ORIGYN – Tratamente infertilitate

Female Infertility

The human body is made of cells, and the DNA of each individual is concentrated in the cells’ nucleus. DNA is a map or a set of instructions which guide morphological development and complex, interdependent processes that enable the body to function normally.

PGT (preimplantation genetic testing) is usually recommended to couples in which one or both partners are known carriers of genetic mutations that may be transmitted to their offspring. This technique makes it possible to analyse one or more cells harvested from embryos produced by means of in vitro fertilisation. The objective is to identify, select, and transfer to the mother only embryos that do not feature the genetic anomaly for which the test was conducted.

PGT - the DNA analysis of the oocyte (polar body) or of the embryo (in cleavage or blastocyst stage) in order to identify the HLA type (human leukocyte antigens) or genetic anomalies. All preimplantation genetic testing techniques require a procedure of in vitro fertilisation.
All preimplantation genetic testing techniques require a procedure of in vitro fertilisation.

At Origyn Fertility Center, such techniques have been implemented successfully since 2014.

Tipuri de testare genetică preimplantațională:

Indications for PGT-A:

The age of the female partner > 35
Repeated failed implantations*
History of repeated abortions*
Male infertility with severely affected semen sample*

*It is recommended that the genetic karyotype of both partners be established.

Indications for PGT-M:

Prior pregnancy or child born with genetic diseases
Male partner with recessive autosomal disease
Female partner diagnosed with X-linked recessive disease
Male partner with autosomal dominant disease

Indications for PGT-SR:

Idiopathic infertility
High risk of miscarriage, especially during the first trimester
High risk for the foetus to be abnormal upon birth
Inherited chromosomal rearrangements - inversions, reciprocal translocations, Robertsonian translocations

Why PGT?

PGT eliminates the barriers related to the mother’s age, given the promising results in the case of women who are past the optimal age to bear children.
The success rate with regard to transferred embryos is superior.
Higher rates of genetically healthy babies.

How is an embryo genetically tested?

The procedure consists in the perforation of the area pellucida (the protective coating of the embryo) with the help of a laser beam. The embryologist extracts one or more cells from the embryo/embryos which are going to be analysed. The cells are harvested from the outer region called trophectoderm (the future placenta), without affecting the embryo’s inner cell mass. These will be tested in a state-of-the-art genetic laboratory.

Two or more cells are extracted from a single biopsied embryo, and the quantity of DNA is very small.

Stages:

The genetic material needs to be amplified.
Mutations in certain genes are identified using a modern technique of genetic sequencing called Next Generation Sequencing (NGS). This is a very accurate technique that can help identify single-nucleotide polymorphisms (SNPs).

The sampling of material for PGT does not affect the subsequent development of the embryos.

On day 5, the embryo is called a blastocyst and contains between 70 to 100 cells. At this stage, more cells may be harvested, thus increasing the reliability of the results. The disadvantage of the method is that, at this point, embryos are ready for implantation and so, until the results become available, they will need to be cryopreserved.

Only the genetically tested embryos which do not present any mutations or chromosomal aberrations will be transferred. The embryo transfer is done at a later date, in another cycle, and this decision is made jointly by the infertility specialist and the patients according to a well established protocol for getting the endometrium ready.

With the help of these techniques, the likelihood of obtaining a pregnancy after the IVF procedure is significantly increased. At the same time, the risk of spontaneous abortion is reduced. However, the approach does not guarantee that a pregnancy will be obtained, nor that a healthy baby will be born, as it does not cancel the need for prenatal tests in order to identify aneuploidy, such as the double test, non-invasive prenatal testing (NIPT), or the amniocentesis.

Male Infertility

Male fertility is affected in half of the couples struggling with infertility and, most often, this occurs without any worrrying symptoms of signs.

The semen analysis is an investigation which may provide useful information about male fertility and about what therapeutic approaches are suitable in each case. It should be carried out in Assisted Human Reproduction centres, according to the WHO 2010 criteria.

The possible causes of male infertility are investigated together with the urologist:

pre-testicular causes - the inadequate stimulation of the testicles by hormones produced in the brain
testicular causes - medical conditions affecting the testicles
post-testicular causes - obstructions, ejaculation and erectile dysfunctions

Risk factors associated with male infertility

Increased temperature in the area of the testicles: frequent sauna, constant heat exposure at the workplace
Exposure to radiations or toxic environments
Advanced age
Tobacco, alcohol or drug use
Sedentary lifestyle and obesity
Chronic conditions: diabetes mellitus, high blood pressure

The main medical conditions associated with male infertility:

Infections of the testicles, epididymis, prostate or seminal vesicles
Surgical interventions which affect the testicles or inguinal canal
Treatments for oncological conditions
Testicular tumours
The failure of the testicle to descend in the scrotum
Varicocele and other types of vascular conditions
Genital traumatisms
Testicle torsion
Genetic diseases or family history of genetic diseases
Infectious conditions - mumps

The semen analysis test
The semen analysis test is an essential investigation in the diagnosis of infertility, which is why any couple struggling to bear children should undertake it at an Assisted Human Reproduction centre, and then discuss the results with their attending physician.

Condiții și modalitate de recoltare:

Sexual abstinence is recommended for a minimum of 2 and a maximum of 5 days prior to the test. Your testicles produce a constant supply of spermatozoa, which are stored in the epididymis. This reservoir of spermatozoa takes approximately 2 to 3 days to fill, so, if the semen sample is collected within 2 days of sexual intercourse, the results will indicate a smaller number of spermatozoa. Also, the longer the spermatozoa spend in the epididymis, such as when more than 5 days pass since the last sexual intercourse, the more the results will show reduced motility and higher numbers of dead spermatozoa.
On presenting for the semen sample collection procedure, you must already have the test results for transmissible diseases: Hepatitis B and hepatitis C antibody tests (HBsAg, Hbc, HCV), the HIV test, syphilis serology (VDRL, RPR).
Wash your hands and genitalia with water and soap (the germs on your hands and skin may contaminate the semen sample and influence the interpretation of results)
(germenii de pe mâini și piele pot ajunge în sperma analizată și să afecteze interpretarea rezultatului)
Only use the special sterile recipient given to you at the clinic
Collect the entire semen sample produced after masturbation
Do not use lubricants
Close the recipient well
If you did not manage to collect the semen from the first ejaculation, inform the embryologist and schedule another semen analysis test in order to obtain relevant results.

The results of the semen analysis test. What semen properties are analysed?

The concentration. It indicates how many spermatozoa were found in a millilitre of ejaculated semen. The lower normal limit is of 15 million/ml. A result below this threshold is called oligospermia. The complete lack of spermatozoa is known as azoospermia, and an extremely low number is called cryptozoospermia.

The motility. Spermatozoa are categorised according to their ability to move. When fewer than 32% of spermatozoa are motile, the term used is asthenozoospermia.

The morphology. The shape and size of spermatozoa are analysed under the microscope, and at least 4% of the spermatozoa must appear normal for a morphology result within normal range. When this threshold is not reached, the condition is called teratozoospermia.

