood, so the patient is not exposed to foreign cellular material that could cause a reaction in her body.

In addition, the system used is closed, so we do not expect any contamination.

No risks or side effects are described in the literature with this procedure.

Although there is a theoretical risk of infection from introducing material into the endometrial cavity from the outside and through the vagina, this is the same risk that could occur in an intrauterine insemination or embryo transfer, which is practically zero in the thousands of these procedures performed, and prophylactic antibiotics are administered to prevent infection.

Although no long-term complications have been reported, it is possible that due to the pathogenesis of endometriosis and adenomyosis, microtrauma at the subendometrial level could favour the development of these pathologies.

Service Providers

Dr. Andrei Sõritsa

Gynecologist and Fertility Specialist

Dr. Deniss Sõritsa

Gynecologist and Fertility Specialist

Dr. Svetlana Räim

Gynecologist and Fertility Specialist

Plasma Rich in Growth Factors (PRGF-ENDORET®) for Ovaries

Plasma rich in growth factors (hereinafter also PRGF) is a preparation from a sample of the patient’s own blood.

This PRGF is prepared according to the PRGF-Endoret® closed-technique system developed by BTI Biotechnology, and is a biomedical technology aimed at stimulating tissue regeneration through the application of growth factors and other proteins present in blood plasma. The application of Endoret® Technology (PRGF®) is a Medicinal Product for Human.

Platelet growth factors are a set of proteins that are involved in cell communication by modifying biological responses. This type of therapy has been widely used in many fields of medicine and dentistry and is based on Regenerative Medicine; it aims to achieve tissue regeneration by mimicking the body’s own regeneration processes.

Suitability of the treatment in relation to ovarian ageing

Ovarian ageing is a term that describes a wide range of pathophysiological conditions in which ovarian function is compromised. In the context of assisted reproductive treatment, women with severely diminished ovarian reserve may have a poor response to ovarian stimulation treatments, recovering very few oocytes or those recovered being of poor quality.

Considering that success in these treatments depends on having good quality pre-embryos, the reproductive potential of these patients is quite limited.

Therefore, in Reproductive Medicine, intraovarian administration of an activated plasma rich in growth factors is a novel approach that has shown promising results in the context of regenerative medicine, hence it being recommended to improve certain gestation possibilities. At this time, studies have already been published in which restoration of ovarian function has been observed through the administration of this platelet concentrate, with the resulting improvement in the results derived from assisted reproduction treatment, hence its recommendation.

Alternatives to treatment with intraovarian administration of plasma rich in growth factors

Ovarian ageing is a physiological process associated with a decrease in oocyte quantity and quality that has critical implications for fertility and is a major reason in seeking solutions based on assisted reproductive techniques. The wide range of factors that can affect ovarian function, from advanced maternal age to genetic and/or environmental factors, can add a further level of complexity, making efficient management of this characteristic difficult to achieve.

The options currently available include very specific assisted reproduction strategies with own oocytes, which have mixed results. If no results are obtained, gamete donation treatment alternatives and/or adoption can always be used as a last resort.

Procedure

• Firstly, compliance with the inclusion criteria is required for the possibility of undergoing this treatment.
• The blood sample will be processed according to the protocol of the closed-system PRGF-Endoret®.
• Administration of a predetermined volume (ml) of activated plasma rich in growth factors transvaginally, under ultrasound guidance and sedation.
• After the procedure, the patient will remain under observation for 30-40 minutes and she will be discharged on an outpatient basis.
• After the procedure the patient can return to normal life.

Contraindications

There are certain conditions in which it is not advisable to perform intraovarian administration of PRGF due to a possible risk of encouraging or worsening other pathologies:

• Genetic ovarian insufficiency.
• History of malignant ovarian tumour.
• Presence of any pathology that in the medical specialist’s opinion constitutes a risk or contraindication for the patient.
• Patients with reports from specialists advising against pregnancy.

It is important that you inform your doctor of all your medical conditions and any drugs you are taking.

Risks

This instillation is autologous, i.e. it comes from the patient’s own blood, so the patient is not exposed to foreign cellular material that could cause a reaction in her body.

The risks are similar to those of an ovarian puncture as both involve sedation and an oocyte puncture under transvaginal ultrasound guidance; the only difference is that instead of extracting oocyte fluid, a platelet concentrate will be injected. Risks associated with this procedure similar to ovarian puncture include haemorrhage, pelvic organ injury (bladder, bowel or blood vessels, pelvic infection and ovarian torsion).

