Fertility problems constitute a serious medical, social, and demographic problem ^[1][2][1,2]. The World Health Organization defines infertility as a failure to achieve pregnancy after 12 months or more of regular unprotected sexual intercourse (2–4 times a week) ^[3][4][3,4]. Due to ever-growing infertility rates, which presently concern 10–16% of couples worldwide, including about one million in Poland [5], according to the Polish Society of Reproductive Medicine and Embryology (PTMRiE) and the Fertility and Sterility Special Interest Group of the Polish Society of Gynecologists and Obstetrics (SPiN PTGiP), it is recommended that patients who are under 35 years old begin diagnosis and infertility treatment after a year of unsuccessful attempts at becoming pregnant. For women aged 35–40 years, diagnosis and therapy should be considered 6 months after unsuccessful attempts at pregnancy, whereas after 40, as early as directly after a declaration of procreation is made ^[6][7][6,7]. Infertility is defined as a failure to achieve a pregnancy after 1 year of regular monthly sexual intercourse with the aim of reproduction (2–4 times a week) and without the use of any contraceptive measures. Involuntary childlessness is a problem that concerns a high percentage of the population. It is estimated that this phenomenon affects as high as 20% of couples globally; in Poland, the problem of infertility affects approximately one million couples ^[3][4][3,4]. Recently, there has been an increase in the number of couples seeking aid in enlarging their family, which is most likely connected to better access to specialist treatment, modern diagnosis, society becoming richer, and an increase in social awareness [8]. An increasingly common problem with becoming pregnant can also be connected with observed sociocultural changes, which have resulted in the postponement of decisions about maternity until later in life [1], at which point it can be difficult for therapy to be effective and to obtain an adequate reason for this with regard to the treatment used [2]. It is often women who initially decide to seek help in connection with childlessness, agreeing to diagnosis and the commencement of therapy. On the other hand, among men, the dominant approach to the problem of infertility is skepticism because they believe that the only cause of the discussed problem is their partner, and they are negatively predisposed to discuss their own fertility with a specialist. Such a situation is described as the “theft of the woman’s reproductive time” [5] because with increasing age, there are unbeneficial changes in the activity of ovaries and quality of egg cells, in addition to the occurrence of dysfunctions in fissuration processes and an increase in the percentage of spontaneous miscarriages. In men, with increasing age, there are also changes in the hormone concentration profile, including a decrease in the concentration of testosterone with a simultaneous increase in the concentration of testosterone binding protein; however, this connection has not been fully explained to date ^{[9][10][11][12]}[9,10,11,12].

The term assisted reproduction technology (ART) was introduced in the 1970s. It covers all methods that are used to assist in a successful pregnancy, where ART techniques are used to replace the biological functions connected with procreation. The Polish Society of Reproductive Medicine and Embryology (PTMRiE) and the Polish Society of Gynecologists and Obstetrics (PTGiP) recommend further optimization of ART techniques ^[6][7][13][6,7,13].

Intrauterine inseminations (artificial insemination) are classified as in vivo methods of introducing semen either of a husband/partner (AIH, artificial insemination by husband) [6] or a donor (AID, artificial insemination by donor) [14] or its components into a woman’s birth canal after laboratory preparation [15].

Insemination is conducted in a natural cycle or after ovulation stimulation, which increases the success rate of the procedure. However, it must be stated that, per recommendations of the PTGP, stimulation is only recommended if no more than three pre-ovulation ovarian follicles are present. The highest effectiveness is observed within three attempts of intrauterine insemination ^[16][17][16,17].

Among the methods available for treating infertility, regardless of its cause, in vitro fertilization is characterized by having the greatest efficiency. Prior to the procedure, a man must conduct a karyotype test and be subject to analysis for microdeletions of the AZF region on the Y chromosome. In the case of women, it is recommended that the ovarian reserve be evaluated to allow for selection of the best possible method for ovary hyperstimulation ^[18][19][18,19].

The process of in vitro fertilization (IVF) can be conducted under in vitro conditions using the classic method, which is based on the introduction of previously prepared sperm cells into egg cells or on a technique of sperm cell microinjection into an egg cell that is selected randomly (ICSI, intracytoplasmic sperm injection) or morphologically (IMSI, intracytoplasmic morphologically selected sperm injection). This method is recommended in infertility connected with the male factor [20].

