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In vitro programmes after failures 2017-01-27T10:01:24+00:00

Reasons for failures of in vitro fertilisation programmes

…a failure of an in vitro programme is not a complete failure!
It is a chance of more successful treatment…

Patients after a failure of in vitro fertilisation are a special group.

Although information on lack of pregnancy is an emotional burden, data obtained during therapy may be significant for further management. If they are used appropriately, they allow to modify treatment and to increase chances of pregnancy during the next attempt.

We use an individual approach to each couple with a failure of in vitro fertilisation in the past. We offer a personalised set of expanded tests and additional specialist consultations, if necessary. Based on the analysis performed by a medical team, we prepare an alternative approach based on the most current knowledge, experience of many years and the latest diagnostic tests and therapeutic approaches.

Statistics regarding patients who were admitted to INVICTA Clinics from other centres, also international ones:

Abnormal response to stimulation 18%
Low quality of oocytes 14%
Decreased semen 35%
Abnormal embryo development 29%
Impaired embryo implantation 37%
Pregnancy loss / Miscarriages 42%
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18%

% patients who may have this problem

Abnormal response to stimulation

Based on the results of research studies, when controlled hormone stimulation of the ovaries is planned based on the ovarian reserve assessment (AMH), it significantly increases a chance of an appropriate response of the patient’s body to medications. When results of AMH and additional tests during hormone therapy are not included, the efficacy may be affected.

The following factors may also be significant in case of failures at the stage of a response to stimulation: selection of a stimulation type, day when treatment was started, presence of an early dominant follicle in the ovary (its activity may inhibit growth of other follicles).

In some patients, a response to stimulation is too poor despite appropriate levels of AMH (approximately 20% of cases, so-called hyporesponders). Abnormalities may also be associated with genes – they may result from polymorphisms or mutations in the genes for hormones such as LH, FSH, oestradiol and other hormones and their receptors.

An abnormal response to stimulation may result in the following, among others: lack of oocytes for collection, obtaining immature cells, hyperstimulation syndrome.

Possible management:

modified management of stimulation taking individual patient’s needs into account, use of additional pharmacotherapy, genetic diagnostic tests for polymorphisms of respective genes that may affect therapy

14%

% patients who may have this problem

Low quality of collected oocytes

The quality of oocytes is the most significantly affected by the woman’s age as well as their level of ovarian reserve (the older the patient is, the lower AMH levels are, and the lower cell capacity for fertilisation and normal division). At the same time, impaired gamete quality may be a result of deficiencies of various substances such as DHEA, growth hormone, testosterone. It may also be associated with abnormal functioning of proteasomes (responsible for degradation of unnecessary particles inside a cell).

A low quality of oocytes signifies a poorer prognosis with regard to successful fertilisation and normal embryo development.

Possible management:

in case of deficiencies – appropriate, individualised supplementation based on the patients’ test results; in case of an increased genetic risk – specialist consultations, parents’ tests, PGS/PGD preimplantation diagnosis, in vitro programme with oocytes from a donor.

35%

% patients who may have this problem

Decreased semen quality

The quality of the partner’s semen may be one of the reasons for failures of in vitro fertilisation programmes.

Despite normal basic parameters, male genetic material disturbances or sperm immaturity may result in lack of fertilisation or inhibition of embryo development. Expanded diagnostic tests are recommended when male factors are suspected.

Possible management:

consultation with an andrologist, tests, such as, among others, sperm DNA fragmentation, sperm morphology analysis under magnification (MSOME), hypoosmotic swelling test (HOS), expanded semen analysis SOME+HOS and sperm-hyaluronan-binding assay. Appropriate diagnostic tests are recommended by a physician based on indications, andrologic treatment, testicle biopsy, procedures in an in vitro laboratory – such as sperm separation, FAMSI, IMSI-MSOME.

9%

% patients who may have this problem

Morphology of oocytes is normal but there is no fertilisation

Gamete interaction is a complex reaction involving many factors and mechanisms. The intracellular calcium levels are elevated in a mature, normal sperm. Prior to fertilisation of an oocyte, a sperm has to be able to bind to and penetrate the zona pellucida.