Leukocytospermia. The presence of leukocytes in the semen beyond 1 million/ml is abnormal and suggests an infection. The semen culture test will isolate the germ causing the infection and provide useful information for choosing the adequate antibiotic treatment.

The mixed antiglobulin reaction test (MAR) assesses the presence of antisperm antibodies.

These antibodies occur in cases of testicular trauma and surgical interventions to treat varicocele or inguinal hernia. They are clinically significant at levels higher than 50%. These antibodies cause the spermatozoa to agglutinate, preventing them from penetrating and progressing through the cervical mucus or from penetrating the oocyte.

Always discuss the results of the semen analysis test with the infertility specialist! Further investigations may be needed:

Urology / andrology consultation with a specialist in male infertility for the clinical examination of the genital organs and for a testicular ultrasound scan
A semen culture test, testing urethral secretions for Chlamydia, Mycoplasma
The semen DNA fragmentation test - Halosperm
A urine assessment - in retrograde ejaculation, after certain surgical interventions
Hormone blood tests: follicle-stimulating hormone (FSH), luteinising hormone (LH), inhibin B, prolactin
Genetic tests: karyotype, microdeletions of the Y chromosome, cystic fibrosis mutations (the CFTR test)
Epididymal puncture / Testicular biopsy

Intrauterine insemination (IUI)
In cases of idiopathic infertility (of unknown cause), or in case of minor problems with the semen analysis test, intrauterine insemination may be an option, but only if the female partner meets certain criteria as well - permeable fallopian tubes.

In vitro fertilisation (conventional IVF)
In cases for which IVF is recommended, conventional fertilisation may be carried out if the semen analysis test results are within normal range or show minor modifications.

The intracytoplasmic sperm injection (ICSI)
In case the result of the semen analysis test is especially poor, the ICSI technique is the most appropriate one. Using a microscope, the embryologist will select the best spermatozoa and will inject them in each oocyte extracted from the female partner via echo-guided ovarian drilling, thus optimising the outcomes.

The intracytoplasmic morphologically selected sperm injection (IMSI)
This technique is used when the semen analysis test results are extremely poor or if other fertilisation methods have already failed. The difference between ICSI and IMSI consists in the magnification power of the microscope used. With IMSI, even the smallest anomalies of spermatozoa can be detected, so only the spermatozoa with the best morphology can be selected for oocyte injection.

Testicular biopsy
In obstructive azoospermia, and sometimes even in cases of non-obstructive azoospermia, the testicular biopsy can be used to obtain viable spermatozoa for intracytoplasmic injection.

The therapeutic indication of ICSI/IMSI are:

Asthenozoospermia

Oligozoospermia

Teratozoospermia

Necrozoospermia

Over 50% antisperm antibodies

More than 4 years of infertility of unknown cause

Over 15% spermatozoon DNA fragmentation

History of failed IVF fertilisation attempts

How can you prevent fertility problems?

Give up unhealthy habits such as smoking, taking steroids and anabolic supplements, or doing drugs
Protect yourself efficiently from contracting sexually transmitted disease during sexual intercourse and get screened regularly
Optimise your body weight if your Body Mass Index (BMI) is above normal
Maintain optimal sexual and reproductive function by sport and healthy eating
Seek specialist medical assistance promptly for any genital problem
Consider having your semen preserved by freezing in case you will undergo surgery, chemotherapy, radiotherapy, or if you have a family history of genetic diseases or fertility problems.

Treatments

During a menstrual cycle, several follicles begin to develop under the influence of the follicle stimulating hormone (FSH). Their number depends on the woman’s ovarian reserve, which may be assessed by measuring the AMH level (the anti-Mullerian hormone) and by doing an endovaginal ultrasound in the menstrual phase. The female body is programmed to select only one follicle to grow larger than the others, reach maturity, and ovulate on the day the luteinising hormone (LH) is discharged. This is how ovulation occurs naturally.

Ovarian stimulation aims to boost the development of follicles at the start of the cycle, uniformly, as well as to block their ovulation so that they may be drilled for the extraction of the oocytes inside. The female patient with self-administer ovarian stimulation treatment daily. This consists of two distinct oral or injected medications, one which contains FSH (the follicle stimulation hormone), and one which blocks ovulation depending on the protocol (long or short).

Throughout the stimulation period, several ultrasound scans and hormonal assessments will be performed. When the follicles are of optimal size (at least 3 are bigger than 17 mm), the ovulation will be triggered and, 36-38 hours from this final outcome, the oocytes will be harvested by means of echo-guided ovarian drilling.

Ovarian stimulation may be used as such to treat ovulation disorders or to increase the success chances of assisted reproduction (mild ovarian stimulation for intrauterine insemination, or ovarian stimulation as part of an in vitro fertilisation protocol).

When is ovarian stimulation recommended?

Hormonal dysfunctions
Menstruation and ovulation disorders
In assisted reproduction - intrauterine insemination or in vitro fertilisation (IVF)

How is it administered?

The doses and protocol are decided by the specialist and tailored to each patient.
Orally or by injection, at home.
For a period of 5-10 days, depending on the patient’s response to the treatment.
With monitoring by means of ultrasound and hormone level tests

What are the risks?

Multiple pregnancy, especially in the case of mild stimulation followed by guided sexual intercourse or intrauterine insemination
Adverse effects to the medication: Abdominal discomfort, bloating, discomfort or small hematoma at the injection site, allergic reactions, and, rarely, ovarian hyperstimulation syndrome (OHSS)

Most injections are done subcutaneously, with fine needles, and the patients can do them themselves painlessly and with minimal discomfort.

Notify the doctor and the clinic in case of any unwanted reaction during treatment.

At Origyn, we understand that each infertile couple is unique. We tailor protocols to address the individual needs of the patients in order to optimise the therapeutic response and to increase the rate of success.

The choice of stimulation protocol and dosage depends on several factors:

The level of AMH - the anti-Mullerian hormone provides useful understanding of the woman’s ovarian reserve, as it tends to decrease by approx. 0.1-0.2 ng/ml/year
The AFC - the antral follicular count indicates the number of antral follicles that can be identified by means of ultrasound at the beginning of the menstrual cycle
Age
Weight and the Body Mass Index (BMI)
Associated pathologies - endometriosis, male pathologies

Sometimes, ovaries may not respond to the stimulation treatment, in which case it is recommended to cancel and reschedule the procedure for another cycle. A treatment cycle may be cancelled when:

The ovary does not respond adequately to stimulation
The ovary responds excessively, which may lead to ovarian hyperstimulation syndrome (OHSS)
If there is a risk of hyperstimulation or for any other reason (e.g., the patient develops an endometrial polyp during stimulation), the doctor may recommend a “freeze all” procedure; this consists of collecting and fertilising the oocytes, then cryopreserving the resulting embryos so that they may be transferred into the uterus in a subsequent cycle.
Because a pregnancy increases the risk of ovarian hyperstimulation syndrome (OHSS), vitrifying all embryos is the preferred solution for patients already at risk. In this way, the ovaries return to their initial dimensions before the embryo transfer is performed. Another ovarian stimulation treatment is no longer necessary for embryo transfer; preparing the endometrium for transfer is sufficient.