The risk of complications may be increased in cases of previous abdominal surgery with pelvic adhesions, autoimmune, infectious or endocrine diseases. In all these situations, the medical team will establish the risk/benefit of the procedure and give appropriate recommendations.

In the event that the needle punctures skin and/or mucous membranes, there is a theoretical risk of infection and/or bleeding, but these risks are minimal. Since the procedure is performed under sedation, you will not experience any pain. After the procedure, you will remain under observation for 30-40 minutes when you will be discharged on an outpatient basis.

In addition, the system used is closed, so we do not expect any contamination.

No risks or side effects are described in the literature with this procedure.

Assisted hatching is a microscopic technique that facilitates the breakage of the embryo’s protective membrane. We cut the embryo membrane with a laser just before transfer to the uterus.

This technique increases the chances of getting pregnant in case of abnormalities of the embryo membrane (zona pellucida).

What Is Assisted Hatching?

During IVF treatment, fertilization takes place in the lab. But as any couple that has gone through an IVF treatment knows, having a fertilized embryo does not guarantee a pregnancy. The embryo transferred has to implant itself into the endometrium and “stick” for pregnancy to occur.

Up to 85 percent of embryos transferred do not “stick.” There are theories on why this occurs, and one of those theories is that the embryo doesn’t hatch properly. This may happen because the embryo intrinsically has an unusually hard shell, or because something in the lab environment (the cultures used to keep the embryo alive, cryopreservation chemicals, etc.) has artificially interrupted the hatching process.

Assisted hatching is meant to get over whatever hurdles are preventing hatching and improve the odds of implantation (and pregnancy) success.

Laser-assisted hatching: Using a specialized laser to breach the zona pellucida is another possibility. Laser-assisted hatching allows much more control of the size of the hole created. Of all the methods, laser-assisted hatching may be the safest and most effective.

Does Assisted Hatching Improve IVF Success Rates?

The big question is, of course, is it worth it? Does assisted hatching to help you take home a baby? The answer is a bit complicated.

A Cochrane review on assisted hatching—that considered 31 studies, totaling 1,992 pregnancies and 5,728 women—found that assisted hatching just slightly improved clinical pregnancy rates. However, live birth rates did not improve.

Live birth rates are more important to consider than the clinical pregnancy rate since the goal in any fertility treatment is taking home a baby – not just getting a positive pregnancy test.

Unfortunately, most of the research on assisted hatching has only reported clinical pregnancy rates, and not live birth rates. Those that did look at live birth rates didn’t find an advantage. More research must be done.

Another study found that when assisted hatching was done on “good quality” embryos, pregnancy rates went down. The results varied depending on age group when assisted hatching was done on fair to poor quality embryos. This would imply that assisted hatching not only won’t help those with a good prognosis, but it may harm their chances of success.

Who Might Benefit From Assisted Hatching?

There is evidence that assisted hatching may improve clinical pregnancy rates with patients who:

• Have experienced two or more failed IVF cycles
• Have poor embryo quality
• Are older than age 38

Risks

Any manipulation or interference with an embryo is going to involve some risk. One possible risk to assisted hatching is that the embryo will become lethally damaged. This could occur before embryo transfer or after. In either case, pregnancy would not result.

Somewhat ironically, another risk of assisted hatching is the embryo’s natural hatching process will be thrown off and the embryo will fail to fully hatch from the zona pellucida.

Another risk of assisted hatching is twinning, specifically monozygotic twinning. Monozygotic twins are identical twins, who come from one egg and one sperm. Twinning is already increased during conventional IVF treatment, and research has found that assisted hatching my further increase that risk. While all multiple pregnancies carry risk, monozygotic twin pregnancies come with even higher risks for the mother and babies. Still, the risk of twinning is low, occurring less than 1 percent of the time.

You may be wondering if assisted hatching increases the risk of birth defects. A large retrospective study of over approximately 35,000 cycles found that the risk of congenital anomalies was not significantly increased with embryos that were manipulated with assisted hatching, compared to IVF cycles where assisted hatching did not take place.

