Possible causes of female infertility
- Reduced ovarian reserve and hormonal dysfunction of folliculogenesis and ovulation
- Tubal pathologies (anatomical and functional)
- Endometriosis
- Acute or chronic pelvic infections
- Immunological problems
- Chromosomal abnormalities
- Lifestyle
Possible causes of male infertility
- Genito-urinary infections
- Varicocele
- Dysfunctions in sperm production, emission and/or function
- Viral diseases that can cause orchitis (chickenpox, measles, mumps)
- Chromosomal anomalies (Klinefelter syndrome, gonadal dysgenes, cystic fibrosis)
- Lifestyle (alcohol, smoking, drugs, drugs, risky jobs)
Idiopathic or unexplained infertility occurs when, despite all diagnostic investigations performed, the cause of infertility has not been identified
The typical diagnostic phase in women includes tests such as:
Vaginal and cervical swab: It makes it possible to assess the presence of genital infections that may have a negative influence on fertility.
Transvaginal pelvic ultrasound: It allows the detection of uterine malformations, fibroids, endometrial polyps, ovarian changes (cysts of various kinds, micropolicystosis, etc.).
Hormone dosages: They are performed by taking blood samples on certain days of the menstrual cycle and make it possible to monitor ovulation or possible hormonal imbalances e.g. hyperprolactinemia, polycystic ovary syndrome, premature ovarian exhaustion, etc.
Hysterosalpingography: Radiological investigation (X-ray), which allows the assessment of the uterine cavity and tu baric patency using a radio-opaque contrast medium that is injected through a special catheter through the cervical canal into the uterus and then into the tubes.
Sonohysterosalpingography: Transvaginal ultrasound investigation that allows assessment of the uterine cavity and tubal patency using saline solution injected through a special catheter through the cervical canal
Hysteroscopy: It allows direct fibre-optic visualisation of the cervical canal, uterine cavity and tubal ostia for the study of uterine malformations, endometrial polyps, submucosal fibroids, etc.
Laparoscopy: It allows direct visualisation of the pelvis by introducing an optical system into the abdominal cavity. Laparoscopy is indicated in unexplained infertility, in cases of dubious hysterosalpingography, in endometriosis, in the evaluation of the ovaries, and in the outcomes of pelvic inflammatory disease.
Karyotype: This investigation assesses the presence of a normal chromosome set in the patient (woman 46XX, man 46XY). It is performed by taking a blood sample.
The male diagnostic phase includes tests such as:
Spermiogram with capacitation test: It is one of the fundamental tests for the study of infertile couples as it provides the first indications of the fertilising capacity of spermatozoa and allows further investigations to be directed towards identifying the cause of infertility. Semen must be collected by masturbation in a sterile container, taking hygienic precautions to avoid contamination by microorganisms. The ideal period of sexual abstinence before production is 3-5 days.
Spermioculture and urethral swab: This examination is indicated in the event of indirect signs of infection revealed by the spermiogram. It makes it possible to identify the pathogenic germ responsible and thus to implement appropriate medical therapy.
Hormone dosing: It is carried out by taking a blood sample and assesses hormone levels, which if altered can affect sperm production.
Scrotal ultrasound and sperm vessel Doppler: It allows visualisation of the testicular parenchyma in the evaluation of the presence of any structural changes in the testicles and other structures of the scrotal bursa (e.g. varicocele).
Transrectal ultrasound: It allows visualisation of the prostate, seminal vesicles and ejaculatory ducts in cases of suspected obstruction of the seminal tract.
Search for Y chromosome microdeletions: in some cases of severe male infertility, it may be necessary to perform such an examination (blood sample), which consists of assessing the possible absence of certain points of the Y chromosome (male chromosome) as a genetic cause of infertility.
Karyotype: This investigation assesses the presence of a normal chromosome set in the patient (woman 46XX, man 46XY). It is performed on a blood sample.
Cystic Fibrosis (CF) gene mutation search: In the general population, a person (woman or man) may be a carrier of a mutation in the cystic fibrosis gene. The union of two healthy carriers of the same cystic fibrosis gene mutation can result in a fetus with cystic fibrosis. In a particular group of azoospermic patients (complete absence of spermatozoa in the ejaculate) with congenital agenesis of the vas deferens, the risk of Cystic Fibrosis gene mutations is greatly increased compared to the general population.
The various diagnostic tests, as always in medicine, will then be dictated by the specific medical history of each couple.
The therapeutic approach
Regarding, very generally, the therapeutic approach, we can speak of:
Multiple follicular growth induction therapy
All assisted reproduction techniques involve an initial phase of pharmacological ovarian stimulation in order to obtain an adequate number of oocytes for the technique. The response to the drug is individual and sometimes unpredictable and varies depending on the drug, the dosage established, the age and clinical characteristics of the patient. The monitoring of follicular growth is aimed at obtaining optimal development of mature follicles in adequate numbers for the PMA technique and at limiting as far as possible the occurrence of pathological conditions that are risky for the patient (ovarian hyperstimulation syndrome).