Techniques

Intrauterine insemination

Intrauterine insemination (IUI) is a technique of assisted human reproduction (AHR) which helps couples with ovulation dysfunction, cervical pathology, vaginismus and other sexual disorders, mild endometriosis (stage I-II), or minor modifications of the semen analysis test results.

When the monitored female patient ovulates, spontaneously or as a result of mild ovarian stimulation, a semen sample from the male partner is introduced into the uterus with the help of a catheter and ultrasound guidance. In this way, the spermatozoa need to travel a shorter distance, with greater chances that the gametes meet and fertilise. The success rate for IUI varies from one couple to another depending on the cause of infertility, the age of the female patient, and the number of infertile years. The cumulative success rate for 3 procedures can reach approximately 15-25%.

Assessing the permeability of the fallopian tubes - The HyCoSy investigation

Before an intrauterine insemination, the fallopian tubes must be assessed!

The best outpatient method for investigating the status of the fallopian tubes is the hysterosalpingo contrast sonography (HyCoSy). Some of its advantages are:

It is easy to perform, and the procedure only takes approximately 15 minutes
It avoids the disadvantages of the hysterosalpingography (HSG): intense pain, risk of infection, exposure to radiation, exposure of the endosalpingeal tissue to iodine.
It allows for “real-time” assessment of the tubes’ condition
It permits the simultaneous assessment of the uterus (revealing the presence or absence of synechiae, septa, polyps, fibromas, or uterine malformations) and of the ovaries (for the antral follicular count or the identification of a variety of cysts - serous, haemorrhagic, endometrial, teratomas).

At Origyn Fertility Center, the hysterosalpingo contrast sonography (HyCoSy) is performed using the Sono-Vue contrast substance and software for 3D and HD live viewing. The procedure is part of our Initial Infertility Assessment protocol.

The procedure is done in the first part of the menstrual cycle and preparing for it is relatively simple. First, the doctor explains the procedure to the patient in order to prevent fear and psychological stress.
About 15-30 minutes before the procedure, an antispasmodic is injected intramuscularly. Also, the patient must have a Papanicolau test done and present with negative cervical smear results no older than a year prior to the HyCoSy procedure.

In vitro fertilisation

In vitro fertilisation refers to the fertilisation of sexual cells (oocytes and spermatozoa) outside of the human body, in vitro, in carefully controlled conditions which imitate the uterine environment and allow the feeding and the division of embryos up to the 5th culture day, when they can be transferred into the uterus or vitrified for transfer in a subsequent cycle.

When is in vitro fertilisation recommended?

Impermeable or absent fallopian tubes
Advanced endometriosis (stage III-IV)
Ovarian insufficiency or poor ovarian reserve (low AMH level)
Failure after 3 intrauterine inseminations (IUI)
Severely altered semen analysis test results: Teratozoospermia, severe oligozoospermia, severe asthenozoospermia, positive MAR test results
In vitro fertilisation with donated oocytes
Couples with genetic pathology which requires preimplantation genetic testing (PGT)

In vitro fertilisation with donated oocytes

When are a woman’s own oocytes no longer viable and an IVF procedure with donated oocytes is recommended instead?

Advanced maternal age or patient already menopausal
Failed repeated IVF procedures using own oocytes
Precocious ovarian insufficiency - very low AMH level
Maternal genetic diseases

What does the procedure of importing oocytes consist of? How do we choose the donor?

At the clinic, patients discuss the appropriateness of the procedure with their infertility specialist, and then fill out an application for the National Transplant Agency to authorise the import of oocytes. The oocytes are imported from an accredited cell bank, and the anonymous oocyte donors are rigorously screened for genetic and infectious viral diseases. Each couple chooses oocytes from a donor whose phenotype is similar to that of the female partner (colour of the skin and eyes, height, weight, blood type and Rh). In this way, the future child will share certain features with the mother. Once the import order is issued, the oocytes arrive at our clinic and are safely stored until use.

How do we prepare for the IVF procedure with donated oocytes?

Patients must first undergo a standard set of tests (viral screening, blood type and Rh tests, semen analysis test), and then the female patient will follow a protocol to prepare her endometrium for embryo transfer. When the oocytes are thawed in the laboratory, the male partner will give a semen sample at the clinic and his spermatozoa will be injected in the woman’s oocytes (ICSI); then, when all the criteria are met, generally 5 days later, the embryo transfer can take place.
The success rate in such cases is quite high (50-70%) because the oocytes are collected from young donors. However, the outcomes also depend on the age and comorbidities of the recipient.

Cryopreservation

Cryopreservation is a method of storing gametes and supernumerary embryos so that they may be used in a subsequent cycle. The cryopreservation of gametes can be a way to preserve the fertility of patients at risk of diminishing fertility or of infertility, such as cancer patients and patients with a high risk of losing ovarian function. The cryopreservation of supernumerary embryos obtained during a stimulation cycle increases the chances of an infertile couple to bear children later on.

Vitrification - the newest and most commonly used freezing method.
The cryopreservation of embryos, spermatozoa, and oocytes may be achieved either by slow freezing or by vitrification.
At the Origyn Fertility Center, we only employ vitrification (since 2014), and our embryologists are very experienced in the freezing/thawing of vitrified embryos and gametes. Vitrification is the newest method of cryopreservation, and it entails the use of a highly concentrated cryoprotective agent when performing the ultrafast freezing of cells in order to avoid the risk of ice crystals forming and destroying the cells, such as may happen during slow freezing. According to research comparing the two techniques, vitrification is substantially better than slow freezing.

Embryo transfer

The embryo transfer is the final stage in an assisted human reproduction procedure; it consists in the transfer of one or more embryos into the uterus, either as a so-called fresh transfer (of embryos from the same cycle for which the patient underwent stimulation treatment), or as a frozen embryo transfer (after thawing an embryo from a previous cycle and preparing the uterus), all according to a protocol intended to maximize the implantation success rate. It has been scientifically proven that the embryo transfer technique plays an important role in the outcomes of assisted human reproduction cycles, apart from the quality of the embryos and the woman’s endometrial receptivity.

The embryo transfer is the stage that brings the work of the entire medical team to fruition, and it must be conducted with utmost care and appreciation of its importance.
Although it is not a painful procedure, it does require anaesthesia. With the female patient lying in gynaecological position, an assistant will use a vaginal speculum and wash the vagina with saline solution and sterile pads. Also, an assistant will hold the transabdominal ultrasound probe in the required position for viewing the uterus. With the help of a very fine and soft catheter inserted through the cervix, the doctor will place the embryo in the uterus and the procedure will be visible on the screen of the ultrasound machine; the patient, too, may watch the entire process. We recommend that patients follow the guidance of our clinical staff and to drink a large quantity of liquids before the procedure in order to facilitate the embryo transfer.