The choice of the appropriate strategy of ovarian hyperstimulation allows for the growth of many ovarian follicles and, subsequently, for the collection of many mature egg cells. Oocytes obtained as a result of puncture conducted under the control of ultrasound are subject to a further process of fertilization under the conditions of an embryologic laboratory. Then, an intrauterine transfer of one to two embryos is performed after an incubation period of 2–6 days [6].

In order to cause the hyperstimulation of ovaries, drugs that belong to the group of gonadotropin-releasing hormone analogs (short or long protocol) or gonadotropin-releasing hormones (GnRH) are used ^[21][22][21,22].

A critical point in determining the effectiveness of in vitro fertilization is embryo transfer, meaning the transfer of the embryo into the uterus and minimization of the risk of incidence of luteal phase defects [18].

The principal recommendations for IUI and in vitro fertilization are summarized in Table 1.

Intrauterine inseminations	In vitro fertilization
Semen liquefaction dysfunctions	Irreversible fallopian tube damage
Ejaculation dysfunctions (including retrograde ejaculation)	Lack of fallopian tubes
Problems with intercourse	Endometriosis of the III or IV stages with a severity level of moderate to serious
Cervical factor	Abnormal semen in the form of severe oligoasthenoteratozoospermia or azoospermia with normal spermatogenesis
Using donor semen due to male factor infertility	Ineffective pharmacological or surgical treatment in couples with moderate male factor, idiopathic infertility, fallopian tube factor, or ovulatory dysfunctions
	Fertile couples diagnosed with recessive genetic changes for both partners, which are connected with the incidence of irreversible defects or disease in the offspring, or were diagnosed with a viral disease or encouraged to postpone fertility due to medical recommendations

Prenatal diagnosis includes all tests that may be performed prior to the birth of the child and is a significant achievement in the field of contemporary perinatology. The dynamic development of prenatal diagnosis has been observed within the last 20 years, which is connected with the popularization of techniques of fetal ultrasound imaging (USG), as well as progress in the fields of biochemistry, immunology, immunogenetics, cytogenetics, and molecular biology. Intrauterine fetal imaging creates the possibility of early detection of most developmental defects, which translates to an increase in the success rate of intrauterine treatment or surgical intervention directly after birth. Apart from that, an increase in the survival rate or complete recovery of fetuses with a congenital defect is possible thanks to specialist, comprehensive care facilities of the highest referral level ^[27][28][27,28].

Methods of prenatal diagnosis can be categorized as non-invasive or invasive. The first group includes fetal ultrasound; biochemical testing of the blood sampled from pregnant women for the presence of markers, such as free beta-subunit human chorionic gonadotropin, pregnancy-associated plasma protein A, and a-fetoprotein (AFP); and cell-free DNA testing. On the other hand, invasive testing includes trophoblast biopsy, amniopunction, cordocentesis, and fetoscopy [29].

The principal goal of prenatal diagnosis is to detect all kinds of pathologies in the development of the fetus, as well as irregularities of a genetic nature. It has been confirmed that as the mother’s age increases, the risk of a child being burdened with a genetic and/or congenital development defect also increases. However, it must be understood that the mother’s age is not the only factor that increases the risk of the incidence and development of fetal defects ^[7][30][7,30].

Given the above, the Fetal Medicine Foundation has developed guidelines for prenatal diagnosis in the first trimester of pregnancy based not only on the mother’s age but also on markers of chromosomal aberrations in fetuses ^[7][31][7,31]. One of the newest indicators used to evaluate the risk of incidence of development of defects in fetuses is the marking of cell-free DNA in the blood of pregnant women. This method is characterized by a detection rate of more than 99% with regard to the most commonly occurring trisomy, also showing a low percentage of false-positive results.

The source of free-cell DNA is the placenta, and its detection is possible as early as the fourth week of pregnancy [32]. The fetal genetic material that can be detected in the mother’s blood constitutes 3–6% of the entire extracellular DNA in the mother’s bloodstream. The biological material for analysis is full blood collected from the pregnant woman, from which DNA is then extracted. Due to the fact that until now, no method of complete separation of a mother’s DNA from fetal DNA has been developed, the evaluation is based on the confirmation or exclusion of the nucleotide sequence of genes that are not present in the mother’s blood, e.g., RHD, SRY, and DYS14, with the use of qPCR ^[32][33][32,33].