As a result of gamete fusion, a sperm introduces a factor activating the oocyte into the cell: phospholipase C zeta (PLC zeta) that is responsible for the formation of appropriate levels of free calcium ions inside the oocyte. These levels are responsible for activation of an oocyte and allow for subsequent cell divisions and embryo development. However, sometimes this mechanism fails.

In case of couples who receive in vitro treatment, it is possible to observe a low rate of fertilised oocytes (below 30%) or complete lack of such cells.

Possible management:

oocyte activation using calcium ionophores; this method may increase the fertilisation rate even by 40%. At the same time, it is safe for further embryo development. Expanded diagnostic tests for male factors. Techniques supporting selecting an appropriate sperm at an in vitro laboratory (IMSI-MSOME, FAMSI).

29%

% patients who may have this problem

Inhibition or significant impairment of embryo development

During the first days after fertilisation, embryos are provided with optimum conditions for growth and their progress is carefully monitored by embryologists.

Impaired division at this stage, inhibited development or severe abnormalities in this process usually have genetic background. In such situations, it is recommended to perform complex tests of future parents and to plan treatment based on information achieved.

Possible management:

Genetic testing of future parents, genetic consultation, PGS/PGD preimplantation genetic diagnosis.

37%

% couples who may have this problem

Implantation disturbances
– RIF (Repeated Implantation Failure)

Failures at the stage of implantation may result from abnormal development of embryos or problems with the endometrium/uterus.

The woman’s age, her ovarian reserve, presence of genetic mutations and an increased rate of partner’s sperm DNA fragmentation; all these factors may increase the risk of genetic abnormalities and result in embryo death, even prior to its implantation into the uterine wall.

Impaired implantation may result from the presence of polyps or abnormal endometrial growth, changes in the uterus (myomas, adhesions) or an abnormal uterine structure.

In few cases, failures after transfer may be a result of immune factors. A reason for failures should be verified by expanded diagnostic tests.

Possible management:

in case of genetic factors – preimplantation diagnosis; in case of disturbed endometrial function – appropriate pharmacotherapy; or minimally invasive surgeries in case of lesions in the uterus. Sperm DNA fragmentation test. Immunological tests.

43%

% couples who may have this problem

Recurrent miscarriages and pregnancy loss
– RM (Recurrent Miscarriages), RPL (Recurrent Pregnancy Loss)

Recurrent (at least 2) pregnancy loss or miscarriages at an early stage observed for the same couple may have various reasons – including endocrine factors, but also genetic, immune or anatomic factors.

Therefore, patients experiencing such problems require expanded diagnostic tests and counselling provided by a team of specialists from various fields. It is also recommended to provide appropriate psychological support, such as Tender Loving Care (TLC).

Contrary to common knowledge, stress and emotional status of a patient may affect her chances of sustaining pregnancy.

Possible management:

depending on reasons of failures that have been diagnosed – depending on the causes of this problem (starting from medications, supplements, small procedures and ending with embryo genetic testing – PGS/PGD diagnosis)

Reasons for infertility among patients undertaking an in vitro programme

Source: cda.gov (2006) http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5805a1.htm

The most common reasons for infertility that have been diagnosed in the American population – according to SART – Society for Assisted Reproductive Technology. Data were prepared for a group of patients who undertook a programme of in vitro fertilisation. Reduced ovarian reserve and male factors are two most common reasons for infertility. The INVICTA Clinic has been conducting research studies for many years, and, as a result, it has good efficacy among couples with reduced AMH and with male factors. Consequently, at our Clinics, we can use latest diagnostic tests and procedures every day.

Cancelled in vitro cycles at the stage of oocyte collection or embryo transfer

Source: SART-  http://www.sart.org/ (2014 r.)

The chart presents percentage of interrupted in vitro cycles due to lack of oocytes for collection and lack of embryos for transfer – according to SART – Society for Assisted Reproductive Technology. Lack of cells for collection means that it was not possible to collect oocytes from a patient for some reasons (e.g. reduced ovarian reserve, inappropriately scheduled stimulation protocol). In case of lack of embryos for transfer – despite oocyte collection – it was not possible to fertilise oocytes or cells had been fertilised but embryo development was abnormal.