Diagnosis

The decision to see a specialist in assisted human reproduction is the most important step in addressing infertility.

Infertility concerns both partners in a couple, so it is very important for both to attend the initial consultation in order to conduct a thorough anamnesis (interview) and compile a detailed medical file with personal information which will guide the diagnosis and treatment process.

We recommend that you bring all the relevant medical documents when presenting, especially the results of laboratory tests and/or past surgical interventions, which are necessary in order to attain an accurate understanding of your situation.

At Origyn, our approach is tailored to each infertility case. We promote open communication with our patients, and we encourage you to bring up all your questions and concerns as early as the initial consultation. Together with our specialists, the optimal treatment strategy will be decided in order to achieve the desired outcome - a pregnancy.

Once the results of the recommended preliminary tests are available, a follow up consultation is scheduled for the interpretation of results and selection of appropriate procedure depending on the causes of the infertility and the particular characteristics of each couple.
The infertility investigations may be done in a single day, an approach that Origyn Fertility Center introduced in 2015. The diagrams below illustrate the workflow of the single-day diagnostic process and the paraclinical investigations that we recommend to our patients.

Genetic testing

PGD (preimplantation genetic testing) is usually recommended to couples in which one or both partners are known carriers of genetic mutations that may be transmitted to their offspring. This technique makes it possible to analyse one or more cells harvested from embryos obtained by means of in vitro fertilisation, so that only the embryo/embryos which do not feature the genetic anomaly for which the test was conducted get transferred to the mother-to-be.

When is preimplantation genetic diagnosis recommended?

One or both parents are carriers of hereditary genetic diseases.
One of both parents feature an altered karyotype (according to chromosomal testing) due to the presence of a chromosomal anomaly such as chromosomal translocations or inversions.
Repeated failed IVF or ICSI attempts
Repeated embryo implantation failure (RIF)
Recurrent miscarriage
Advanced maternal age (especially after the age of 38-40)
History of foetal aneuploidy (abnormal number of chromosomes in a cell) in previous pregnancies
Certain cases of male sterility, such as when the semen sample is collected straight from the epididymis or testicle.

Preimplantation genetic screening (PGS) is a technique used in the field of assisted human reproduction and which includes the analysis of the 23 pairs of chromosomes normally present in a cell. PGS does not seek to detect a particular genetic disease, but to assess the number of chromosomes in a cell and, thus, help identify a range of anomalies.

When is preimplantation genetic screening recommended?
Advanced maternal age
Couples with repeated failed IVF
Couples with a history of recurrent miscarriage
Couples with repeated aneuploid pregnancies
Male partner suffering from severe infertility
At Origyn Fertility Center, such techniques have been implemented successfully since 2014.

Surgical Infertility Treatment

Infertility is a couple’s inability to obtain a pregnancy within a year of unprotected sexual activity. The decision to see a specialist in assisted human reproduction is the most important step in addressing infertility.

At present, surgical infertility treatment consists in minimally invasive procedures which aim to preserve and restore normal anatomy, as well as enable the patient to recover quickly and easily, with minimal complications. When choosing the type of surgery, keeping the ovarian reserve unaltered is of utmost importance.

At Origyn, our clinicians are highly specialised in hysteroscopy, resectoscopy, laparoscopy, and interventions on the cervix, following participation in numerous training courses and practical internships both in Romania and abroad.

Hysteroscopy

What is hysteroscopy?
Hysteroscopy is a method of inserting a hysteroscope through the vagina into the uterus and using its optical system to investigate the uterus in order to diagnose and treat various medical conditions.

Types of hysteroscopy

diagnostic hysteroscopy - it entails the inspection of the uterus and assessment of any visible pathology
operative hysteroscopy - it is a minimally invasive procedure involving the use of a surgical sheath, scissors, and forceps.

Indications of hysteroscopy

Presence of an endometrial polyp
Presence of a synechia in the uterus / Asherman’s syndrome
Presence of a uterine septum or malformation anomaly which may be surveyed using 3D ultrasound reconstruction techniques - unicornuate uterus, bicornuate uterus, didelphic uterus
Suspected chronic endometritis
Presence of endometrial hypertrophy
Examination of the uterus prior to embryo transfer
Examination of the uterus after a miscarriage/curettage
Diagnosis of an isthmocele - a post caesarean section defect
Diagnosis and treatment of cystic adenomyosis

The absolute contraindications of hysteroscopy

Untreated vaginal infections
Papanicolau smear test results not available/abnormal

Is anaesthesia necessary?
Hysteroscopy is not a painful procedure, and the discomfort is less than the usual menstrual cramps.
Anaesthesia is required in certain situations:

In case of an operative hysteroscopy procedure which is expected to take longer and stimulate more intense painful responses
If the patient has a low pain threshold or is feeling anxious about the procedure

Scheduling a hysteroscopy
The procedure must be scheduled on the first day of menstruation for a convenient time in the interval between the end of menstrual bleeding and day 11-12 of the menstrual cycle.

Investigations required prior to a hysteroscopy

Routine tests: Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).

Important instructions to follow on the day of the hysteroscopy

The bladder must be emptied for the hysteroscopy procedure.
In case of anaesthesia, the patient should not eat or drink on the day of the intervention.

Diagnostic hysteroscopy
The patient will lie in gynaecological position, just like for a routine consultation.
A sterile perineal drape is used to isolate the site and the vulvovaginal and exocervical areas are cleansed with betadine.
The hysteroscope is inserted through the vagina and then the cervical canal until it reaches the uterus.
During the hysteroscopy, the uterine cavity is measured and the appearance, vascularization and mucosal folds of the endometrium are assessed.

The hysteroscopy ends with endometrial scratching - using the hysteroscope to make small “scratches” on the endometrium.

Operative hysteroscopy
The steps of an operative hysteroscopy are the same as for a diagnostic hysteroscopy.
The operative hysteroscopy helps address medical conditions which require surgical sectioning/biopsy, such as endometrial polyps, uterine septa, endometrial hypertrophy etc.
The biopsy samples taken from endometrial polyps or hypertrophied mucosal folds are send of anatomopathological analysis.

Interesting facts
Chronic endometritis, which is the chronic inflammation of the endometrium, does not manifest any clinical symptoms but it creates a hostile environment inside the uterus for embryo implantation and pregnancy.
The endometrial scratching improves the chances of obtaining a pregnancy in the 3-6 months following the procedure.

Laparoscopy

What is laparoscopy?
Laparoscopy is a method of exploring the peritoneal cavity by inserting trocars through subumbilical incisions (left and right iliac fossae and suprapubic) in order to diagnose and treat a range of medical conditions, including gynaecologic.