Written by Rachel Gurevich

Article sources

• Carney SK1, Das S, Blake D, Farquhar C, Seif MM, Nelson L. “Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI).” Cochrane Database Syst Rev. 2012 Dec 12;12:CD001894. doi: 10.1002/14651858.CD001894.pub5. https://doi.org/10.1002/14651858.CD001894.pub5
• Hammadeh ME1, Fischer-Hammadeh C, Ali KR. “Assisted hatching in assisted reproduction: a state of the art.” J Assist Reprod Genet. 2011 Feb;28(2):119-28. doi: 10.1007/s10815-010-9495-3. Epub 2010 Nov 2.
• Jwa J1, Jwa SC2, Kuwahara A3, Yoshida A4, Saito H5. “Risk of major congenital anomalies after assisted hatching: analysis of three-year data from the national assisted reproduction registry in Japan.” Fertil Steril. 2015 Jul;104(1):71-8. doi: 10.1016/j.fertnstert.2015.03.029. Epub 2015 Apr 29.
• Knudtson JF1, Failor CM2, Gelfond JA3, Goros MW3, Chang TA2, Schenken RS2, Robinson RD2. “Assisted hatching and live births in first-cycle frozen embryo transfers.” Fertil Steril. 2017 Oct;108(4):628-634. doi: 10.1016/j.fertnstert.2017.07.011. Epub 2017 Aug 30.
• T.A. Chang, J.F. Knudtson, Y.T. Su, E.S. Jacoby, R.D. Robinson, R.S. Schenken. “Efficacy of assisted hatching based on embryo quality in IVF cycles with fresh transfers.” Fertility and Sterility. September 2016,Volume 106, Issue 3, Supplement, Page e314.

Elite Clinic offers a DNA test prior to pregnancy which prevents genetic disorders in the baby.

The Carrier Screening Test or Carrier Genetic Test (CGT) is an important genetic test when planning a family, because it helps to determine the risk of having a child with a genetic disease. This test tells us whether the parents carry one or more known recessive genetic mutations. Carriers are usually healthy but when two parents carry a mutation in the same gene they might produce an affected child. Anyone, without knowing, can be a carrier of one or more mutations. The Carrier Screening Test allows us to know which genes are altered in each person.

The procedure is carried out through a simple blood analysis.

Why do a Carrier Screening Test?

Generally, parents only realize they are carriers of serious genetic disorders after an affected child is born. Genetic disorders can’t be cured, but they can be prevented. It is the only clinically validated test.

Who is the Carrier Screening Test for?

We all have changes in our genes and the carrier screening test allows us to find out whether they could cause a disease in our children.

The test is recommended in the following cases:

• Before attempting a pregnancy by natural means:
  for any woman who wants to become pregnant in order to know the risk of transmitting possible disorders to her children.
• Before an assisted reproduction treatment:
  it is advisable to find out the risk of transmission and to be able to determine the best type of treatment in each case.
• Before treatment with donor sperm or eggs:
  In order to be able to select a donor that doesn’t carry the same mutation as the member of the couple who will provide the gametes (eggs or sperm).

The CGTPlus test and the CGT Exome test can also be used in donation programs.
Gynecologist consultation is added to the price.

Modern medicine has done much to offer more and more additional possibilities of genetic testing but they are rather expensive and do not give absolute information which kind of diseases will affect the future child, testing provides only the information about tested genes and their related diseases.

It helps to determine the risk of having a child with a genetic disease. This test tells us whether the parents carry one or more recessive genetic mutation. Carriers are usually healthy but when two parents carry a mutation in the same gene they might produce an affected child. Anyone, without knowing, can be a carrier of one or more mutations.

Most people today don’t use genetic matching and main reason for that is a high cost. At least you must know about this possibility.

Additional information

1. The test result takes up to 4 weeks. If you would like to perform the test, we can start with program after getting the result.
2. Every man and every women has changes in their genes. If both a man and a woman have the same mutation the child might have a genetic disease. The result informes us about a risk, the results is not an absolute fact that a child will be affected. The global prevalence of all single gene diseases at birth is approximately 10/1000 : WHO-Genes and human diseases
3. With the help of this test we can control only a part of the most common genetic diseases that occur more often, we cannot control and have information about all genetic diseases.
4. According to scientific investigations maybe about 8% of donors are incompatible with your husband.
5. All donors according to Estonian law are tested for karyotype, Cystic fibrosis and Fragile X chromosome. Our donors are investigated by a psychologist. This is a standard that is usually practised in IVF centres testing the donors in Europe.
6. Each person has more than 100,000 genes. We do not test them, we don’t have enough knowledge about this complicated system.
   Risk for genetics diseases is rather small but still exists as everyone has gene defects. And an additional testing could give additional information about the risks.

Service Providers:

Dr. Andrei Sõritsa

Gynecologist and Fertility Specialist

Dr. Deniss Sõritsa

Gynecologist and Fertility Specialist

Dr. Svetlana Räim

Gynecologist and Fertility Specialist