Aneuploidies in embryos and the woman’s age

Source: SART-  http://www.sart.org/

The chart presents a correlation between the woman’s age and presence of chromosomal aneuploidies in embryos – according to SART – Society for Assisted Reproductive Technology. Data were prepared for a group of patients who undertook a programme of in vitro fertilisation – a biopsy of embryos was performed at the blastocyst stage. It can be easily observed that genetic abnormalities in embryos are also common (approximately 31.7%) in women younger than 35 years. They may lead to failed implantation, miscarriages or pregnancy loss. INVICTA Clinics have been performing tests for chromosomal aneuploidies in embryos since 2005 – since 2013, we have been using the latest technique: NGS (Next Generation Sequencing) that provides the greatest possible accuracy of reading genetic material.

Miscarriages and the woman’s age

Source: SART-  http://www.sart.org/

The chart presents a correlation between the woman’s age and miscarriages in a given group – according to SART – Society for Assisted Reproductive Technology. Data were prepared for a group of patients who undertook a programme of in vitro fertilisation. The mean for patients older than 35 years is 33.7%. Miscarriages may have a genetic background – presence of chromosomal aneuploidies in embryos. INVICTA Clinics are dedicated to management of patients who have experienced miscarriages and pregnancy loss. Thanks to PGS-NGS 360 embryo genetic diagnostic tests, we achieve very good results – the efficacy above 70% – confirmed by international publications in this field.

Consultation after a failure at INVICTA Clinics

Since 2000, INVICTA Clinics have been dedicated to the most difficult cases. People who have experienced failures of in vitro programmes constitute a large number of our patients.

We have been supporting couples not only from other Polish centres but also from centres in the United Kingdom, Scandinavian countries, Australia, USA, Canada or Russia.

Every day, a dedicated team of experienced INVICTA specialists manages cases of patients in whom previous attempts of in vitro treatment failed. Our approach is based on expanded diagnostic tests (our tests are performed at our own Medical Laboratories), comprehensive know-how and current research reports.

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Consultation at INVICTA after a failure of an IVF programme – step by step

  • Preparation of documentation:
    results of previous laboratory tests (from each stage of treatment – qualification, diagnosis during and after an IVF programme), embryological discharge abstract (summary of procedures and observations from an in vitro laboratory), discharge abstracts after procedures (pick-up and transfer), hospital discharge abstracts, medical history and medical interview are valuable sources of important information; we recommend to prepare this documentation in advance.
  • Review of documentation by a physician
    In order to make it possible for a physician to use time during a consultation to the maximum, they should be able to have access to almost complete patient’s documentation prior to a face-to-face meeting. In such a case, a physician may be better prepared for a consultation and may provide a couple with a more detailed diagnosis.
  • Consultation visit
    During a visit with a specialist, factors that might have affected a failure during previous treatment will be discussed and any possible diagnostic tests will be ordered, if necessary. Sometimes as early as at this stage, a physician may be able to suggest specific measures that might be taken in the future to increase chances of pregnancy.
  • Medical team consultation
    When all necessary information has been collected, a patients’ situation is analysed by a medical team, paying special attention to:
    – Possible reasons for a failure
    – Possible strategies of diagnostic and/or medical management
    – Treatment plan – prepared by a physician after a medical team consultation
  • Wizyta poświęcona planowi leczenia
    Omówienie kolejnych kroków, propozycji modyfikacji terapii i rokowań przy kolejnym programie.
SEE WHAT A CONSULTATION LOOKS LIKE

Important things to know

Tests that should be considered in case of a failure of an in vitro programme:

  • Another assessment of the ovarian reserve (AMH with levels of Inhibin B + assessment of the number of antral follicles)
  • A full set of hormone tests for both partners
  • Expanded semen tests, including morphological assessment, sperm DNA fragmentation test
  • Karyotype of both partners (assessment of the risk of genetic abnormalities) and possibly additional genetic tests for single-gene diseases
  • Genetic tests of partners – including factor V Leiden, mutations in the prothrombin gene, AZF (azoospermia factor), polymorphisms and mutations in the genes of hormones (as above) and their receptors
  • Detailed imaging diagnostic tests, including ultrasound examinations, fertiloscopy, hysteroscopy
  • Possible immunological tests – after a consultation with a physician, according to indications
  • Possible tests for deficiencies of vitamins and other substances – including growth hormone, vitamin D, DHEA, testosterone – after a consultation with a physician, according to indications
  • Possible specialist consultations regarding genetics, endocrinology, immunology, gynaecological surgery etc.