Types of laparoscopies

Diagnostic laparoscopy - the inspection of the female reproductive system (the uterus, fallopian tubes, and ovaries) and it can be used to assess tubal permeability, diagnose endometriosis or the Fitz-Hugh-Curtis syndrome (an inflammatory disease caused by Chlamydia infection)
Operative laparoscopy - invasive procedures on the female reproductive system with the help of specialised laparoscopic tools such as atraumatic and traumatic graspers, scissors, bipolar and monopolar clams, special sutures.
Adhesiolysis - the detachment of inflammatory or postprocedural adhesions in order to restore normal pelvic anatomy
Unilateral or bilateral salpingectomy - the surgical removal of a fallopian tube affected by hydro/haemato/pyosalpinx
The excision of ovarian cysts and cyst lining
Myomectomy - the surgical removal of uterine myomas (muscle tumours)
Hysterectomy - the surgical removal of the uterus (with/without the ovaries)
The evacuation of an ectopic pregnancy
Establishing the stage of endometriosis
Assessing the functionality of the fallopian tubes - the dye test
Investigating the malformations of the female reproductive system

The indications of diagnostic laparoscopy

Untreated vaginal infections
Papanicolau smear test results not available/abnormal
Pregnancy developing normally inside de uterus
Medical contraindications - cardiovascular and pulmonary diseases which do not allow safe general anaesthesia
Obesity (BMI > 30)
Scarred abdomen - history of substantial abdominopelvic surgical interventions

Is anaesthesia necessary?
Yes, it is! Laparoscopy requires general anaesthesia with orotracheal intubation.
This is why, prior to the intervention, the patient must present for a cardiology consultation and receive medical approval for general anaesthesia.

How long does a laparoscopic procedure take?
The diagnostic laparoscopy takes approximately 30 minutes, while operative laparoscopy can require up to several hours depending on the complexity of the pathology which it is intended to treat.

Scheduling a laparoscopy
The procedure must be scheduled on the first day of menstruation for a convenient time in the interval between the end of menstrual bleeding and day 11-12 of the menstrual cycle.

Investigations required prior to a laparoscopy

Routine tests Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).
Cardiology consultation
Electrocardiography
Posteroanterior thoracic X-ray

Important instructions to follow on the day of the laparoscopy

Laparoscopy requires digestive preparation the day before. This consists in administering laxatives to empty the bowels and facilitate the surgeons’ access in the pelvic area.
Also, a urinary catheter is inserted before the laparoscopy itself can begin.
The patient is required not eat or drink on the day of the intervention.

The laparoscopy procedure
The patient will lie in gynaecological position, just like for a routine consultation.
General anaesthesia is carried out by means of orotracheal intubation.
When hysteroscopy is also recommended, both interventions can be performed on the same occasion and under the same general anaesthesia.
During laparoscopy, the female reproductive organs and the anatomical structures of the peritoneal cavity are examined.
If any adhesions are found, the surgeons will remove them (adhesiolysis) before moving on to assess the permeability of the fallopian tubes and resolve the specific pathology for which the intervention was scheduled.
Samples of excised material is sent to the laboratory for anatomopathological examination.
Bipolar clamps are used to check haemostasis.
The peritoneal cavity is cleansed.
The trocars are removed with video guidance, the intraabdominal gas is removed (exsufflated), and the surgical incision is sutured.

How long do I need to stay in hospital?
After a laparoscopic procedure, be it diagnostic or interventional, overnight hospitalisation is needed for the postoperative monitoring of physiological parameters, the clinical recovery, the resumption of bowel activity, assisted mobilisation, and the wearing off of anaesthesia medication effects.
On the second day, the postoperative wounds are cleaned and redressed.
Post-procedural treatment and recommendations
Depending on the intraoperative findings, the specialist will establish the appropriate treatment plan.
The patient is not advised to drive upon being discharged.
After the procedure, there needs to be a gradual return to regular eating habits. Until bowel function resumes, the patient is allowed to eat vegetable soup, cream soup, low-fat yoghurt, low-fat cheese, digestive crackers, soft-boiled eggs. Grilled chicken and vegetable soup can be added once bowel activity is restored, and then the patient can continue to eat normally.

The patient can tend to the surgical wounds at home, cleaning and redressing them every 2 days, and then present for the removal of the sutures 7 days after the procedure.
The patient needs to rest and abstain from sexual intercourse according to the recommendations of the attending physician.
The anatomopathological results take about 7-14 days.

Interesting facts
The permeability of the fallopian tubes can be performed with 100% accuracy and specificity by means of diagnostic laparoscopy and the tubal permeability test called the dye test because it uses methylene blue.

The cone biopsy

The cone biopsy is both a biopsy and a therapeutic procedure by which a wire loop connected to a source of monopolar electrical current is used to cut out cervical tissue previously diagnosed as dysplastic after a Papanicolau smear test and colposcopy.
The indications of a cone biopsy

Cervical dysplasia diagnosed with a Papanicolau smear test

Is anaesthesia necessary?
Yes, it is! The cone biopsy procedure entails the surgical excision of the part of the cervix previously found to be affected by dysplasia. The intervention can take up to 30 minutes and it requires the patient to remain in a relaxed, painless state.
Scheduling a cone biopsy
The appointment must be made on the first day of menstruation. The period of menstrual bleeding is avoided.

Investigations required prior to a cone biopsy

Routine tests: Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).
HPV typology test
Colposcopy

Important instructions to follow on the day of the cone biopsy

The bladder must be emptied for the procedure.
Because the procedure is done under general anaesthesia, the patient should not eat or drink on the day of the intervention.

The cone biopsy procedure
The patient will lie in gynaecological position, just like for a routine consultation.
A sterile perineal drape is used to isolate the site and the vulvovaginal and exocervical areas are cleansed with an antiseptic.
Lugol solution is used to mark the lesions that will be excised with a special electrical wire loop under colposcopy supervision. Bleeding is controlled by means of diathermic coagulation.
The tissue sample is sent to the laboratory for anatomopathological analysis. The anterior and posterior lips of the cervix are referenced on the sample.

Post-procedural treatment and recommendations
Depending on the intraoperative findings, the specialist will establish the appropriate treatment plan as well as the need for another, follow up procedure for the surgical treatment of the identified pathology.
Sexual intercourse, vaginal treatments, and bathing in a tub are not allowed for a period of 2-3 months after the cone biopsy.
The follow up clinical assessment and other investigations such as the Papanicolau smear test, viral HPV typology, and colposcopy are carried out according to the recommendations of the attending physician.
The anatomopathological results take about 7-14 days.

Interesting facts
For pregnant patients with a history of cone biopsy interventions, vaginal pessary is recommended in order to support the cervix and prevent abortion or preterm delivery.

The resectoscopy

What is a resectoscopy?
Similar to a hysteroscopy, the resectoscopy is a minimally invasive transvaginal procedure used in the surgical treatment of certain uterine pathologies with the help of an instrument called resectoscope.

How does a resectoscope differ from a hysteroscope?
The resectoscope uses bipolar electrical current to cut through tissue in order to excise diseased structures and, at the same time, control bleeding.
It is equipped with an aspiration tube which also facilitates better viewing of the uterine cavity during the intervention.