During monitoring, therapy may be modified according to individual ovarian response. In case of inadequate ovarian response, risk of ovarian hyperstimulation or other clinical conditions the cycle may be suspended. Based on ultrasound monitoring (and possible hormone dosing) when optimal development of mature follicles in adequate numbers for the technique has been achieved, the doctor prescribes administration of chorionic gonadotropin 'hCG', which induces final maturation of the oocytes contained in the follicles.
Intrauterine Insemination (I.U.I.)
It is a Level I medically assisted procreation procedure based on the deposition of spermatozoa directly inside the uterine cavity. This procedure is carried out after ovulation induction.
The indications for this method are:
parameters of mild oligo-asthenospermia (moderate reduction in the number, motility and normal shape of spermatozoa) in the male partner;
absence of tubal alterations;
absence or minimal presence of endometriosis;
cervical factor infertility: organic, functional, immunological (e.g. mucus obstruction at the cervix);
all conditions of unexplained infertility in which the presence of tubal and/or uterine and seminal fluid alterations has been excluded;
repeated failures of pregnancy induction with ovulation stimulation and targeted intercourse.
F.I.V.E.T.: In Vitro Fertilisation and In utero Embryo Transfer I.C.S.I.: IntraCytoplasmic Sperm Injection
IVF technique indications: tubal factor, moderate male infertility, endometriosis, unexplained infertility with repeated failures of intrauterine insemination cycles. - The oocytes and sperm are placed in contact in the laboratory for approximately 16-18 hours. The fertilisation of the oocyte takes place in vitro without intervention by the operators. The resulting embryos are then transferred into the uterus. ICSI technique indications: severe or severe male infertility, failure to fertilise from previous IVF cycles, repeated implantation failures. This technique involves the insertion (microinjection) by the biologist of a single spermatozoon selected on the basis of the best morphological and motility characteristics inside the mature oocyte. The resulting embryos are then transferred into the uterus.
The success of these techniques is highly dependent on numerous characteristics, including the age of the partners, the cause and duration of infertility, the specific ovarian reserve of the patient, the treatment performed, the specific performance of the laboratory, the experience of the operator, the goodness of the embryo transfer, etc. Thus indicating that, contrary to popular belief, PMA procedures and their performance are far from standardised.
Medically assisted procreation:
NEW TECHNOLOGIES
In the field of Reproductive Medicine, it is essential to offer patients the knowledge and thus theuse of the latest technologies which, to date, we have at our disposal. These are fundamental for achieving increasingly satisfactory results.
Among the new technologies is the Time-lapse Embryo Imagingan innovative tool that enables images of the embryo coming to life following fertilisation of the oocyte. This advanced technology allows the continuous taking of photographs of the embryo, enabling the visualisation of the complete sequence of its evolution before its transfer into the woman's uterine cavity. Images are taken by means of a camera directly from inside the incubator, keeping the embryo safe. In this way, the future parents have the opportunity to experience every single emotionally-charged phase of the embryo's first hours of life. Continuous observation of the evolution of the fertilised egg cell also provides us with information on the normality of the evolutionary process and the exact moment when the embryo reaches such maturity that it can no longer live outside the body of its future mother, but must be transferred. Through research we also investigate the potential future applications this technique might have, such as the possibility of contributing to improve pregnancy chances.
Couples undergoing PMA can now obtain information on the health status of embryos produced in the laboratory. This is why we can make use of laboratory techniques that allow us to study the DNA of oocytes or embryos to understand whether the embryo could potentially be affected by chromosomal abnormalities. The procedures for obtaining such information are the Preimplantation Genetic Diagnosis (PGD=PGT-M) for couples at risk of transmitting genetic diseases and the Preimplantation Genetic Screening (PGS=PGT-A) which carries out an analysis of embryos from healthy couples in order to detect abnormal chromosome numbers (aneuploidies) prior to transfer.
Chromosomal alterations concerning both the number and structure of chromosomes can be detected using the PGT-A technique (pre-implantation genetic testing for aneuploidy). After in vitro fertilisation and before its transfer into the uterus, the embryo's genetic material is studied to detect possible genetic alterations. A biopsy of each embryo and those with an abnormal number of chromosomes are discarded. Aneuploidy is a fairly common cause of premature termination of pregnancy, and the use of PGT-A reduces the risk rate and is indicated for patients at risk of having a child with chromosomal abnormalities due to advanced maternal age, patients who already have a history of termination of pregnancy or who have had in-vitro fertilisation failures. Therefore, the chance of conceiving a child with chromosomal defects can be significantly reduced by performing PGT-A screening. The advantages of using this technique are increased implantation rates, reduced abortion rates and reduced twin pregnancy rates.
