reproductive medicine

Specialised tests for the female partner

These include imaging, genetic and immunology tests and advanced tests of the uterine lining – IMPO, immunology biopsy, microbiology biopsy. If a suspected condition cannot be diagnosed or treated conservatively, reproductive surgery modalities such as laparoscopy and hysteroscopy (including office hysteroscopy) come at hand. Which approach is best for your case is for your fertility consultant to decide, based on the specifics of your case.

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Imaging tests

Hysterosalpingography (HSG)

HSG is performed in the specialised X-Ray office on the hospital ground floor by a medical team consisting of a gynaecologist, a radiologist, and an anesthesiologist (if anaesthesia will be used). After patient preparation (vaginal disinfection) and placing a speculum, a contrast dye is introduced through the cervical channel using a metal catheter (thin tube). Contrast flows through the uterine cavity, enters the fallopian tubes, and if they are not blocked, it spills out into the abdominal cavity, where the body naturally absorbs it. If the tubes are blocked, the contrast matter cannot pass through them freely. After injecting the dye, a series of X-ray images are taken, documenting the fluid dynamics during its passage through the uterus and fallopian tubes.

Tubal patency is required for the natural meeting of the sperm and egg and for spontaneous conception to occur.

Blocked tubes hinder this process, and the desired pregnancy does not happen.

A hysterosalpingogram can inform us also about other conditions, like myomas, uterine polyps, adhesions, which could prevent embryo implantation or successful pregnancy.

HSG is done on the first clean (non-bleeding) days of the menstrual cycle before ovulation has occurred (up to about the tenth day of the cycle).

 

NB! Day one of your menstrual cycle is considered the first day of full flow bleeding.
Booking an appointment for an HSG can be done via the hospital

 call centre in the first days of your period. If you prefer to use anaesthesia for your HSG test, please make sure to tell our staff when booking.

Your fertility consultant will inform you about any tests and documents (informed consent form, pre-anaesthesia questionnaire, etc.) that you have to prepare in advance.

  • if you are pregnant;
  • if an active vaginal infection is present, or if you were diagnosed with pelvic inflammatory disease;
  • during menstrual bleeding;
  • if you are allergic to iodinated contrast media.

It is possible that you feel cramps similar to those in the first days of your period, but their intensity is strictly individual. In most cases, we recommend using pain relief medication, which your doctor will prescribe.

Depending on your pain threshold, the HSG test can be done under short intravenous anaesthesia. On the day your HSG is scheduled, you have to come to the hospital fasting, i.e., you should avoid all food and drink from the previous night.

The HCG test takes about 15 minutes to complete, and you will be required to stay in the office for about 10 minutes more (in case you had anaesthesia).

 

NB! Please keep in mind that your bladder should be empty before the HSG test.

Your fertility consultant will comment on the HSG results during a follow-up visit, for which you have to book an appointment. The commentary may be done on the same day as the test if you have booked an appointment in advance.

You can receive a digital copy of the HCG on a CD-ROM (an additional fee applies).

It is possible that after the test you have light spotting. If you feel pain though or bleeding intensifies, you should visit the Emergency office of Nadezhda hospital.

Reproductive surgery

01

Laparoscopy

Laparoscopy is an endoscopic surgical technique that uses a small cut in the abdominal wall through which a laparoscope is introduced inside the body. The laparoscope is a long thin tube (only a few millimetres in diameter) with a tiny camera at the end, used to visualise the abdominal cavity. This procedure allows the gynaecologist to diagnose and treat many diseases and conditions of the uterus, the ovaries, the fallopian tubes, the colon and the uppermost part of the cervix.

02

Hysteroscopy

Hysteroscopy is employed as a diagnostic method or a surgical treatment modality in some conditions. It is a detailed review of the uterine cavity utilising an optical telescope called a hysteroscope.

Д-р Георги Стаменов извъшва офис хистероскопия в болница "Надежда"

03

Office hysteroscopy

Office hysteroscopy is a minimally invasive procedure carried out in an outpatient setting without anaesthesia, which uses a mini-camera to inspect the female genital tract.

Д-р Георги Стаменов извъшва лазерна офис хистероскопия в болница "Надежда"

04

Laser office hysteroscopy

Nadezhda hospital also offers laser office hysteroscopy. This is a minimally invasive procedure, which uses a diode laser for the surgical removal of polyps and myomas. The procedure is performed in an office setting, without general anaesthesia.