Types of resectoscopy

Depending on the diameter of the resectoscope, the resectoscopy may or may not require the dilation of the cervical canal. The resectoscope used at the Origyn Fertility Center allows access into the uterine cavity without prior dilation of the cervical canal.
Depending on the type of wire loop
The needle electrode - for cutting out a uterine septum/synechia.
The wire loop - for cutting polyps/intracavitary fibroids/hypertrophied endometrial sections into slices to be evacuated afterwards.

The indications of resectoscopy

Presence of an endometrial polyp
The presence of a synechia in the uterus / Asherman’s syndrome
The presence of a uterine septum or malformation anomaly which may be surveyed using 3D ultrasound reconstruction techniques - unicornuate uterus, bicornuate uterus, didelphic uterus
Presence of endometrial hypertrophy

The contraindications of resectoscopy:

Untreated vaginal infections
Papanicolau smear test results not available/abnormal

Is anaesthesia necessary?
Yes, it is!

Although the dilation of the cervical canal is not necessary, the resectoscope is larger in diameter than the hysteroscope (5 mm compared to 2.9 mm), which makes the insertion of the resectoscope through the cervical canal problematic without anaesthesia.
Because resectoscopy is an interventional procedure, it takes longer to complete.
The use of bipolar electrical current also justifies the need for general anaesthesia.

Scheduling a resectoscopy
The appointment must be made on the first day of menstruation. The procedure must be scheduled on the first day of menstruation for a convenient time in the interval between the end of menstrual bleeding and day 11-12 of the menstrual cycle.

Investigations required prior to a resectoscopy

Routine tests: Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).

Important instructions to follow on the day of the resectoscopy

The bladder must be emptied for the hysteroscopy procedure.
Because the procedure is done under general anaesthesia, the patient should not eat or drink on the day of the intervention.

The resectoscopy procedure
The patient lies down in gynaecological position, just like for a routine consultation.
A sterile perineal drape is used to isolate the site and the vulvovaginal and exocervical areas are cleansed with betadine.
The resectoscopy may be preceded by a diagnostic hysteroscopy if the clinician considers it necessary.
The resectoscope is inserted through the vagina and then the cervical canal until it reaches the uterus.
The goal of resectoscopy can be to excise endometrial polyps, intracavity fibroids, hypertrophied sections of the endometrium (sending samples to the laboratory for anatomopathological analysis), or to restore the normal anatomy of the uterine cavity by cutting out a uterine septum or intracavitary adhesions (synechiae).

Interesting facts
Resectoscopy provides a surgical solution to intracavitary fibroids of up to 40 mm in diameter without the need for conventional open surgery or laparoscopy.
The surgical treatment of a uterine septum is necessary in order to prevent impaired foetal development, abortions late into the pregnancy or preterm delivery.

The ultrasound-guided ovarian drilling

What is the ultrasound-guided ovarian drilling?
The ultrasound-guided ovarian drilling is a procedure by which the ovaries are punctured in order to aspirate the follicular fluid and, with it, the ovarian follicles; it is typically done transvaginally or, more rarely, transabdominally, and it requires general anaesthesia.

Types of ovarian drilling

Ovarian drilling during a natural menstrual cycle, when the patient’s own hormonal reserves can produce 1 or 2 follicles without prior administration of ovarian stimulation medication
Ovarian drilling after controlled ovarian stimulation for 9-11 days according to a simulation protocol established by the specialist. The procedure leads to the extraction of 3 or more oocytes to be used for in vitro fertilisation depending on the specific details of the case.

The indications of ovarian drilling

In vitro fertilisation
Oocyte preservation when removing endometriotic cysts via a puncture procedure and scheduling in vitro fertilisation for the next menstrual cycle

Is anaesthesia necessary?
Yes, it is! Anaesthesia is necessary to keep the patient relaxed and prevent sudden movements (e.g., due to pain) during the procedure, which can take up to 30 minutes and which requires precision for the puncture of ovarian follicles via transvaginal access. Also, it is important to prevent intraoperative accidents such as damaging adjacent structures, blood vessels, or intestines.
In exceptional cases and on natural menstrual cycles only, it is possible to avoid anaesthesia if both the patient and clinician consent.
Scheduling an ultrasound-guided ovarian drilling
The ultrasound-guided ovarian drilling procedure for the purpose of in vitro fertilisation is done 36-38 hours after the ovulation trigger is administered.

Investigations required prior to ovarian drilling:

Routine tests: Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).

Important instructions to follow on the day of the ovarian drilling

The bladder must be emptied for the procedure.
Because the procedure is done under general anaesthesia, the patient should not eat or drink on the day of the intervention.

The ultrasound-guided ovarian drilling procedure
The patient will lie in gynaecological position, just like for a routine consultation.
The patient lies down in gynaecological position, just like for a routine consultation.
The ovaries are found using an endovaginal ultrasound probe and then the ovarian follicles are punctured with the help of an ultrasound-guided system which aspirates the follicular fluid.
The embryologist analyses the follicular fluid under a microscope inside a special hood that keeps the samples at human body temperature.
After all the follicles are aspirated and the ultrasound scan confirms haemostasis, the vaginal area is cleansed.

Post-procedural treatment and recommendations
The optimal treatment plan for embryo transfer or embryo/follicle freezing will be decided depending on the patient’s hormonal levels, the number of her follicles, the preimplantation diagnosis or the need for additional investigations and interventions.
Prophylactic antibiotic treatment is necessary both during and after the procedure.
The patient is advised to avoid physical exertion and sexual intercourse, sudden movements, bathing in a tub, and bowel movement problems.

Interesting facts
The maximum number of oocytes that can be extracted by means of ultrasound-guided ovarian drilling is equal to the number of ovarian follicles. Because not all the follicles always contain oocytes, the procedure may result in fewer extracted oocytes than the number of follicles.
Also, because oocytes mature at different rates, some immature oocytes may be extracted during the ovarian drilling, and these will not be useful for fertilisation procedures.

The testicular puncture

What is a testicular puncture?
The testicular puncture is a procedure by which an incision is made into the scrotum and testicle to collect small samples of testicular tissue which the embryologist can analyse under the microscope in order to extract spermatozoa; the intervention requires general or spinal anaesthesia.

The indications of testicular puncture

In vitro fertilisation by means of ICSI and IMSI techniques in the case of patients diagnosed with obstructive azoospermia.

Is anaesthesia necessary?
Yes, it is! Either general or spinal anaesthesia is necessary, depending on the recommendation of the anaesthesiologist, because this is an invasive procedure that entails the surgical puncture of the testicle, the cutting out of tissue samples, and anatomical suturing.

Scheduling a testicular puncture
The testicular puncture is scheduled after the partner’s ovarian drilling, and both are done on the same day. As soon as the mature oocytes are collected, the testicular puncture is carried out in order to select viable spermatozoa for immediate injection in the partner’s oocytes.

Investigations required prior to a testicular puncture::

Routine tests: Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).

Important instructions to follow on the day of the testicular puncture

The bladder must be emptied for the procedure.