The PGT-M technique (pre-implantation genetic testing for monogenic diseases) searches for the genetic alteration affecting a particular gene, thus preventing the transmission of diseases such as cystic fibrosis, thalassaemia or muscular dystrophy. Today it is used for more than 400 different conditions including those with late development, mitochondrial disorders and by HLA typing. This technique makes use of two different diagnostic methods, a pre-implantation genetic one for oocytes, which analyses a specific part of the egg and is therefore only able to detect hereditary diseases of maternal origin, and a pre-implantation one on embryos. The cells taken are treated to study their genetic material and to find out whether the embryo has been affected by a hereditary disease. Once the analysis of each of the embryos has been completed, those that do not have the disease are chosen and transferred into the woman's uterus. It is essential for the couple to take advantage of the presence, support and professionalism of a good staff consisting of a geneticist, psychologist, gynaecologist and embryologist in order to achieve the most advantageous results.
Our achievements in PMA
Several factors determine success in in vitro procreation, the main ones being:
- The stimulation protocol employed
- The operator's experience in performing oocyte retrieval
- The laboratory's experience in performing inseminations and embryo/blastocyst cultures
- The quality of the embryos obtained
- Experience in performing embryo transfer
- The receptivity of the endometrium
Contrary to what one might think, the effectiveness of in vitro fertilisation depends very much on the experience of the practitioners involved (doctors and embryologists). Just as the efficacy of all medical-surgical services is highly dependent on the technical ability and training of the doctor-surgeon delivering them.
Given the same biological characteristics of the couple, the stimulation protocol, the dosage of the drugs, the timing of the pick-up and the operator's experience may alter the number of mature oocytes available to the couple, thus having a great impact on the number of embryos available at the end of the procedure.
The experience of embryologists and the adequacy of laboratory equipment will impact fertilisation rates and thus the number and quality of embryos/blastocysts available to the couple
The choice of timing for embryo transfer and the skill of the doctor in this delicate procedure then have a strong impact on the success rate.
Endometrial receptivity obviously plays a key role. Today, there is the possibility through ultrasound and hormone dosage to have indications on the state of endometrial receptivity and therefore also for this aspect, the clinician's experience plays a key role.
This is to say that in vitro fertilisation success rates are NOT constant and equal everywhere but depend on the centre where the cycle is performed and the doctor performing the procedure
Intrauterine insemination and in vitro fertilisation: what is the difference?
Intrauterine insemination is a technique called I level. It is only applied in couples selected by age, who do not present severe male infertility and/or tubal infertility. The success rate is lower than with level II techniques, as we have no control over the process, but intrauterine insemination has less technological invasiveness (fertilisation occurs spontaneously "in-vivo") and less pharmacological invasion (only mild ovarian stimulation is required).
In vitro fertilisation (II level) plans to recreate "in-vitro" all the processes leading to the union of the gametes; therefore, it is necessary to have both the oocyte and the spermatozoon in the laboratory and to carry out fertilisation in a test tube. This type of approach greatly increases success rates (in the case of the IVF ranges from 38.2% to almost 80% depending on the number of cycles) because: the quality of the gametes (oocytes and spermatozoa) is checked by choosing the most suitable for generating embryos, fertilisation is ensured, and the quality of the embryos obtained is assessed before they are transferred to the uterus.
What are success rates?
The achievement of pregnancy is typically assessed at two levels:
- Positive pregnancy test (betahCG +)
This is the first sign of a pregnancy, a reflection of the result of the treatment, and indicates the implantation of the embryo in the uterus, usually 14 days after the transfer. From this moment on, nature will take its course, as in any other pregnancy, whatever its origin. - Clinical pregnancy
A clinical pregnancy occurs when pregnancy is ascertained by ultrasound, through visualisation of the gestational chamber, usually 6-7 weeks after the embryo has been transferred into the uterus.
Our results are reported in terms of positive pregnancy tests compared to the number of embryo transfers performed.
The success of the PMA procedure cannot, in any case, disregard the protection of the health of the woman and the unborn child: the clinical strategies adopted must therefore be aimed not only at achieving pregnancy, but also at reducing the risk of miscarriage and multiple pregnancy, or, more generally, reducing the obstetrical risk of pregnancy.
Success rates of Intrauterine InseminationÂ
Artificial insemination is the treatment of least complexity, and is usually performed until the patient is 35-37 years old. This treatment offers good cumulative rates up to the third attempt.
The success rate of each cycle is always the same. Going from the first to the second and finally to the third cycle increases the cumulative percentage, i.e. the percentage of patients who overall achieved pregnancy over the three treatments increases.
In Vitro Fertilisation success ratesÂ
In IVF, success rates are higher than in IUI. This is to be expected, since in in vitro fertilisation the aim is to transfer the embryos into the uterus, thus bringing the patient as close as possible to the point of initiation of pregnancy
The success rate changes in the various couples according to the biological characteristics of both partners, but certainly the woman's age remains the most impactful variable. And that is why success rates are reported according to certain age groups of the woman.
In terms of treatment success, the number of embryos obtained from a single ovarian stimulation cycle is also very relevant. After embryo transfer following oocyte retrieval, supernumerary embryos are frozen. If pregnancy is not achieved after the first transfer, another transfer can then be carried out immediately without having to repeat ovarian stimulation and oocyte retrieval.
As the number of available embryos increases, there will therefore be an increase in the cumulative success rate.