When diagnosing reasons for failures of in vitro fertilisation programmes at INVICTA Clinics, particular attention is paid to the following:

  • Analysis of previous in vitro fertilisation programmes and medical procedures performed at that time
  • Detailed hormone diagnostic tests of both partners
  • Assessment of the anatomy of the uterus
  • Assessment of possible endometrial dysfunctions
  • Analysis of the effects of immune factors
  • Diagnostic tests for genetic abnormalities – associated with both woman and man
  • Patients’ emotional support
  • Analysis of rare causes – congenital and acquired disturbances of the clotting parameters, inflammation

INVICTA Fertility Clinic Gdańsk

  • Andrzej Hajdusianek MD
    Andrzej Hajdusianek MD
  • Prof. Krzysztof Łukaszuk PhD, MD
    Prof. Krzysztof Łukaszuk PhD, MD
  • Adam Stencel MD
    Adam Stencel MD
  • Piotr Głodek MD
    Piotr Głodek MD

INVICTA Fertility Clinic Warsaw

  • Andrzej Jeżak MD
    Andrzej Jeżak MD
  • Michał Kunicki PhD, MD
    Michał Kunicki PhD, MD
  • Janusz Pałaszewski MD
    Janusz Pałaszewski MD

INVICTA Fertility Clinic Wroclaw

  • Mirosław Jakubów MD
    Mirosław Jakubów MD

Our Clinics

INVICTA Gdańsk, ul. Rajska 10

INVICTA Gdańsk
ul. Rajska 10

INVICTA Warszawa
ul. Złota 6

INVICTA Wrocław
ul. Grabiszyńska 208

INVICTA Gdynia
ul. Władysława IV 50/3

INVICTA Słupsk
ul. Frąckowskiego 15

Andrzej Hajdusianek MD
Specialist in obstetrics and gynecology.
Prof. Krzysztof Łukaszuk PhD, MD
Medical Director of INVICTA Fertility Clinics.

Medical Director of INVICTA Fertility Clinics. Second degree specialist in obstetrics and gynecology. Member of Polish and foreign scientific societies, including the PTG, PTMR, PTDL, PTA, PGDIS, ESHRE and ASRM. Embryologist (Senior Clinical Embryologist certification, awarded by the ESHRE).

Adam Stencel MD
Specialist in obstetrics and gynecology. Certificate FMF

Doctor of Medicine – 2nd degree specialist in gynaecology and obstetrics. He has the FMF certificate of Competence. He is particularly interested in issues relating to gynaecology, treatment of couples infertility, prenatal diagnostics andultrasound imaging according to FMF standards.

Doctor is the member of the Polish Society of Reproductive Medicine (PSMR) and the Polish Gynaecological Society (PTG).

Piotr Głodek MD
Specialist in obstetrics and gynecology.

Second degree specialist in obstetrics and gynecology. Over 7 years of experience.

Andrzej Jeżak MD
Specialist in obstetrics and gynecology.
Michał Kunicki PhD, MD
Specialist in obstetrics and gynecology.
Doctor in Medical Sciences, 2nd degree specialist in gynaecology and obstetrics and the 2nd degree specialist in endocrinology. Physician with over 18 years of work experience in the treatment of couples infertility.

Doctor is the member of the European Society of Human Reproduction and Embryology (ESHRE), the Society of Gynaecological Endocrinology and the Androgen Excess & Polycystic Ovary Syndrome (AE-PCOS) Society. He is the author and co-author of scientific publications and conference reports.

Janusz Pałaszewski MD
Specialist in obstetrics and gynecology
Second degree specialist in obstetrics and gynecology.

Over 20 years of experience.

Mirosław Jakubów MD
Specialist in obstetrics and gynecology, specialist in endocrynology.

Second degree specialist in obstetrics and gynecology. Specialist in endocrynology. FMF certified.