The testicular puncture procedure
The patient lies down in dorsal decubitus position.
A sterile perineal drape is used to isolate the site and the genital organs are cleansed with betadine.
An incision is done into the scrotum and the layers protecting the testicle, and then small samples of testicular tissue are cut out. The incised structures are anatomically sutured once haemostatic control is achieved.
The embryologist analyses the testicular samples under a microscope inside a special hood that keeps the samples at human body temperature.
In case no spermatozoa are found in the first incised testicle, the second one is punctured according to the same procedure.

Post-procedural treatment and recommendations
Prophylactic antibiotic treatment is necessary both during and after the procedure.
After the intervention, it is necessary for the patient to rest, to abstain from sexual activity, to maintain strict hygiene and to present for the removal of the sutures according to the recommendations of the urologist.

Interesting facts
Before a testicular puncture, it is recommended to first obtain semen samples from a donor in case no viable spermatozoa are found during the procedure. This allows embryos to still be obtained and later on transferred.
In case the couple do not wish to use semen from a donor, the oocytes extracted during the ovarian drilling are frozen.

Intrauterine insemination

What is an intrauterine insemination?
The intrauterine insemination (IUI) is the insertion into the uterus of a semen sample from the partner or a donor after the sample has been adequately prepared in the laboratory using a centrifuge technique. The procedure is done 36-40 hours from the onset of the ovulation process.

The indications of intrauterine insemination

Couple diagnosed with infertility
Normal semen sample - normozoospermia
Female partner with permeable fallopian tubes

The absolute contraindications of intrauterine insemination

Female partner with impermeable fallopian tubes
Abnormal semen sample - teratozoospermia
Papanicolau smear test results not available/abnormal

The relative contraindications of intrauterine insemination

ENDOMETRIOSIS
Low ovarian reserve
The teratozoospermia index TZI > 1.5

Intrauterine insemination may be carried out using:

The patient’s own hormone reserves - normal menstrual cycle
Letrozole - an aromatase inhibitor
Small doses of FSH products

The stages of insemination
Day 1 of the menstrual cycle - the patient notifies the clinic about the onset of her menstruation
Day 2 of the menstrual cycle - the patient has an endovaginal ultrasound scan and her hormone levels are assessed
Based on the characteristics of each couple, the specialist establishes the optimal treatment plan.
Day 6-8-10 - the ultrasound scan and hormonal assessment are repeated
When the size of the dominant follicle exceeds 17 mm, ovulation is triggered with the help of human chorionic gonadotropin (hCG).
The procedure is done 36-40 hours after ovulation has been triggered.

Investigations required prior to insemination

Viral screening of the both partners: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).

Important instructions to follow on the day of the insemination

The partner must abstain from sexual intercourse for 2-5 days prior to the procedure.
The bladder must be full for the insemination procedure.

The insemination procedure
The intrauterine insemination is a painless procedure that does not require anaesthesia.
The personal information of the patient and partner is reviewed.
The patient will lie in gynaecological position, just like for a routine consultation.
A perineal drape is used to isolate the site and keep it sterile.
A metal speculum and sterile saline solution are used in order to clean the vagina of all its secretions.
With abdominal ultrasound guidance, a soft catheter is inserted through the cervix.
The semen sample of the partner/donor is then introduced through the catheter into the uterus.

Post-procedural treatment and recommendations
After the intervention, the vaginal progesterone treatment is supplemented; folic acid, vitamins, and minerals are also recommended.
Sexual intercourse is permitted in the evening after the procedure, after which sexual abstinence is advised.
The patient must avoid physical exertion, bathing in a tub, and bowel problems such as diarrhoea or constipation.
The patient is not advised to dye her hair.
Oceanic fish, sea food, and unpasteurised cheeses are not recommended.
In case of cramps, antispasmodic products can be administered.
Confirmation of success
The level of pregnancy hormone in the blood (βHCG) is tested 14 days after insemination.
In case of a positive βHCG result, the test is repeated after 48 hours.
Treatment must be continued diligently according to the exact recommendations of the doctor.
The ultrasound scan to confirm the pregnancy is scheduled 30-35 days after the transfer.

Interesting facts
The sex of the children conceived by means of intrauterine insemination is most often female because the spermatozoa carrying the X chromosome are heavier and, as such, they are more easily selected for insemination during the centrifuge process.

Embryo transfer

What is an embryo transfer?
The embryo transfer is a procedure by which one or two embryos either fresh or thawed are inserted in the uterus using ultrasound guidance.

Types of embryo transfer

FRESH transfer (abbreviated ET, from embryo transfer) refers to the transfer of embryos obtained from a fertilisation procedure undertaken during the same menstrual cycle.
FROZEN transfer (abbreviated FET, from frozen embryo transfer) refers to the transfer of embryos obtained from an in vitro fertilisation procedure undertaken during a previous menstrual cycle.

Getting ready for an embryo transfer
In case of a FRESH embryo transfer, after the ovarian drilling procedure, the patient is administered a prophylactic antibiotic and vaginal progesterone suppositories to prepare the endometrium.
If the transfer cannot be done immediately after the ovarian drilling (such as due to high risk of hyperstimulation syndrome or the presence of a polyp/hydrosalpinx), or if the couple already owns frozen embryos from a previous procedure, in order to perform a FROZEN embryo transfer (FET) it is necessary to first get the endometrium ready; this can be done either by triggering an artificial cycle with the help of oestradiol and progesterone, or on a normal menstrual cycle by using the body’s own hormones.

Getting ready for an FET
On day 1 of the menstrual cycle, the patient notifies the clinic about the onset of her menstruation and has an endovaginal ultrasound scan.
Din ziua 1 de ciclu menstrual se începe administrarea a 2 g de produs de estradiol de 3 ori pe zi, dimineața, prânz și seara.
From day 1 onwards, the patient takes 2g of oestradiol 3 times a day (in the morning, at lunch, and in the evening).
When the endometrium features favourable characteristics, the administration of vaginal progesterone suppositories begins.
On day 3 or day 5 of progesterone treatment, the thawed embryo is transferred.

Important instructions to follow on the day of the embryo transfer

The bladder must be full for the embryo transfer procedure.
The treatment with vaginal progesterone must be administered also on the day of the embryo transfer.

The embryo transfer procedure
The embryo transfer is a painless procedure that does not require anaesthesia.
The patient’s personal information is reviewed and the patient is shown the embryo under a microscope.
The patient will lie in gynaecological position, just like for a routine consultation.
A perineal drape is used to isolate the site and keep it sterile.
A metal speculum and sterile saline solution are used in order to clean the vagina of all its secretions and progesterone product.
With abdominal ultrasound guidance, a soft catheter is inserted through the cervix.
The embryo is then introduced through the catheter into the uterus.
The catheter is checked in case the embryo is still in it.