Genetic tests

According to the current Bulgarian medical standard in Medical genetics, patients must sign an informed consent for every genetic test. We offer the following types of genetic tests:

Karyotyping is the gold standard when a genetic cause for infertility is suspected.

When is the test recommended:

In patients with fertility issues:

  • No pregnancy after trying to conceive for a year;
  • Unexplained infertility;
  • Birth of a child with a malformation syndrome;
  • Stillbirth;
  • Azoospermia, severe oligoasthenoteratozoospermia, amenorrhoea, early menopause;
  • Chromosomal aberrations detected by prenatal diagnosis;
  • Confirmed familial chromosomal rearrangements in family members.

In patients with developmental disorders:

  • Multiple hereditary abnormalities;
  • Clinical evidence for a chromosomal disease;
  • Disorders of growth, sex differentiation and development;
  • Intellectual deficit and behavioural abnormalities.

Carrier testing for fragile X syndrome is strongly recommended in women with oligomenorrhoea due to primary ovarian disfunction (incl. premature ovarian failure). Another indication is poor response to ovarian stimulation. If a premutation is confirmed, genetic counselling is recommended, as there is a risk for the birth of boys with intellectual impairment. In such cases,  preimplantation genetic testing can be recommended to rule out fragile-X syndrome.

The test is recommended for women who have a medical history of stroke, infarction, pulmonary thromboembolism, venous thrombosis, second-trimester miscarriage(s), stillbirth, or a first-degree family member (sibling or parent) who has such history or a confirmed clinically significant genetic thrombophilia.

Thrombophilias lead to an increased tendency for blood clotting. They can be caused by genetic and non-genetic factors (for example, immunological aberrations). About 40% of venous and arterial thrombosis cases are hereditary, yet, overall, thrombophilias are complex multi-factorial diseases and not the result of a single genetic abnormality.

The genetic variants most often screened in women with infertility are FV (Factor V Leiden mutation 1691G>A), FII (Factor II prothrombin – mutation G20210A), PAI-1 (Plasminogen activator inhibitor 1  – 5G/4G variant), MTHFR (Methylenetetrahydrofolate reductase – 677C>T and 1298A>C variants). Those variants are routinely screened in Nadezhda Hospital’s genetic lab.

The test is performed on venous blood samples, preferably drawn 30 to 60 minutes after eating. Results are available in one to two weeks.

Immunological tests

Immunological testing is assigned after a consultation with a clinical immunologist if you have problems conceiving, repeated pregnancy loss, or pregnancy complications.

In difficulties to conceive and patients with repeated pregnancy loss, the immunological analysis includes blood and endometrial testing. After pregnancy is achieved, monitoring of immunological parameters is done on peripheral blood samples.

Indices of cell immunity

Immunophenotyping of lymphocyte populations, Treg cells, determination of CD34 stem cells; functional cell tests – for cellular activity and proliferation.

 

Indices of humoral immunity

Serum immunoglobulins, complement fractions, autoantibodies.

Tissue compatibility parameters

Flow-cytometry cross-matching.

 

Endometrial markers of implantation

Flow cytometric immunophenotyping of endometrial cells from biopsy samples.

 

Serum angiogenic factors – PlGF, sFLT-1

Infertility is often due to problems causing embryo rejection even before the most sensitive tests could detect pregnancy. About 15-20% of all pregnancies end in spontaneous abortion, and the risk for this is elevated after each subsequent miscarriage.

Various autoimmune disorders can cause repeated pregnancy loss or recurrent implantation failure: antiphospholipid antibodies, antithyroid antibodies, antinuclear antibodies. Blood tests reveal an autoimmune problem in about 30% of women with the so-called ‘unexplained’ cases of repeated pregnancy loss. A woman can have one or several such disorders.

Two possible causes for alloimmune response can be responsible for a premature pregnancy loss – either the immune system fails to recognise the pregnancy, or the woman develops an abnormal immune response to the pregnancy.

Biopsies

1. IMPO

IMPO is an innovative diagnostic method developed in Nadezhda hospital that helps determine the implantation window. It is based on microscopical evaluation of tissue morphology and the presence of specific protein molecules.

The aim is to determine the best time for embryo transfer and if there is a risk of complications (implantation failure, miscarriage). If an elevated risk of complications is found, adequate treatment is administered before the embryo transfer procedure.

This is a specific period in the menstrual cycle, during which the uterus is most morphologically and physiologically prepared for embryo implantation. Usually, this period lasts between two and four days, and its occurrence and duration vary between women. In embryo transfer, it is essential that we take into account the individual characteristics of the implantation window for each woman. This guarantees a higher chance of a successful pregnancy.