Post-procedural treatment and recommendations
After the intervention, the vaginal progesterone treatment is supplemented; folic acid, vitamins, and minerals are also recommended, as well as supporting the vascularisation of the uterus by administering a platelet antiaggregant and an anticoagulant.
The patient must avoid sexual intercourse, physical exertion, bathing in a tub, and bowel problems such as diarrhoea or constipation.
The patient is not advised to dye her hair.
Oceanic fish, sea food, and unpasteurised cheeses are not recommended.
In case of cramps, antispasmodic products can be administered.

Confirmation of success
The level of pregnancy hormone in the blood (βHCG) is tested 12 days after the transfer of a day 5 embryo or 14 days after the transfer of a day 3 embryo.
In case of a positive βHCG result, the test is repeated after 48 hours.
Treatment must be continued diligently according to the exact recommendations of the doctor.
The ultrasound scan to confirm the pregnancy is scheduled 30-35 days after the transfer.

Interesting facts
The rate of pregnancies obtained by means of frozen embryo transfer is similar to that of fresh transfers.
Not all the embryos can withstand the stress of the thawing process, but all the embryos that are selected for freezing must be of good quality.
Frozen embryos can last up to 10 years if stored in liquid nitrogen at a temperature of -180˚C.

The curettage

What is a curettage?
The curettage is an invasive procedure by which a curette is inserted in the uterine cavity and used to scrape the walls of the uterus aiming to collect samples for a biopsy of the endometrium or to evacuate the contents of an arrested pregnancy.

Types of curettage

The biopsy curettage - recommended to patients diagnosed with endometrial hypertrophy (thickening of the endometrium) or dysfunctional haemorrhage
The evacuation and biopsy curettage - recommended for the evacuation of arrested pregnancies, incomplete abortions, and anembryonic pregnancies.

The indications of curettage

Endometrial hypertrophy
Endometrial hyperplasia
Dysfunctional haemorrhage
Polypoid endometrium
Suspicion of endometrial neoplastic pathology
Arrested pregnancy
Anembryonic pregnancy (or blighted ovum)
Leftover trophoblastic material after an incomplete abortion

The contraindications of curettage

Untreated vaginal infections
Papanicolau smear test results not available/abnormal

Is anaesthesia necessary?
Yes, it is! The curettage procedure first requires the painful manoeuvring of the cervix with the help of cervical dilators. Anaesthesia is necessary in order to help the patient relax and avoid pain.

Scheduling a curettage
In case of arrested pregnancy, the curettage is necessary if the medication-induced therapeutic abortion is not possible or there is significant genital bleeding.
In case of gynaecological pathology, a curettage may be done to achieve haemostasis, either during bleeding or scheduled in the first part of the menstrual cycle, after the period of menstrual bleeding.

Investigations required prior to a curettage:

Routine tests: Complete blood count, AST, ALT, urea, creatinine, uric acid, glycemia.
Coagulation tests: Fibrinogen test, aPTT.
Viral screening of the female partner: HbaAg, anti-HBc, HIV 1 and 2, RPR, anti-HCV.
The Papanicolau smear test and vaginal wet tests (Chlamydia, Mycoplasma, Ureaplasma, vaginal secretions).
Blood type and Rh test, so that Rh-negative and Rh-incompatible patients (Rh-positive partner) may be administered anti-D immunoglobulin
Cardiology consultation for patients older than 45 or diagnosed with cardiovascular conditions

Important instructions to follow on the day of the curettage

The bladder must be emptied for the procedure.
Because the procedure is done under general anaesthesia, the patient should not eat or drink on the day of the intervention.

Chiuretajul uterin propriu-zis
The patient will lie in gynaecological position, just like for a routine consultation.
A sterile perineal drape is used to isolate the site and the vulvovaginal and exocervical areas are cleansed with betadine.
Two-bladed specula are used to gain access to the vagina and then the anterior lip of the cervix is gripped with a tenaculum. The cervical canal is gradually dilated with Hegar dilators so that the curette may be inserted in the uterus. The inner walls of the uterine cavity are scraped, and the resulting material is removed; samples are sent for anatomopathological analysis.

Post-procedural treatment and recommendations
Prophylactic antibiotic treatment is necessary both during and after the procedure
The patient is recommended to rest, to abstain from sexual activity for 7 days, and to present for an ultrasound scan 1 month after the procedure; also, effective contraception methods are needed for a period of 2-3 months.
The anatomopathological results take about 7-14 days.

Interesting facts
The curettage is a surgical intervention that must be carried out very gently, because if it is too abrasive it can lead to the formation of synechiae (adhesions of adjacent parts of the uterine wall).
The most severe form of synechiae, called Asherman’s syndrome, impedes pregnancy by reducing the size of the uterine cavity and hindering communication with the fallopian tubes.

Fertility Preservation

An increasing number of women choose to delay having children after the age of 30. This trend can be seen across Europe, and it has also been confirmed in Romania where, according to the National Institute of Statistics, the number of women who choose to have their first baby after the age of 35 has doubled over the last quarter of a century.

Unfortunately, the fertile potential of women decreases significantly with age because the number of oocytes (the female sexual cells) and their quality diminish year after year, resulting in lower chances of fertilisation and normal embryo development.

Fertility can be assessed gynaecologically and by analysing certain hormone markers. The anti-Mullerian hormone (AMH) points to the woman’s ovarian reserve.

Analysing the AMH level provides a range of useful information:

it can help predict the onset of menopause
it is a prediction factor for obtaining a pregnancy by means of assisted human reproduction techniques
it is a predictor for the patient’s response to controlled ovarian stimulation in IVF procedures
it is a prediction factor for ovarian hyperstimulation syndrome after controlled ovarian stimulation
it points to the degree of damage to an ovary after surgery on it or chemotherapy

Preserving female fertility consists in freezing oocytes to be used for obtaining a pregnancy at a later date. The oocytes are frozen in liquid nitrogen at a temperature of -196 degrees Celsius, and they are safely stored until the patient decides to use them. The oocyte bank is constantly supplied with liquid nitrogen in order to maintain optimal storage conditions. Vitrification at a temperature of -196 degrees Celsius is done almost instantaneously to avoid the formation of ice crystals inside the oocyte, such as may happen during slow conventional freezing. In this way, the quality of the frozen oocytes is not affected.

There are two categories of patients for whom fertility preservation is a recommended approach:

Women who opt for social freezing, which means fertility preservation for social reasons, ideally before the age of 35, so that a sufficient number of high quality oocytes can be harvested and stored until the woman is ready for a pregnancy.
Women who are diagnosed with certain medical conditions and who plan to undergo treatments which could impair their fertility (such as radio-chemotherapy for various neoplasms, primary ovarian insufficiency, stage IV endometriosis) can choose to have sexual cells harvested and frozen before starting the treatment and risking the depletion of their ovarian reserve.

The oocytes are collected by means of echo-guided ovarian drilling after the ovaries have been stimulated with hormones according to a tailored protocol established by the clinician. If hormone-controlled ovarian stimulation is contraindicated, the oocytes may be harvested in the process of a normal menstrual cycle. Ovarian drilling is done under anaesthesia, and the collected oocytes are prepared for freezing and then vitrified in liquid nitrogen.

Infertility treatments