The aim is to determine the best time for embryo transfer and if there is a risk of complications (implantation failure, miscarriage). If an elevated risk of complications is found, adequate treatment is administered before the embryo transfer procedure.

IMPO is indicated in repeated IVF failures and cases of menstrual cycle irregularities. In addition, this method can be applied with specific medical treatments that could lead to the displacement of the usual implantation window.

A biopsy sample of the uterine lining is taken on a specific day of the menstrual cycle, during the mid-luteal phase, when the implantation window is expected to occur normally. The endometrial biopsy is typically done five days after the start of progesterone administration in hormone-replacement cycles and seven days after the LH peak in natural cycles. After the samples are processed, immunohistochemical staining of tissue slices is performed, as well as microscopy, and the results report is prepared and sent to the fertility consultant in charge.

The standard time for reporting IMPO test results is two weeks after the biopsy. There is an option to request express processing and analysis, which will take only one week.

Based on the test results, the treating consultant can determine the best day for embryo transfer so that it falls within the implantation window of the patient and pregnancy chances are improved. In addition, the test is informative of whether an add-on treatment or modification of hormonal therapy is needed before embryo transfer.

Since its development and validation, this diagnostic method has been applied in more than 3000 patients.

The method is continuously reevaluated and updated, contributing to a significant increase of over 15% in success rates of embryo transfers after IMPO compared to the standard.

This implantation window assessment method was developed at Nadezhda hospital, and the form in which the results are reported was designed to meet the specifics of our approach. That is why specialists from other hospitals could misinterpret the information. Our partners from Sveti Ivan Rilski Medical Centre in Shoumen and Sveti Ivan Rilski Medical Centre in Tutrakan are an exception, as they have been thoroughly trained and instructed into the method.

2. Immunological biopsy

The immunological biopsy is an investigation of the uterine lining, which is done when deviations are suspected in the immune parameters of the endometrium that could be causing failed embryo implantation.

 

In preparation for the test, your fertility consultant will monitor the endometrium, and he will decide whether to do it during the natural cycle or with hormone-replacement therapy.

 

Your doctor will inform you about the date of your biopsy procedure and if any additional tests need to be done before it. 

The endometrial biopsy may feel like a more painful period, but it only lasts a few seconds, and therefore no pain medication is needed. In some cases, at the discretion of the fertility consultant, the biopsy can be performed under short intravenous anaesthesia.

 

NB! It is recommended that your bladder is full during the procedure.

After the biopsy, you may have spotting or light bleeding for a couple of days. If you feel stronger pain or bleeding intensifies, please visit the emergency office at hospital level -1 for an exam and consultation. 

Results from immunological biopsy typically come out in 3 to 4 days.

3. Biopsy for microbial culture

An endometrial biopsy for microbial culture is assigned when inflammation of the uterine lining is suspected. For example, if there are hysteroscopy findings suggestive of endometritis or abnormal results from IMPO and/or an immunological biopsy. In contrast to the other types of endometrial biopsy, a biopsy for microbiological culture can be done on any day of the menstrual cycle.

The endometrial biopsy may feel like a more painful period, but it only lasts a few seconds, and therefore no pain medication is needed.

After the biopsy, you may have spotting or light bleeding for a couple of days. If you feel stronger pain or bleeding intensifies, please visit the emergency office at hospital level -1 for an exam and consultation. 

Results from immunological biopsy typically come out in 3 to 4 days.

4. Biopsy for NAT-PCR testing

This endometrial biopsy obtains a sample for NAT-PCR testing to confirm the presence of various viruses, bacteria or intracellular parasites, which could cause inflammation of the uterine lining and prevent embryo implantation. These include ureaplasma, mycoplasma, chlamydia, trichomonas, gardnerella, and herpes.

Similar to the biopsy for microbial culture, the biopsy for NAT-PCR testing can be done on any day of the menstrual cycle.

The endometrial biopsy may feel like a more painful period, but it only lasts a few seconds, and therefore no pain medication is needed.

After the biopsy, you may have spotting or light bleeding for a couple of days. If you feel stronger pain or bleeding intensifies, please visit the emergency office at hospital level -1 for an exam and consultation.

Results from immunological biopsy typically come out in 3 to 4 days.

See also

Specialised tests for the male partner
Specialised procedures
Embryology lab
Andrology lab
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